1. Seagen Inc. (NASDAQ:SGEN) will host a conference call and webcast on Tuesday, September 21, 2021 to discuss the U.S. Food and Drug Administration approval of TIVDAK™ (tisotumab vedotin-tftv). Access to the event can be obtained as follows:

    September 21, 2021

    6:00 a.m. Pacific Time / 9:00 a.m. Eastern Time

    • Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10160278
    • Webcast with slides will be available at www.seagen.com in the Investors section. A webcast replay will be archived on the Company's website.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered…

    Seagen Inc. (NASDAQ:SGEN) will host a conference call and webcast on Tuesday, September 21, 2021 to discuss the U.S. Food and Drug Administration approval of TIVDAK™ (tisotumab vedotin-tftv). Access to the event can be obtained as follows:

    September 21, 2021

    6:00 a.m. Pacific Time / 9:00 a.m. Eastern Time

    • Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10160278
    • Webcast with slides will be available at www.seagen.com in the Investors section. A webcast replay will be archived on the Company's website.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

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    • TIVDAK is a First-in-Class Antibody-Drug Conjugate Directed to Tissue Factor, a Protein Expressed on Cervical Cancer Cells
    • New Monotherapy Approved for Use in a Cancer with Limited Treatment Options

    COPENHAGEN, Denmark, and BOTHELL, Wash.; September 20, 2021 Genmab A/S (NASDAQ:GMAB) and Seagen Inc. (NASDAQ:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to TIVDAKTM (tisotumab vedotin-tftv), the first and only approved antibody-drug conjugate (ADC) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is approved under the FDA's Accelerated Approval Program based on tumor response and the durability of the…

    • TIVDAK is a First-in-Class Antibody-Drug Conjugate Directed to Tissue Factor, a Protein Expressed on Cervical Cancer Cells
    • New Monotherapy Approved for Use in a Cancer with Limited Treatment Options

    COPENHAGEN, Denmark, and BOTHELL, Wash.; September 20, 2021 Genmab A/S (NASDAQ:GMAB) and Seagen Inc. (NASDAQ:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to TIVDAKTM (tisotumab vedotin-tftv), the first and only approved antibody-drug conjugate (ADC) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is approved under the FDA's Accelerated Approval Program based on tumor response and the durability of the response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.1

    "Once recurrent or metastatic cervical cancer progresses, there is a need for more options for these patients," said Robert L. Coleman, M.D., Chief Scientific Officer, US Oncology Research and lead investigator of the innovaTV 204 clinical trial. "This is an important development for patients with recurrent or metastatic cervical cancer."

    In the innovaTV 204 clinical trial, TIVDAK was evaluated in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Results from the trial showed a 24 percent confirmed objective response rate (ORR) (95% CI; 15.9-33.3), as assessed by an independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The median duration of response (DOR) was 8.3 months (95% CI; 4.2 to not reached).

    The prescribing information for TIVDAK includes a BOXED WARNING for ocular toxicity, and Warnings for peripheral neuropathy, hemorrhage, pneumonitis, and embryo-fetal toxicity. The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), peripheral neuropathy (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%). Please see Important Safety Information below.1

    "We are thrilled to see this new treatment approved by the FDA. We are grateful to have another option for this devastating disease," said Tamika Felder, Founder, Cervivor. 

    "TIVDAK's approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "The journey towards the approval of TIVDAK started nearly two decades ago with innovative research by scientists at Genmab and Seagen and reflects on our purpose of making an impact in the lives of cancer patients and their families. Today's announcement marks Genmab's evolution into a fully integrated biotechnology company and we would like to thank patients, caregivers, investigators and our collaborators for their participation in our clinical studies."

    "We are pleased with the accelerated approval of TIVDAK, Seagen's third FDA-approved antibody-drug conjugate, and fourth approved medicine. Our mission at Seagen is to develop medicines that make a difference for people impacted by cancer," said Roger Dansey, M.D., Chief Medical Officer, Seagen.

    The Biologics License Application (BLA) for TIVDAK was submitted in February 2021 and accepted with Priority Review in April 2021. The submission was based on the results of the innovaTV 204 trial.

    The FDA's Accelerated Approval Program allows for approval of a medicine based on a surrogate endpoint that is reasonably likely to predict clinical benefit, if the medicine fills an unmet medical need for a serious condition. A global, randomized phase 3 clinical trial (innovaTV 301) is underway and is also intended to support global registrations.

    About Cervical Cancer

    It is estimated that in 2021, more than 14,480 new cases of invasive cervical cancer will be diagnosed in the U.S., and 4,290 women will die from the disease.2 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying of the disease in 2018.3

    About the innovaTV 204 Trial

    The innovaTV 204 trial (NCT03438396/GOG-3023/ENGOT-cx6) is an open-label, multicenter, single-arm Phase 2 trial that evaluated tisotumab vedotin in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Patients were excluded if they had active ocular surface disease, any prior episode of cicatricial conjunctivitis or Stevens-Johnson syndrome, Grade ≥2 peripheral neuropathy or known coagulation defects leading to an increased risk of bleeding. The main efficacy outcome measures were confirmed ORR per RECIST v1.1 as assessed by an IRC and DOR.1

    The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the GOG Foundation, Inc. (GOG). For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

    About TIVDAK (tisotumab vedotin-tftv)

    TIVDAK (tisotumab vedotin-tftv) is an ADC composed of Genmab's human monoclonal antibody directed to tissue factor (TF) and Seagen's ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of TIVDAK is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, TIVDAK also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.1

    TIVDAK (tisotumab vedotin-tftv) for injection, for intravenous use, 40 mg Important Safety Information

    BOXED WARNING: OCULAR TOXICITY

    TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

    Warnings and Precautions

    Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8% of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose.

    In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse, including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

    Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

    Peripheral neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barré syndrome.

    Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

    Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3      hemorrhage occurred in 5% of patients.

    Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

    Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

    Monitor patients for pulmonary symptoms indicative of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

    Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

    Embryo-fetal toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%) pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

    Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK;       the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

    The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

    Drug interactions

    Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

    Use in Specific Populations

    Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

    Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

    Please see full prescribing information, including BOXED WARNING for TIVDAK here.

    About Genmab

    Genmab is an international biotechnology company with a core purpose to improve the lives of people with cancer. For more than 20 years, Genmab's vision to transform cancer treatment has driven its passionate, innovative and collaborative teams to invent next-generation antibody technology platforms and leverage translational research and data sciences, fueling multiple differentiated cancer treatments that make an impact on people's lives. To develop and deliver novel therapies to patients, Genmab has formed 20+ strategic partnerships with biotechnology and pharmaceutical companies. Genmab's proprietary pipeline includes bispecific T-cell engagers, next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates.

    Genmab is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About the Seagen and Genmab Collaboration

    Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.

    Genmab A/S Contacts:

    For Media:        

    Marisol Peron, Senior Vice President, Global Investor Relations & Communications

    T: +1 609 524 0065; E: mmp@genmab.com

    For Investor Relations:

    Andrew Carlsen, Vice President, Head of Investor Relations

    T: +45 3377 9558; E: acn@genmab.com



    Seagen Contacts:

    For Media:

    David Caouette

    Vice President, Corporate Communications

    (310) 430-3476

    dcaouette@seagen.com

    For Investor Relations:

    Peggy Pinkston

    Senior Vice President, Investor Relations

    (425) 527-4160

    ppinkston@seagen.com

    Genmab Forward Looking Statements

    This Company Announcement contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab's most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab's most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

    Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo. TIVDAKTM and the TIVDAK logo are trademarks owned by Seagen Inc.

    Seagen Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the continued FDA approval of TIVDAK (tisotumab vedotin-tftv) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy; the conduct of an ongoing randomized phase 3 clinical trial (innovaTV 301) intended to verify the clinical benefit of TIVDAK and support global registrations; and the therapeutic potential of TIVDAK, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that innovaTV 301 and subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; that utilization and adoption of TIVDAK by prescribing physicians may be limited by the availability and extent of reimbursement and other factors; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    1 TIVDAK [package insert]. Bothell, WA: Seagen, Inc.

    2 Cancer Stat Facts: Cervical Cancer. National Cancer Institute website. https://seer.cancer.gov/statfacts/html/cervix.html. Accessed September 16, 2021.

    3 Bray F, Ferlay J, Soerjomataram I, et al. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2018;0: 1-31.

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  2. - TIVDAK is a First-in-Class Antibody-Drug Conjugate Directed to Tissue Factor, a Protein Expressed on Cervical Cancer Cells -

    - New Monotherapy Approved for Use in a Cancer with Limited Treatment Options -

    Seagen Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to TIVDAK™ (tisotumab vedotin-tftv), the first and only approved antibody-drug conjugate (ADC) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is approved under the FDA's Accelerated Approval Program based on tumor response and the durability of the response. Continued approval may be contingent…

    - TIVDAK is a First-in-Class Antibody-Drug Conjugate Directed to Tissue Factor, a Protein Expressed on Cervical Cancer Cells -

    - New Monotherapy Approved for Use in a Cancer with Limited Treatment Options -

    Seagen Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to TIVDAK™ (tisotumab vedotin-tftv), the first and only approved antibody-drug conjugate (ADC) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is approved under the FDA's Accelerated Approval Program based on tumor response and the durability of the response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.1

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210920005921/en/

    40 mg vial and carton (Photo: Business Wire)

    40 mg vial and carton (Photo: Business Wire)

    "Once recurrent or metastatic cervical cancer progresses, there is a need for more options for these patients," said Robert L. Coleman, M.D., Chief Scientific Officer, US Oncology Research and lead investigator of the innovaTV 204 clinical trial. "This is an important development for patients with recurrent or metastatic cervical cancer."

    In the innovaTV 204 clinical trial, TIVDAK was evaluated in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Results from the trial showed a 24 percent confirmed objective response rate (ORR) (95% CI; 15.9-33.3), as assessed by an independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The median duration of response (DOR) was 8.3 months (95% CI; 4.2 to not reached).

    The prescribing information for TIVDAK includes a BOXED WARNING for ocular toxicity, and Warnings for peripheral neuropathy, hemorrhage, pneumonitis, and embryo-fetal toxicity. The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), peripheral neuropathy (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%). Please see Important Safety Information below.1

    "We are thrilled to see this new treatment approved by the FDA. We are grateful to have another option for this devastating disease," said Tamika Felder, Founder, Cervivor.

    "We are pleased with the accelerated approval of TIVDAK, Seagen's third FDA-approved antibody-drug conjugate, and fourth approved medicine. Our mission at Seagen is to develop medicines that make a difference for people impacted by cancer," said Roger Dansey, M.D., Chief Medical Officer, Seagen.

    "TIVDAK's approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "The journey towards the approval of TIVDAK started nearly two decades ago with innovative research by scientists at Genmab and Seagen and reflects on our purpose of making an impact in the lives of cancer patients and their families. Today's announcement marks Genmab's evolution into a fully integrated biotechnology company and we would like to thank patients, caregivers, investigators and our collaborators for their participation in our clinical studies."

    The Biologics License Application (BLA) for TIVDAK was submitted in February 2021 and accepted with Priority Review in April 2021. The submission was based on the results of the innovaTV 204 trial.

    The FDA's Accelerated Approval Program allows for approval of a medicine based on a surrogate endpoint that is reasonably likely to predict clinical benefit, if the medicine fills an unmet medical need for a serious condition. A global, randomized phase 3 clinical trial (innovaTV 301) is underway and is also intended to support global registrations.

    About Cervical Cancer

    It is estimated that in 2021, more than 14,480 new cases of invasive cervical cancer will be diagnosed in the U.S., and 4,290 women will die from the disease.2 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying of the disease in 2018.3

    About the innovaTV 204 Trial

    The innovaTV 204 trial (NCT03438396/GOG-3023/ENGOT-cx6) is an open-label, multicenter, single-arm phase 2 trial that evaluated tisotumab vedotin in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Patients were excluded if they had active ocular surface disease, any prior episode of cicatricial conjunctivitis or Stevens-Johnson syndrome, Grade ≥2 peripheral neuropathy or known coagulation defects leading to an increased risk of bleeding. The main efficacy outcome measures were confirmed ORR per RECIST v1.1 as assessed by an IRC and DOR.1

    The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the GOG Foundation, Inc. (GOG). For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

    About TIVDAK (tisotumab vedotin-tftv)

    TIVDAK (tisotumab vedotin-tftv) is an ADC composed of Genmab's human monoclonal antibody directed to tissue factor (TF) and Seagen's ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of TIVDAK is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, TIVDAK also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.1

    TIVDAK (tisotumab vedotin-tftv) for injection, for intravenous use, 40 mg Important Safety Information

    BOXED WARNING: OCULAR TOXICITY

    TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

    Warnings and Precautions

    Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8% of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose.

    In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse, including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

    Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

    Peripheral neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barré syndrome.

    Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

    Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients.

    Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

    Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

    Monitor patients for pulmonary symptoms indicative of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

    Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

    Embryo-fetal toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

    Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

    The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

    Drug interactions

    Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

    Use in Specific Populations

    Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

    Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

    Please see full prescribing information, including BOXED WARNING for TIVDAK here.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About Genmab

    Genmab is an international biotechnology company with a core purpose to improve the lives of people with cancer. For more than 20 years, Genmab's vision to transform cancer treatment has driven its passionate, innovative and collaborative teams to invent next-generation antibody technology platforms and leverage translational research and data sciences, fueling multiple differentiated cancer treatments that make an impact on people's lives. To develop and deliver novel therapies to patients, Genmab has formed 20+ strategic partnerships with biotechnology and pharmaceutical companies. Genmab's proprietary pipeline includes bispecific T-cell engagers, next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates.

    Genmab is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.

    About the Seagen and Genmab Collaboration

    Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.

    Seagen Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the continued FDA approval of TIVDAK (tisotumab vedotin-tftv) for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy; the conduct of an ongoing randomized phase 3 clinical trial (innovaTV 301) intended to verify the clinical benefit of TIVDAK and support global registrations; and the therapeutic potential of TIVDAK, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that innovaTV 301 and subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; that utilization and adoption of TIVDAK by prescribing physicians may be limited by the availability and extent of reimbursement and other factors; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    Genmab Forward Looking Statements

    This Company Announcement contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab's most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab's most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

    Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo. TIVDAKTM and the TIVDAK logo are trademarks owned by Seagen Inc.

    References:

    1 TIVDAK [package insert]. Bothell, WA: Seagen, Inc.

    2 Cancer Stat Facts: Cervical Cancer. National Cancer Institute website. https://seer.cancer.gov/statfacts/html/cervix.html. Accessed September 16, 2021.

    3 Bray F, Ferlay J, Soerjomataram I, et al. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2018;0: 1-31.

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  3. - Tisotumab Vedotin in Combination with Carboplatin Showed Encouraging, Durable Anti-Tumor Activity as First-Line Treatment -

    - Tisotumab Vedotin in Combination with Pembrolizumab Showed Encouraging, Durable Anti-Tumor Activity in Previously Treated Patients -

    Seagen Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today presented interim data from two cohorts of the phase 1b/2 innovaTV 205 multi-cohort, open-label trial of tisotumab vedotin in recurrent or metastatic cervical cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2021 as part of a featured mini oral presentation. Initial results from these two dose expansion cohorts of the study showed encouraging and durable anti-tumor activity with tisotumab vedotin…

    - Tisotumab Vedotin in Combination with Carboplatin Showed Encouraging, Durable Anti-Tumor Activity as First-Line Treatment -

    - Tisotumab Vedotin in Combination with Pembrolizumab Showed Encouraging, Durable Anti-Tumor Activity in Previously Treated Patients -

    Seagen Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today presented interim data from two cohorts of the phase 1b/2 innovaTV 205 multi-cohort, open-label trial of tisotumab vedotin in recurrent or metastatic cervical cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2021 as part of a featured mini oral presentation. Initial results from these two dose expansion cohorts of the study showed encouraging and durable anti-tumor activity with tisotumab vedotin in combination with carboplatin (Cohort D) as first-line therapy for patients with advanced cervical cancer who had not received prior systemic therapy, with a 55% objective response rate (ORR) and with tisotumab vedotin in combination with pembrolizumab (Cohort F) for patients with advanced cervical cancer who experienced disease progression after 1-2 lines of prior systemic therapy, with a 38% ORR. Both combinations demonstrated a manageable and acceptable safety profile, with no new safety signals identified.

    "For patients diagnosed with recurrent or metastatic cervical cancer, there is a need for additional treatment options in the first-, second- and third-line settings," said Ignace B. Vergote, M.D., Ph.D., co-founder of European Network of Gynaecological Oncological Trial groups (ENGOT), and lead investigator on the innovaTV 205/ENGOT-cx8/GOG-3024 clinical trial. "Interim results from the innovaTV 205 study show the potential for tisotumab vedotin to treat these patients with encouraging response rates in combination with carboplatin and also in combination with pembrolizumab."

    "As we advance our clinical development program for tisotumab vedotin into earlier lines of therapy in cervical cancer, we're encouraged by these interim results of the combination cohorts with tisotumab vedotin," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "Based on these results from the innovaTV 205 study, we also plan to evaluate tisotumab vedotin further in various combinations in first-line metastatic or recurrent cervical cancer."

    "We are pleased to share the initial results from the innovaTV 205 study, as these data build upon our understanding of the potential for tisotumab vedotin as a combination therapy in first- and second-line treatment of recurrent or metastatic cervical cancer," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "We recognize the need for new therapies for patients with cervical cancer globally and are committed to advancing the tisotumab vedotin development program."

    Tisotumab Vedotin (TV) + Carboplatin (Carbo) in First-line (1L) or + Pembrolizumab (Pembro) in Previously Treated (2L/3L) Recurrent or Metastatic Cervical Cancer (r/mCC): Interim Results of ENGOT-cx8/GOG-3024/innovaTV 205 Study (Presentation #723MO, mini oral presentation on Sunday, September 19)

    1L TV + Carbo Dose Expansion Cohort Interim Results

    Within this cohort, recurrent or metastatic cervical cancer patients who had not received any prior systemic therapy were given the recommended phase 2 dose of tisotumab vedotin 2.0 mg/kg plus carboplatin AUC 5 Q3W.

    Efficacy:

    • The primary endpoint of ORR was 55% (n=18/33 patients), with four patients achieving complete responses and 14 patients achieving partial responses.
    • Median time to response was 1.4 months (range 1.1-4.4), with median follow up of 7.9 months and median duration of response of 8.3 months (95% CI: 4.2-NR).
    • Median progression-free survival (PFS) was 9.5 months (95% CI: 4.0-NR).

    Safety:

    • Grade ≥3 adverse events (AE) occurred in 78.8% of patients (n=26/33), with 57.6% (n=19/33) of patients experiencing Grade ≥3 AEs related to treatment with tisotumab vedotin.
    • Adverse events of special interest (AESI) included ocular events (Grade 1-2: 57.6%; Grade ≥3: 9.1%), bleeding (Grade 1-2: 51.5%; Grade ≥3: 6.1%) and peripheral neuropathy (Grade 1-2: 48.5; Grade ≥3: 12.1%).

    2L/3L TV + Pembro Dose Expansion Cohort Results Interim Results

    Within this cohort, recurrent or metastatic cervical cancer patients who had received 1-2 prior systemic therapies were given the recommended phase 2 dose of tisotumab vedotin 2.0 mg/kg plus pembrolizumab 200 mg Q3W.

    Efficacy:

    • The primary endpoint of ORR was 38% (n=13/34 patients), with two patients achieving complete responses and 11 patients achieving partial responses.
    • Median time to response was 1.4 months (range 1.3-5.8), with median follow-up of 13.0 months and a median duration of response of 13.8 months (95% CI: 2.8-NR).
    • Median PFS was 5.6 months (95% CI: 2.7-13.7).

    Safety:

    • Grade ≥3 AEs occurred in 74.3% of patients (n=26/35), with 45.7% (n=16/35) of patients experiencing Grade ≥3 AEs related to treatment with tisotumab vedotin.
    • AESI included ocular events (Grade 1-2: 51.4%; Grade ≥3: 2.9%), bleeding (Grade 1-2: 57.1%; Grade ≥3: 8.6%) and peripheral neuropathy (Grade 1-2: 37.1%; Grade ≥3: 2.9%), with one patient experiencing a Grade 4 bleeding event.

    Additionally, Seagen and Genmab presented data from dose-escalation cohorts of the innovaTV 205 study at the 2021 International Gynecologic Cancer Society (IGCS) Annual Meeting held August 30-September 2, 2021.

    About Cervical Cancer

    Cervical cancer originates in the cells lining the cervix. In 2021, an estimated 14,480 new cases of invasive cervical cancer will be diagnosed in the U.S., and 4,290 women will die from the disease.1 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women are in the developing world.2 Routine medical examinations and human papillomavirus (HPV) vaccines have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic. Current therapies for previously treated recurrent or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent, with median overall survival ranging from 6.0 to 9.4 months.3,4,5,6,7,8,9,10

    About the innovaTV 205 Trial

    The innovaTV 205 trial (also known as ENGOT-cx8/GOG-3024) is a phase 1b/2 open-label, multi-center trial of tisotumab vedotin monotherapy and in combination with bevacizumab, pembrolizumab or carboplatin in patients with recurrent or metastatic cervical cancer. The study consists of two parts: dose escalation (Cohorts A, B, and C) and dose expansion (Cohorts D, E, F and G). Patients enrolled in the dose escalation cohorts have progressed during or after standard of care therapy or are intolerant or ineligible to receive standard of care treatments. The primary objective is to identify and establish the maximum tolerated dose and Recommended Phase 2 Dose (RP2D) of tisotumab vedotin as combination therapy. Within the dose expansion cohorts, patients with recurrent or metastatic cervical cancer who have not previously received prior systemic therapy are treated in Cohorts D and E, with patients who have progressed on or after standard of care treatments evaluated in Cohorts F and G.

    For more information about the innovaTV 205 clinical trial and the study collaborators, visit here, and to learn more about other clinical trials with tisotumab vedotin, visit clinicaltrials.gov.

    About Tisotumab Vedotin

    Tisotumab vedotin is an antibody-drug conjugate (ADC) composed of Genmab's fully human monoclonal antibody specific for tissue factor and Seagen's ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing programmed cell death. In cancer biology, tissue factor is a cell-surface protein and is associated with tumor growth, angiogenesis, metastasis and poor prognosis.11 Tissue factor was selected as a target for an ADC approach based on its increased levels of expression on multiple solid tumors and its rapid internalization.

    Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial called innovaTV 301 versus investigator's choice of chemotherapy in recurrent or metastatic cervical cancer. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability. Enrollment is ongoing and the study is intended to support global registrations. More information about the innovaTV 301 clinical trial, including enrolling sites, is available here. In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer.

    Additional clinical studies for tisotumab vedotin include phase 2 studies in second-/third-line recurrent or metastatic cervical cancer as monotherapy (innovaTV 204), phase 2 study in first-/second-line recurrent or metastatic cervical cancer as monotherapy or in combination with other agents (innovaTV 205) and additional studies in various solid tumors.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About Genmab

    Genmab is an international biotechnology company with a core purpose to improve the lives of patients with cancer. Founded in 1999, Genmab is the creator of multiple approved antibody therapeutics that are marketed by its partners. The company aims to create, develop and commercialize differentiated therapies by leveraging next-generation antibody technologies, expertise in antibody biology, translational research and data sciences and strategic partnerships. To create novel therapies, Genmab utilizes its next-generation antibody technologies, which are the result of its collaborative company culture and a deep passion for innovation. Genmab's proprietary pipeline consists of modified antibody candidates, including bispecific T-cell engagers and next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates. The company is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com.

    About the Seagen and Genmab Collaboration

    Tisotumab vedotin is being co-developed by Seagen and Genmab, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.

    Seagen Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of tisotumab vedotin including its efficacy, safety and therapeutic uses, the clinical development program for tisotumab vedotin and the potential for the innovaTV 301 trial to support global registrations. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the inability to show sufficient activity in current and future clinical trials and the possibility of adverse regulatory actions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    Genmab Forward Looking Statements

    This Media Release contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab's most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab's most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Media Release nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

    Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo®; HuMax®; DuoBody®; DuoBody in combination with the DuoBody logo®; HexaBody®; HexaBody in combination with the HexaBody logo®; DuoHexaBody® and HexElect®.


    1 Cancer Stat Facts: Cervical Cancer. National Cancer Institute website. https://seer.cancer.gov/statfacts/html/cervix.html. Accessed September 13, 2021.

    2 Bray et al., CA Cancer J Clin 2018; 0:1-31.

    3 Miller et al., Gynecol Oncol 2008; 110:65.

    4 Santin et al., Gynecol Oncol 2011; 122:495.

    5 Bookman et al., Gynecol Oncol 2000; 77:446.

    6 Garcia et al., Am J Clin Oncol 2007; 30:428.

    7 Monk et al., J Clin Oncol 2009; 27:1069.

    8 Santin et al., Gynecol Oncol 2011; 122:495.

    9 Schilder et al., Gynecol Oncol 2005; 96:103.

    10 Chung HC et al. J Clin Oncol 2019; 37:1470.

    11 Rondon et al. Semin Thromb Hemost 2019; 45:396–412.

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  4. Seagen Inc. (NASDAQ:SGEN) today announced that management will participate in a virtual fireside chat at the Morgan Stanley 19th Annual Global Healthcare Conference on Monday, September 13, 2021 at 2:00 p.m. Eastern Time. The presentation will be webcast live and available for replay from Seagen's website at www.seagen.com in the Investors section.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit…

    Seagen Inc. (NASDAQ:SGEN) today announced that management will participate in a virtual fireside chat at the Morgan Stanley 19th Annual Global Healthcare Conference on Monday, September 13, 2021 at 2:00 p.m. Eastern Time. The presentation will be webcast live and available for replay from Seagen's website at www.seagen.com in the Investors section.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

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  5. - Data from Phase 1/2 innovaTV 205 Trial Evaluating Tisotumab Vedotin Combination Therapy in Recurrent or Metastatic Cervical Cancer to be Featured in Mini Oral Presentation -

    Seagen Inc. (NASDAQ:SGEN) today announced data and trials in progress from its diverse and growing portfolio of marketed and investigational therapies will be presented at the virtual European Society for Medical Oncology (ESMO) 2021 Annual Meeting, to be held from September 16-21. Sixteen presentations will demonstrate the breadth of Seagen's portfolio and development activities, across multiple cancer types - including a mini oral presentation featuring results from the Phase 1/2 innovaTV 205 clinical trial in recurrent or metastatic cervical cancer.

    The innovaTV…

    - Data from Phase 1/2 innovaTV 205 Trial Evaluating Tisotumab Vedotin Combination Therapy in Recurrent or Metastatic Cervical Cancer to be Featured in Mini Oral Presentation -

    Seagen Inc. (NASDAQ:SGEN) today announced data and trials in progress from its diverse and growing portfolio of marketed and investigational therapies will be presented at the virtual European Society for Medical Oncology (ESMO) 2021 Annual Meeting, to be held from September 16-21. Sixteen presentations will demonstrate the breadth of Seagen's portfolio and development activities, across multiple cancer types - including a mini oral presentation featuring results from the Phase 1/2 innovaTV 205 clinical trial in recurrent or metastatic cervical cancer.

    The innovaTV 205 trial of tisotumab vedotin (TV) is designed to evaluate the safety and efficacy of TV as monotherapy and in combination with chemotherapy and other agents in recurrent or metastatic cervical cancer. Data to be shared will include interim analyses of TV plus carboplatin as a potential first-line therapy, as well as analyses of TV plus pembrolizumab in previously treated patients.

    Seagen's Biologics License Application for TV monotherapy in recurrent or metastatic cervical cancer is currently under Priority Review by the U.S. Food and Drug Administration (FDA) with a target action date of Oct. 10, 2021.

    "The data to be shared at ESMO 2021 reflect our commitment to developing transformational cancer medicines for patients in areas of significant unmet medical need, including best-in-class antibody-drug conjugates," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Our research to advance antibody-drug conjugates as monotherapies or in combination with other therapies for the treatment of various cancers has the potential to shape future treatment paradigms."

    Other research presentations include subset analyses of EV-301, a phase 3 trial of enfortumab vedotin (EV) versus chemotherapy for previously treated advanced urothelial carcinoma, and the first data from a weekly-dosing trial of ladiratuzumab vedotin (LV), an investigational anti-LIV-1 antibody-drug conjugate, in pre-treated metastatic triple-negative breast cancer.

    Data to be presented at ESMO 2021 for Seagen medicines and investigational agents:

    Presentation #

    Abstract Title

    Lead

    Author

    Presentation

    Type

    Tisotumab Vedotin

    723MO

    Tisotumab Vedotin (TV) + Carboplatin (Carbo) in First-line (1L) or + Pembrolizumab (Pembro) in Previously Treated (2L/3L) Recurrent or Metastatic Cervical Cancer (r/mCC): Interim Results of ENGOT-Cx8/GOG-3024/innovaTV 205 Study

    I. Vergote

    Mini Oral Session – Gynaelogical Cancers, Sunday, September 19, 5:30-5:35 PM CEST

    930TiP

    innovaTV 207: New Dosing Cohort in the Open Label Phase 2 Study of Tisotumab Vedotin in Solid Tumors

    D. Hong

    On Demand E-Poster

    PADCEV® (enfortumab vedotin)

    698P

    Analysis of hard-to-treat subgroups from EV-301, a phase 3 trial of enfortumab vedotin (EV) vs chemotherapy for previously treated advanced urothelial carcinoma

    J. Rosenberg

    On Demand E-Poster

    705P

    Systematic literature review (SLR) and network meta-analysis (NMA) of first-line (1L) therapies for locally advanced/metastatic urothelial carcinoma (la/mUC)

    L. Bloudek

    On Demand E-Poster

    704P

    Treatment Patterns Among Patients with Advanced Urothelial Carcinoma (aUC) in the US

    A. Morgans

    On Demand E-Poster

    TUKYSA® (tucatinib)

    331TiP

    HER2CLIMB-04: Phase 2 Trial of Tucatinib + Trastuzumab Deruxtecan in Patients With HER2+ Locally Advanced or Metastatic Breast Cancer With and Without Brain Metastases (Trial in Progress)

    L. Carey

    On Demand E-Poster

    1434TiP

    MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma (GEC): Trial in Progress

    D. Catenacci

    On Demand E-Poster

    557TiP

    SGNTUC-019: Phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations (Trial in Progress)

    M. Reck

    On Demand E-Poster

    1437TiP

    Phase 1b/2, open label, dose escalation and expansion trial of tucatinib in combination with trastuzumab and oxaliplatin-based chemotherapy in patients with unresectable or metastatic HER2+ gastrointestinal cancers (Trial in Progress)

    H. Park

    On Demand E-Poster

    439P

    Characteristics and treatment patterns among patients with HER2-amplified advanced/metastatic colorectal cancer (mCRC): a clinical-genomic database study

    J. Strickler

    On Demand E-Poster

    Ladiratuzumab Vedotin

    259P

    Weekly ladiratuzumab vedotin monotherapy for metastatic triple negative breast cancer

    M. Tsai

    On Demand E-Poster

    643TiP

    Open-Label, Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors (SGNLVA-005, Trial in Progress)

    HT. Arkenau

    On Demand E-Poster

    ADCETRIS® (brentuximab vedotin)

    1029TiP

    Phase 2 Trial of Pembrolizumab (Pembro) and Brentuximab Vedotin (BV) in Patients With Metastatic Solid Malignancies After Progression on Prior Programmed Cell Death Protein (PD)-1 Inhibitors (SGN35-033, Trial in Progress)

    C. Lance Cowey

    On Demand E-Poster

    Early Pipeline

    555TiP

    A First-in-Human Trial of the Integrin Beta-6-Targeted Antibody–Drug Conjugate, SGN-B6A, in Patients With Advanced Solid Tumors (SGNB6A-001, Trial in Progress)

    E. Calvo

    On Demand E-Poster

    556TiP

    A Phase 1 Study of SGN-STNV, a Novel Antibody–Drug Conjugate Targeting Sialyl-Thomsen-nouveau Antigen (STn), in Adults With Advanced Solid Tumors (SGNSTNV-001)

    N. Lakhani

    On Demand E-Poster

    558TiP

    Phase 1 Study of Effector-function Enhanced Monoclonal Antibody (mAb), SEA-TGT, in Advanced Malignancies (SGNTGT-001, Trial in Progress)

    V. Ribrag

    On Demand E-Poster

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of Seagen's products and product candidates, the company's pipeline and the advancement of its research and development activities. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the risk of adverse events or safety signals, the inability to show sufficient activity in clinical trials, the possibility of adverse regulatory actions, and the potential for delays or setbacks in product development and the regulatory review process. More information about the risks and uncertainties faced by the company is contained under the caption "Risk Factors" included in Seagen's Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise except as required by applicable law.

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  6. – Seagen Licenses Disitamab Vedotin, a Novel HER2-targeted Antibody-Drug Conjugate (ADC) from RemeGen –

    – Disitamab Vedotin has Shown Potential as a Differentiated ADC Across a Range of HER2 Expressing Tumors and is Being Developed as Monotherapy and in Combination with PD-1 Inhibitors, Further Expanding and Complementing Seagen's Deep and Diverse Pipeline –

    – Agreement Leverages Seagen and RemeGen's Leadership and Expertise in Developing ADCs as well as Seagen's Global Development and Commercialization Capabilities –

    Seagen Inc. (NASDAQ:SGEN), a world leader and pioneer in antibody-drug conjugate (ADC) therapies, and RemeGen Co., Ltd. (9995.HK), a leading innovative biopharmaceutical company in China, today announced that the two companies…

    – Seagen Licenses Disitamab Vedotin, a Novel HER2-targeted Antibody-Drug Conjugate (ADC) from RemeGen –

    – Disitamab Vedotin has Shown Potential as a Differentiated ADC Across a Range of HER2 Expressing Tumors and is Being Developed as Monotherapy and in Combination with PD-1 Inhibitors, Further Expanding and Complementing Seagen's Deep and Diverse Pipeline –

    – Agreement Leverages Seagen and RemeGen's Leadership and Expertise in Developing ADCs as well as Seagen's Global Development and Commercialization Capabilities –

    Seagen Inc. (NASDAQ:SGEN), a world leader and pioneer in antibody-drug conjugate (ADC) therapies, and RemeGen Co., Ltd. (9995.HK), a leading innovative biopharmaceutical company in China, today announced that the two companies have entered into an exclusive worldwide licensing agreement to develop and commercialize disitamab vedotin, a novel HER2-targeted ADC.

    Disitamab vedotin combines the drug-linker technology originally developed by Seagen with RemeGen's novel HER2 antibody exhibiting higher affinity and an increased internalization rate as compared to trastuzumab in preclinical models.1, 2 As monotherapy, disitamab vedotin has demonstrated antitumor activity in clinical trials in several solid tumor types, including urothelial, gastric and breast cancer, as well as across a spectrum of HER2 expression levels. In addition, promising combination activity was demonstrated with a PD-1 inhibitor in urothelial cancer.3 It is believed that vedotin-based immunogenic cell death (ICD) may differentiate this class of ADC's when combined with checkpoint inhibitors.

    "This collaboration leverages Seagen's world-class expertise and knowledge of ADC development, manufacturing and commercialization to maximize the potential of disitamab vedotin. It also complements our existing franchises and our deep and diverse portfolio of innovative anti-cancer therapies for patients in need," said Clay Siegall, Ph.D., President and CEO, Seagen. "The addition of disitamab vedotin as a late-stage asset with multiple development opportunities aligns strategically with our plans to continue expanding our global footprint and deliver meaningful therapies to patients around the world."

    Disitamab vedotin received U.S. Food and Drug Administration (FDA) Breakthrough Therapy designation in 2020 for use in second-line treatment of patients with HER2-expressing, locally advanced or metastatic urothelial cancer (mUC) who have previously received platinum-containing chemotherapy. In the same year, RemeGen announced FDA's clearance of an Investigational New Drug (IND) application for a Phase II clinical trial in mUC. Disitamab vedotin is conditionally approved for treating locally advanced metastatic gastric cancer in China, and in July 2021 the National Medical Products Administration (NMPA) of China also accepted a New Drug Application for disitamab vedotin in mUC.

    "Disitamab vedotin has demonstrated robust antitumor activity in multiple advanced cancers where no effective therapy is available," said Jianmin Fang, Ph.D., Co-founder, CEO and CSO, RemeGen. "Seagen is a well-known global biotechnology company recognized for its capabilities in the field of oncology and ADC therapies. We are delighted to partner with Seagen to maximize the potential of disitamab vedotin and to make it available to patients worldwide. We believe this license agreement highlights the global potential of disitamab vedotin in the ADC arena and is a major milestone for us as we begin the journey to transform from a domestic to a global biopharmaceutical company."

    Under the terms of the agreement, Seagen will make a $200 million upfront payment to exclusively license rights to disitamab vedotin for global development and commercialization, outside of RemeGen's territory. RemeGen will retain development and commercialization rights for Asia, excluding Japan and Singapore. Seagen will lead global development and RemeGen will fund and operationalize the portion of global clinical trials attributable to its territory. RemeGen will also be responsible for all clinical development and regulatory submissions specific to its territory.

    Seagen will pay RemeGen up to $2.4 billion in potential total milestone payments based upon the achievement of specified development, regulatory and commercialization goals across multiple indications and products. RemeGen will be entitled to a tiered, high single digit to mid-teen percentage royalty based on net sales of disitamab vedotin in Seagen's territory.

    About Disitamab Vedotin (RC48)

    Disitamab vedotin is a novel ADC that selectively delivers the anti-cancer agent monomethyl auristatin E (MMAE) into HER2-expressing tumor cells. The novel antibody component of the ADC exhibits a higher affinity and increased internalization rate as compared to trastuzumab in preclinical models, and in animal models, demonstrates promising antitumor activity. It is the first domestically developed ADC in China to receive marketing approval. In June 2021, disitamab vedotin received conditional approval by the NMPA of China to treat locally advanced or metastatic gastric cancer (GEJ carcinoma). In July 2021, the NMPA accepted the New Drug Application for disitamab vedotin in locally advanced or metastatic urothelial carcinoma. In addition, disitamab vedotin has shown significant antitumor activity in clinical trials of a number of HER2-expressing cancers, including those with low HER2 expression. It is currently being studied in multiple late-stage clinical trials across several solid tumor types.

    About RemeGen

    RemeGen Co., Ltd. (RemeGen) is a leading fully integrated biopharmaceutical company in China committed to the discovery, development and commercialization of innovative and differentiated biologics for the treatment of autoimmune, oncology and ophthalmic diseases with unmet medical needs in China and globally. RemeGen's main focus is research and development, manufacturing and commercialization of novel biologics, most notably monoclonal antibodies (mAb) and antibody-drug conjugates (ADCs). Headquartered in Yantai, Shandong Province, China, RemeGen has labs/offices in Beijing, Shanghai, California and Maryland. Since its inception in 2008, RemeGen has created more than 10 novel drug molecules that are in various stages of development. Currently, there are two products that have been approved and marketed in China to treat autoimmune and oncology indications. For more information about RemeGen, please visit: www.remegen.com.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Seagen Forward-Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of disitamab vedotin and the potential development and commercialization of disitamab vedotin in regions outside Greater China; and other statements that are not historical facts. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, but are not limited to, risks associated with licensing transactions, such as the risks that disitamab vedotin will not be integrated into Seagen's pipeline successfully or will not perform as anticipated, in which case, Seagen may not recover its investment in disitamab vedotin; and risks related to the development and commercialization of disitamab vedotin, including the risk that Seagen or RemeGen may be delayed or unsuccessful in planned clinical trial initiations, enrollment in and conduct of clinical trials, obtaining data from clinical trials, regulatory submissions, and regulatory approvals in the U.S. and in other countries in each case for a variety of reasons including the difficulty and uncertainty of pharmaceutical product development, negative or disappointing clinical trial results, unexpected adverse events or regulatory actions and the inherent uncertainty associated with the regulatory approval process; and risks related to the duration and severity of the COVID-19 pandemic and resulting global economic, financial and healthcare system disruptions More information about the risks and uncertainties faced by Seagen is contained in the Company's quarterly report on Form 10-Q for the quarter ended June 30, 2021, filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    REFERENCES:

    1.
    Yao et al., Breast Cancer Res Treat (2015) 153:123-133, company data.

    2. Data on file at Seagen.

    3. PD1 combo solid tumor basket study is ongoing in HER2 1+expressing patients in China (breast, gastric, urothelial). A separate urothelial trial is also ongoing in China, HER2 allcomers.

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  7. -Record Quarterly Sales for Each of ADCETRIS, PADCEV and TUKYSA; Total Net Product Sales of $347.3 Million in 2Q21, an Increase of 44 Percent Over 2Q20-

    -FDA Grants PADCEV Regular Approval and Adds New Indication for Locally Advanced or Metastatic Urothelial Cancer-

    -Tisotumab Vedotin BLA Under FDA Priority Review with PDUFA Date of October 10, 2021-

    -Conference Call Today at 4:30 p.m. ET-

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the second quarter and six months ended June 30, 2021. The Company also highlighted ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib) commercial and development accomplishments, as well as progress across its robust oncology pipeline.

    "The commercial…

    -Record Quarterly Sales for Each of ADCETRIS, PADCEV and TUKYSA; Total Net Product Sales of $347.3 Million in 2Q21, an Increase of 44 Percent Over 2Q20-

    -FDA Grants PADCEV Regular Approval and Adds New Indication for Locally Advanced or Metastatic Urothelial Cancer-

    -Tisotumab Vedotin BLA Under FDA Priority Review with PDUFA Date of October 10, 2021-

    -Conference Call Today at 4:30 p.m. ET-

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the second quarter and six months ended June 30, 2021. The Company also highlighted ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib) commercial and development accomplishments, as well as progress across its robust oncology pipeline.

    "The commercial execution across our three brands continues to be strong, achieving record quarterly net product sales for each of ADCETRIS, PADCEV and TUKYSA, as we bring these important medicines to patients around the world," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seagen. "We are investing in clinical trials to maximize the potential of our three approved drugs, and making strong progress with TUKYSA commercialization in the European Union. Looking ahead to the remainder of 2021, Seagen is poised to add a fourth product, tisotumab vedotin, which has an FDA action date in October 2021 and we expect continued progress across our earlier-stage oncology pipeline with planned clinical data presentations and other development accomplishments."

    PROGRAM HIGHLIGHTS

    PADCEV

    • Received FDA Regular Approval and Additional Indication for mUC: In July 2021, Seagen and Astellas announced that the U.S. Food and Drug Administration (FDA) granted PADCEV regular approval, in addition to approving a new indication for adult patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. Cisplatin-ineligible patients typically have limited treatment options and a poor prognosis.
    • Presented Updated Results from Cohort 2 of Pivotal EV-201 Trial: In June 2021, updated results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting for the second cohort of the EV-201 trial for patients with la/mUC who received prior treatment with an immunotherapy but had not received a platinum-containing chemotherapy and were ineligible for cisplatin chemotherapy. The data showed that with extended follow-up median duration of response increased to 13.8 months. EV-201 results were also published in The Lancet Oncology and supported expansion of the PADCEV label in July 2021.
    • Presented Updated Results from the EV-103 Trial in First-line mUC: In June 2021, updated durability and long-term outcome data were presented at ASCO for the initial cohort of the EV-103 trial combining PADCEV and KEYTRUDA® (pembrolizumab) for first-line treatment of la/mUC. The updated data after a median follow-up of two years showed median duration of response of 25.6 months and a median overall survival of 26.1 months. The long-term analysis demonstrated a safety profile generally consistent with previous findings. The Company is evaluating the combination in a randomized Cohort K of the EV-103 trial, which is expected to complete enrollment by the end of 2021 and potentially support registration under the FDA's accelerated approval pathway.

    TUKYSA

    • Presented Long-Term Results for HER2CLIMB Trial at ASCO: In June 2021, updated analyses of the pivotal HER2CLIMB trial evaluating the addition of TUKYSA to trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer with and without brain metastases were presented at ASCO. The data confirmed the overall survival benefit of TUKYSA originally observed with median overall survival for the TUKYSA arm extending to two years. The survival benefit was maintained across all prespecified patient subgroups. The safety profile was generally consistent with the primary analysis.

    ADCETRIS

    • Published 5-year Follow-up Results for ECHELON-1: In June 2021, five-year follow-up results from the ECHELON-1 phase 3 clinical trial were published in Lancet Haematology. Data showed treatment with ADCETRIS in combination with AVD (Adriamycin [doxorubicin], vinblastine and dacarbazine) resulted in superior long-term outcomes when compared to ABVD, which includes bleomycin, in frontline advanced Hodgkin lymphoma.

    Tisotumab Vedotin

    • Tisotumab Vedotin BLA Accepted for Priority Review: In April 2021, FDA accepted for Priority Review the tisotumab vedotin BLA for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The target FDA action date is October 10, 2021. The submission is based on the results of the innovaTV 204 pivotal phase 2 trial, which were published in The Lancet Oncology in April 2021.

    For additional information on Seagen's pipeline, visit www.seagen.com/science/pipeline.

    SECOND QUARTER AND SIX-MONTHS 2021 FINANCIAL RESULTS

    Revenues: Total revenues for the second quarter and six months ended June 30, 2021 increased to $388.5 million and $720.5 million, respectively, compared to $278.0 million and $512.5 million for the same periods in 2020. Growth over 2020 was primarily driven by higher sales of PADCEV and the addition of TUKYSA to the Company's commercial portfolio. Revenues are composed of the following three components:

    • Net Product Sales:

    Three months ended June 30,

     

    Six months ended June 30,

    (dollars in millions)

    2021

     

    2020

    % Change

     

    2021

     

    2020

    % Change

    Total Net Product Sales

    $

    347.3

     

     

    $

    240.5

     

    44%

     

    $

    649.9

     

     

    $

    439.0

     

    48%

    ADCETRIS

    181.9

     

     

    167.5

     

    9%

     

    344.5

     

     

    331.6

     

    4%

    PADCEV

    82.4

     

     

    57.2

     

    44%

     

    152.2

     

     

    91.6

     

    66%

    TUKYSA

    83.0

     

     

    15.8

     

    427%

     

    153.3

     

     

    15.8

     

    873%

    Note: Sum of product sales may not equal total net product sales due to rounding.

    • Royalty Revenues: Royalty revenues for the second quarter and year-to-date in 2021 were $36.3 million and $63.5 million, respectively, compared to $31.2 million and $51.6 million for the same periods in 2020. Royalty revenues are primarily driven by sales of ADCETRIS outside the U.S. and Canada by Takeda and, to a lesser extent, royalties from sales of Polivy® (polatuzumab vedotin) by Roche and Blenrep® (belantamab mafodotin) by GlaxoSmithKline, which are ADCs that use Seagen technology.
    • Collaboration and License Agreement Revenues: Amounts earned under the Company's product, development and technology collaborations were $4.8 million and $7.0 million in the second quarter and year-to-date in 2021, respectively, compared to $6.3 million and $21.9 million for the same periods in 2020. Collaboration revenues for the year-to-date in 2020 included a regulatory milestone related to Polivy under the collaboration with Roche.

    Cost of Sales: Cost of sales for the second quarter and year-to-date in 2021 were $78.1 million and $142.2 million, respectively, compared to $48.2 million and $77.7 million for the same periods in 2020. The increase was primarily due to the PADCEV gross profit share with Astellas, which was $38.6 million and $71.1 million in the second quarter and year-to-date of 2021, respectively, compared to $27.1 million and $43.5 million for the same periods in 2020. The increase in cost of sales also reflected amortization of acquired in-process technology costs that began with the approval of TUKYSA in April 2020, and third-party royalties owed for ADCETRIS, PADCEV and TUKYSA net product sales, in addition to cost of products sold.

    Research and Development (R&D) Expenses: R&D expenses for the second quarter and year-to-date in 2021 were $234.9 million and $465.3 million, respectively, compared to $198.1 million and $393.3 million for the same periods in 2020. The increase in 2021 primarily reflected continued investment in clinical development of the Company's approved drugs and to advance novel programs and technologies.

    Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the second quarter and year-to-date in 2021 were $165.1 million and $325.0 million, respectively, compared to $125.6 million and $247.9 million for the same periods in 2020. The increases in 2021 primarily reflected investments to support European TUKYSA launches and our global expansion efforts.

    Non-cash, share-based compensation expense for the first six months of 2021 was $76.0 million, compared to $68.4 million for the same period in 2020.

    Net Loss: Net loss for the second quarter of 2021 was $84.6 million, or $0.47 per diluted share, compared to net loss of $21.2 million, or $0.12 per diluted share, for the second quarter of 2020. Net loss for the six months ended June 30, 2021 was $206.0 million, or $1.14 per diluted share, compared to net loss of $189.6 million, or $1.10 per diluted share, for the same period in 2020.

    Cash and Investments: As of June 30, 2021, Seagen had $2.5 billion in cash and investments.

    2021 FINANCIAL OUTLOOK

    Seagen anticipates 2021 revenues, operating expenses and other costs to be in the ranges shown in the table below, unchanged from the Company's previous financial guidance provided on February 11, 2021.

    Revenues

    ADCETRIS net product sales

    $675 million to $700 million

    PADCEV net product sales

    $310 million to $325 million

    TUKYSA net product sales

    $300 million to $315 million

    Royalty revenues

    $125 million to $135 million

    Collaboration and license agreement revenues

    Less than $20 million

    Operating expenses and other costs

    Cost of Sales

    $270 million to $300 million

    R&D expenses

    $900 million to $1,000 million

    SG&A expenses

    $650 million to $725 million

    Non-cash expenses1 (primarily attributable to share-based compensation)

    $225 million to $245 million

    1. Non-cash expenses include share-based compensation, depreciation and amortization of intangible assets.

    Conference Call Details

    Seagen management will host a conference call and webcast with supporting slides to discuss its second quarter 2021 and year-to-date financial results and provide an update on business activities. The event will be held today at 1:30 p.m. Pacific Time (PT); 4:30 p.m. Eastern Time (ET). The live event will be simultaneously webcast and available for replay from the Seagen website at www.seagen.com, under the Investors section. Investors may also participate in the conference call by calling 844-763-8274 (domestic) or 412-717-9224 (international). The conference ID is 10157814. Supporting slides are available on the Seagen website at www.seagen.com under the Investors section. A webcast replay will be archived on the Company's website www.seagen.com, under the Investors section.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Forward-Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the Company's 2021 outlook, including anticipated 2021 revenues, costs and expenses; the Company's potential to achieve the noted development and regulatory milestones in 2021 and in future periods; the Company's pipeline; anticipated activities related to the Company's planned and ongoing clinical trials; the potential for the Company's clinical trials to support further development, regulatory submissions and potential marketing approvals in the U.S. and in other countries; the opportunities for, and the therapeutic and commercial potential of ADCETRIS, PADCEV, TUKYSA, tisotumab vedotin and ladiratuzumab vedotin and the Company's other product candidates and those of its licensees and collaborators; anticipated progress with respect to commercialization of TUKYSA in the European Union; the potential to achieve regulatory approvals for, or to commercialize, tisotumab vedotin; the timeline for completing enrollment in randomized cohort K of the EV-103 trial; the potential for data from the EV-103 trial to support registration under the FDA's accelerated approval pathway; the Company's global expansion; potential future milestone payments and royalties under the Company's collaborations; as well as other statements that are not historical fact. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation: the risks that the Company's ADCETRIS, PADCEV and TUKYSA net sales, revenues, expenses, costs, and other financial guidance may not be as expected; risks and uncertainties associated with maintaining or increasing sales of ADCETRIS, PADCEV and TUKYSA due to competition, unexpected adverse events, regulatory action, reimbursement, market adoption by physicians, impacts associated with COVID-19 or other factors; the risk that the Company or its collaborators may be delayed or unsuccessful in planned clinical trial initiations, enrollment in and conduct of clinical trials, obtaining data from clinical trials, planned regulatory submissions, and regulatory approvals in the U.S. and in other countries in each case for a variety of reasons including the difficulty and uncertainty of pharmaceutical product development, negative or disappointing clinical trial results, unexpected adverse events or regulatory actions and the inherent uncertainty associated with the regulatory approval process; the possibility that the Company may encounter challenges in commercializing its therapeutic agents, including with respect to reimbursement, compliance, operational or other matters; risks relating to the Company's collaboration agreements and its ability to achieve progress dependent milestones thereunder; and risks related to the duration and severity of the COVID-19 pandemic and resulting global economic, financial and healthcare system disruptions. More information about the risks and uncertainties faced by the Company is contained under the caption "Risk Factors" included in the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 and the Company's subsequent periodic reports filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise except as required by applicable law.

    Seagen Inc.

    Condensed Consolidated Statements of Operations

    (Unaudited)

    (In thousands, except per share amounts)

     

     

    Three Months Ended June 30,

     

    Six Months Ended June 30,

     

    2021

     

    2020

     

    2021

     

    2020

    Revenues:

     

     

     

     

     

     

     

    Net product sales

    $

    347,338

     

     

    $

    240,465

     

     

    $

    649,926

     

     

    $

    438,979

     

    Royalty revenues

    36,296

     

     

    31,235

     

     

    63,514

     

     

    51,595

     

    Collaboration and license agreement revenues

    4,844

     

     

    6,298

     

     

    7,020

     

     

    21,938

     

    Total revenues

    388,478

     

     

    277,998

     

     

    720,460

     

     

    512,512

     

    Costs and expenses:

     

     

     

     

     

     

     

    Cost of sales

    78,090

     

     

    48,244

     

     

    142,225

     

     

    77,665

     

    Research and development

    234,861

     

     

    198,077

     

     

    465,286

     

     

    393,276

     

    Selling, general and administrative

    165,130

     

     

    125,642

     

     

    324,972

     

     

    247,891

     

    Total costs and expenses

    478,081

     

     

    371,963

     

     

    932,483

     

     

    718,832

     

    Loss from operations

    (89,603

    )

     

    (93,965

    )

     

    (212,023

    )

     

    (206,320

    )

    Investment and other income, net

    5,027

     

     

    72,775

     

     

    6,027

     

     

    16,728

     

    Net loss

    $

    (84,576

    )

     

    $

    (21,190

    )

     

    $

    (205,996

    )

     

    $

    (189,592

    )

    Net loss per share - basic and diluted

    $

    (0.47

    )

     

    $

    (0.12

    )

     

    $

    (1.14

    )

     

    $

    (1.10

    )

    Shares used in computation of per share amounts - basic and diluted

    181,628

     

     

    173,406

     

     

    181,390

     

     

    172,878

     

    Seagen Inc.

    Condensed Consolidated Balance Sheets

    (Unaudited)

    (In thousands)

     

     

    June 30, 2021

     

    December 31, 2020

    Assets

     

     

     

    Cash, cash equivalents and investments

    $

    2,451,612

     

    $

    2,660,250

    Other assets

     

    1,500,546

     

     

    1,340,656

    Total assets

    $

    3,952,158

     

    $

    4,000,906

    Liabilities and Stockholders' Equity

     

     

     

    Accounts payable and accrued liabilities

    $

    433,834

     

    $

    388,138

    Long-term liabilities

     

    127,050

     

     

    124,668

    Stockholders' equity

     

    3,391,274

     

     

    3,488,100

    Total liabilities and stockholders' equity

    $

    3,952,158

     

    $

    4,000,906

     

    View Full Article Hide Full Article
  8. TOKYO and BOTHELL, Wash., July 9, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced the U.S. Food and Drug Administration (FDA) granted PADCEV® (enfortumab vedotin-ejfv) regular approval in the U.S., in addition to approving a new indication for adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. Cisplatin-ineligible patients typically have limited treatment options and a poor prognosis.

    In 2019, the FDA granted accelerated approval for PADCEV for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery, or in a locally advanced or metastatic urothelial cancer setting. The conversion from accelerated approval to regular approval and the label expansion were based on two supplemental Biologics License Applications (sBLAs) reviewed under the Real-Time Oncology Review (RTOR) pilot program.

    "The FDA's decision to convert accelerated approval to regular approval was based on data from the Phase 3 EV-301 trial, which had a primary endpoint of overall survival for patients treated with PADCEV versus chemotherapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "With PADCEV, for the first time, physicians can treat advanced urothelial cancer following treatment with a platinum-containing therapy and immunotherapy using an FDA-approved therapy that has demonstrated an overall survival benefit compared with chemotherapy."

    The EV-301 trial compared PADCEV to chemotherapy in adult patients (n=608) with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. At the time of pre-specified interim analysis, patients who received PADCEV (n=301) in the trial lived a median of 3.9 months longer than those who received chemotherapy (n=307). Median overall survival was 12.9 vs. 9.0 months, respectively [Hazard Ratio=0.70 (95% Confidence Interval [CI]: 0.56, 0.89), p=0.001]. The most common all-grade adverse reactions (≥20%) included rash, fatigue, peripheral neuropathy, alopecia, decreased appetite, diarrhea, pruritus, nausea, constipation, dysgeusia, musculoskeletal pain, dry eye, pyrexia, abdominal pain and anemia.  

    "PADCEV is the first and only FDA-approved therapy for patients with locally advanced or metastatic urothelial cancer who have received immunotherapy and cannot receive cisplatin," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "Because of the FDA's Real-Time Oncology Review, we're able to make PADCEV available as early as possible to these patients, who have limited treatment options due to their age or comorbid conditions."

    Cohort 2 of the EV-201 trial evaluated PADCEV in patients (n=89) with locally advanced or metastatic urothelial cancer who had been previously treated with a PD-1/L1 inhibitor, had not received a platinum-containing chemotherapy in this setting, and were ineligible for cisplatin. After a median follow-up of 16 months, 51 percent of patients who received PADCEV had an objective response [95% CI: 39.8, 61.3] per blinded independent central review, with a median duration of response of 13.8 months [95% CI: 6.4, not reached]. The most common all-grade adverse reactions (≥20%) included rash, peripheral neuropathy, alopecia, fatigue, decreased appetite, anemia, diarrhea, pruritus, weight decreased, nausea, dry eye and dysgeusia.  

    "Almost half of advanced bladder cancer patients cannot receive cisplatin-based chemotherapy. Many of these patients will receive first-line immunotherapy. If their cancer does not respond -- or if it progresses after prior response to immunotherapy -- there is an urgent need for more treatment options as there is currently no standard of care," said Evan Y. Yu, M.D., Division of Oncology, Department of Medicine, University of Washington School of Medicine and a lead investigator for the EV-201 trial, in which all patients were previously treated with immunotherapy. "A new regulatory approval for enfortumab vedotin is an important clinical advance and can help serve this unmet need."

    Please see Important Safety Information including BOXED WARNING at the end of this press release. 

    Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.1 PADCEV is the subject of a robust development program aimed at addressing unmet needs across the continuum of urothelial cancer and in other solid tumors.

    The FDA's RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. The agency's review was also conducted as part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities. Through Project Orbis, health authorities in Australia and Canada are continuing to review data from EV-301 and EV-201 for initial registrations.

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in 608 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies.2 The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters. Results were published in the New England Journal of Medicine. 

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, multi-cohort, multicenter, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (Cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (Cohort 2). The trial enrolled 125 patients in Cohort 1 and 89 patients in Cohort 2 at multiple centers internationally.3 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability. Results of Cohort 2 were published in the Lancet Oncology.

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.4,5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).5 PADCEV is co-developed by Astellas and Seagen.

    BOXED WARNING: SERIOUS SKIN INFECTIONS

    • PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
    • Closely monitor patients for skin reactions.
    • Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
    • Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    U.S. Indication

    PADCEV is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

    • have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum containing chemotherapy, or
    • are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.4

    Important Safety Information 

    Warnings and Precautions  

    Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN, occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. Withhold PADCEV and refer for specialized care for suspected SJS or TEN or for severe (Grade 3) skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN, or for Grade 4 or recurrent Grade 3 skin reactions. 

    Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials, 14% of the 680 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20.3). Hyperglycemia led to discontinuation of PADCEV in 0.6% of patients. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV. 

    Pneumonitis Severe, life-threatening or fatal pneumonitis occurred in patients treated with PADCEV. In clinical trials, 3.1% of the 680 patients treated with PADCEV had pneumonitis of any grade and 0.7% had Grade 3-4. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6). Monitor patients for signs and symptoms indicative of pneumonitis, such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis. 

    Peripheral neuropathy (PN) occurred in 52% of the 680 patients treated with PADCEV in clinical trials, including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without preexisting PN. The median time to onset of Grade ≥2 PN was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN. 

    Ocular disorders were reported in 40% of the 384 patients treated with PADCEV in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders. 

    Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions. 

    Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose. 

    Adverse Reactions  

    Most Common Adverse Reactions, Including Laboratory Abnormalities (≥20%) 

    Rash, aspartate aminotransferase (AST) increased, glucose increased, creatinine increased, fatigue, PN, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase (ALT) increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin. 

    EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy. 

    Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite and fatigue (3% each). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST increased (12%), hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%). 

    EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for platinum-based chemotherapy. 

    Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥3%) were pneumonia, sepsis and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), AST increased and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%) and fatigue (7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST increased (12%), lipase increased (11%), ALT increased (10%), pneumonitis (4%) and infusion site extravasation (1%). 

    Drug Interactions  

    Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors

    Concomitant use with a dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors. 

    Specific Populations 

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose. 

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment. 

    For more information, please see the full Prescribing Information including BOXED WARNING for PADCEV here. 

    About Astellas  

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en

    About Seagen  

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter. 

    About the Astellas and Seagen Collaboration 

    Astellas and Seagen are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings. 

    Astellas Cautionary Notes 

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.  

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice. 

    Seagen Forward Looking Statements 

    Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that utilization and adoption of PADCEV in its additional labeled indication by prescribing physicians may be limited by physician awareness, the extent of reimbursement, impacts related to the COVID-19 pandemic or other factors; and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the failure of ongoing and subsequent clinical trials to establish sufficient efficacy, the risk of adverse events or safety signals or as a result of adverse regulatory actions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. 

    References

    ____________________

    1  World Health Organization, International Agency for Research on Cancer. Globocan 2020 world fact sheet. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed June 29, 2021.

    2 Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021; 10.1056/NEJMoa2035807.

    3 3 Yu EY, Petrylak DP, O'Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicenter, single-arm, phase 2 trial. The Lancet Oncology. 2021: S1470-2045(21)00094-2.

    4 PADCEV [package insert]. Northbrook, Ill.: Astellas Pharma US, Inc.

    5 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

     

    Cision View original content to download multimedia:https://www.prnewswire.com/news-releases/us-fda-grants-regular-approval-and-expands-indication-for-padcev-enfortumab-vedotin-ejfv-for-patients-with-locally-advanced-or-metastatic-urothelial-cancer-301328851.html

    SOURCE Astellas Pharma Inc.

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  9. - Regular Approval Based on Overall Survival Results from Confirmatory EV-301 Trial -

    - First and Only FDA-Approved Therapy for Urothelial Cancer Patients Who Are Cisplatin-Ineligible and Have Previously Received One or More Prior Therapies, Based on Cohort 2 of Pivotal EV-201 Trial -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced the U.S. Food and Drug Administration (FDA) granted PADCEV® (enfortumab vedotin-ejfv) regular approval in the U.S., in addition to approving a new indication for adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received one or more…

    - Regular Approval Based on Overall Survival Results from Confirmatory EV-301 Trial -

    - First and Only FDA-Approved Therapy for Urothelial Cancer Patients Who Are Cisplatin-Ineligible and Have Previously Received One or More Prior Therapies, Based on Cohort 2 of Pivotal EV-201 Trial -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced the U.S. Food and Drug Administration (FDA) granted PADCEV® (enfortumab vedotin-ejfv) regular approval in the U.S., in addition to approving a new indication for adult patients with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. Cisplatin-ineligible patients typically have limited treatment options and a poor prognosis.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210709005414/en/

    PADCEV (enfortumab vedotin-ejfv) 20 mg vial US (Photo: Business Wire)

    PADCEV (enfortumab vedotin-ejfv) 20 mg vial US (Photo: Business Wire)

    In 2019, the FDA granted accelerated approval for PADCEV for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery, or in a locally advanced or metastatic urothelial cancer setting. The conversion from accelerated approval to regular approval and the label expansion were based on two supplemental Biologics License Applications (sBLAs) reviewed under the Real-Time Oncology Review (RTOR) pilot program.

    "The FDA's decision to convert accelerated approval to regular approval was based on data from the Phase 3 EV-301 trial, which had a primary endpoint of overall survival for patients treated with PADCEV versus chemotherapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "With PADCEV, for the first time, physicians can treat advanced urothelial cancer following treatment with a platinum-containing therapy and immunotherapy using an FDA-approved therapy that has demonstrated an overall survival benefit compared with chemotherapy."

    The EV-301 trial compared PADCEV to chemotherapy in adult patients (n=608) with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. At the time of pre-specified interim analysis, patients who received PADCEV (n=301) in the trial lived a median of 3.9 months longer than those who received chemotherapy (n=307). Median overall survival was 12.9 vs. 9.0 months, respectively [Hazard Ratio=0.70 (95% Confidence Interval [CI]: 0.56, 0.89), p=0.001]. The most common all-grade adverse reactions (≥20%) included rash, fatigue, peripheral neuropathy, alopecia, decreased appetite, diarrhea, pruritus, nausea, constipation, dysgeusia, musculoskeletal pain, dry eye, pyrexia, abdominal pain and anemia.

    "PADCEV is the first and only FDA-approved therapy for patients with locally advanced or metastatic urothelial cancer who have received immunotherapy and cannot receive cisplatin," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "Because of the FDA's Real-Time Oncology Review, we're able to make PADCEV available as early as possible to these patients, who have limited treatment options due to their age or comorbid conditions."

    Cohort 2 of the EV-201 trial evaluated PADCEV in patients (n=89) with locally advanced or metastatic urothelial cancer who had been previously treated with a PD-1/L1 inhibitor, had not received a platinum-containing chemotherapy in this setting, and were ineligible for cisplatin. After a median follow-up of 16 months, 51 percent of patients who received PADCEV had an objective response [95% CI: 39.8, 61.3] per blinded independent central review, with a median duration of response of 13.8 months [95% CI: 6.4, not reached]. The most common all-grade adverse reactions (≥20%) included rash, peripheral neuropathy, alopecia, fatigue, decreased appetite, anemia, diarrhea, pruritus, weight decreased, nausea, dry eye and dysgeusia.

    "Almost half of advanced bladder cancer patients cannot receive cisplatin-based chemotherapy. Many of these patients will receive first-line immunotherapy. If their cancer does not respond -- or if it progresses after prior response to immunotherapy -- there is an urgent need for more treatment options as there is currently no standard of care," said Evan Y. Yu, M.D., Division of Oncology, Department of Medicine, University of Washington School of Medicine and a lead investigator for the EV-201 trial, in which all patients were previously treated with immunotherapy. "A new regulatory approval for enfortumab vedotin is an important clinical advance and can help serve this unmet need."

    Please see Important Safety Information including BOXED WARNING at the end of this press release.

    Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.1 PADCEV is the subject of a robust development program aimed at addressing unmet needs across the continuum of urothelial cancer and in other solid tumors.

    The FDA's RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. The agency's review was also conducted as part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities. Through Project Orbis, health authorities in Australia and Canada are continuing to review data from EV-301 and EV-201 for initial registrations.

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in 608 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies.2 The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters. Results were published in the New England Journal of Medicine.

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, multi-cohort, multicenter, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (Cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (Cohort 2). The trial enrolled 125 patients in Cohort 1 and 89 patients in Cohort 2 at multiple centers internationally.3 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability. Results of Cohort 2 were published in the Lancet Oncology.

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.4,5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).5 PADCEV is co-developed by Astellas and Seagen.

    BOXED WARNING: SERIOUS SKIN INFECTIONS

    • PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
    • Closely monitor patients for skin reactions.
    • Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
    • Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    U.S. Indication

    PADCEV is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

    • have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
    • are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.

    Important Safety Information

    Warnings and Precautions

    Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN, occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. Withhold PADCEV and refer for specialized care for suspected SJS or TEN or for severe (Grade 3) skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN, or for Grade 4 or recurrent Grade 3 skin reactions.

    Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials, 14% of the 680 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20.3). Hyperglycemia led to discontinuation of PADCEV in 0.6% of patients. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

    Pneumonitis Severe, life-threatening or fatal pneumonitis occurred in patients treated with PADCEV. In clinical trials, 3.1% of the 680 patients treated with PADCEV had pneumonitis of any grade and 0.7% had Grade 3-4. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6). Monitor patients for signs and symptoms indicative of pneumonitis, such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis.

    Peripheral neuropathy (PN) occurred in 52% of the 680 patients treated with PADCEV in clinical trials, including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without preexisting PN. The median time to onset of Grade ≥2 PN was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN.

    Ocular disorders were reported in 40% of the 384 patients treated with PADCEV in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

    Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

    Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Most Common Adverse Reactions, Including Laboratory Abnormalities (≥20%)

    Rash, aspartate aminotransferase (AST) increased, glucose increased, creatinine increased, fatigue, PN, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase (ALT) increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.

    EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy.

    Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite and fatigue (3% each). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST increased (12%), hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%).

    EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for platinum-based chemotherapy.

    Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥3%) were pneumonia, sepsis and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), AST increased and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%) and fatigue (7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST increased (12%), lipase increased (11%), ALT increased (10%), pneumonitis (4%) and infusion site extravasation (1%).

    Drug Interactions

    Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)

    Concomitant use with a dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

    Specific Populations

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information including BOXED WARNING for PADCEV here.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About the Seagen and Astellas Collaboration

    Seagen and Astellas are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Seagen and Astellas co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that utilization and adoption of PADCEV in its additional labeled indication by prescribing physicians may be limited by physician awareness, the extent of reimbursement, impacts related to the COVID-19 pandemic or other factors; and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the failure of ongoing and subsequent clinical trials to establish sufficient efficacy, the risk of adverse events or safety signals or as a result of adverse regulatory actions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    References


    1 World Health Organization, International Agency for Research on Cancer. Globocan 2020 world fact sheet. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed June 29, 2021.

    2 Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021; 10.1056/NEJMoa2035807.

    3 Yu EY, Petrylak DP, O'Donnell PH, et al. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicenter, single-arm, phase 2 trial. The Lancet Oncology. 2021: S1470-2045(21)00094-2.

    4 PADCEV [package insert]. Northbrook, Ill.: Astellas Pharma US, Inc.

    5 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

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  10. Seagen Inc. (NASDAQ:SGEN) today announced that it will report its second quarter 2021 financial results on Thursday, July 29, 2021 after the close of U.S. financial markets. Following the announcement, Company management will host a conference call and webcast discussion of the results and provide a business update. Access to the event can be obtained as follows:

    Thursday, July 29, 2021

    1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time

    • Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10157814
    • Webcast with slides available at www.seagen.com in the Investors section. A webcast replay will be archived on the Company's website.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and…

    Seagen Inc. (NASDAQ:SGEN) today announced that it will report its second quarter 2021 financial results on Thursday, July 29, 2021 after the close of U.S. financial markets. Following the announcement, Company management will host a conference call and webcast discussion of the results and provide a business update. Access to the event can be obtained as follows:

    Thursday, July 29, 2021

    1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time

    • Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10157814
    • Webcast with slides available at www.seagen.com in the Investors section. A webcast replay will be archived on the Company's website.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

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  11. - Updated Analysis Shows Median Overall Survival for TUKYSA Arm Extended to Two Years, with Benefit Maintained Across All Prespecified Patient Subgroups in HER2CLIMB Trial -

    - Results Further Support TUKYSA as Well-Tolerated Treatment Option That Improves Survival in Patients with Previously Treated Metastatic HER2-Positive Breast Cancer With and Without Brain Metastases -

    Seagen Inc. (NASDAQ:SGEN) today announced that improvements in overall survival (OS) and progression-free survival (PFS) were maintained with long-term follow up from the pivotal HER2CLIMB trial evaluating the addition of TUKYSA® (tucatinib) to trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer (MBC) with and without brain metastases. Data…

    - Updated Analysis Shows Median Overall Survival for TUKYSA Arm Extended to Two Years, with Benefit Maintained Across All Prespecified Patient Subgroups in HER2CLIMB Trial -

    - Results Further Support TUKYSA as Well-Tolerated Treatment Option That Improves Survival in Patients with Previously Treated Metastatic HER2-Positive Breast Cancer With and Without Brain Metastases -

    Seagen Inc. (NASDAQ:SGEN) today announced that improvements in overall survival (OS) and progression-free survival (PFS) were maintained with long-term follow up from the pivotal HER2CLIMB trial evaluating the addition of TUKYSA® (tucatinib) to trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer (MBC) with and without brain metastases. Data from the pre-specified exploratory analysis will be presented (Abstract #1043) as part of the virtual scientific program of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

    The overall survival benefit seen with TUKYSA at the time of the primary analysis was maintained after an additional 15.6 months of follow-up (total of 29.6 months), demonstrating a 5.5-month improvement in median OS (24.7 months (95% CI: 21.6, 28.9) for the TUKYSA regimen vs. 19.2 months (95% CI: 16.4, 21.4) for capecitabine and trastuzumab alone). This benefit continued to be generally consistent across pre-specified patient subgroups.

    "Late-stage, HER2-positive metastatic cancer has proven difficult to treat," said Giuseppe Curigliano, M.D., Ph.D., Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, and Associate Professor of Medical Oncology, University of Milano, Italy. "These data further support that treatment with the tucatinib regimen helps patients live longer compared to trastuzumab and capecitabine alone. These benefits were observed across all prespecified subgroups of patients in the trial, including those with or without brain metastases."

    "These results support the significant impact that a TUKYSA regimen can have for patients with HER2-positive metastatic breast cancer," said Roger D. Dansey, M.D., Chief Medical Officer of Seagen. "The long-term data from the HER2CLIMB trial showed that the survival benefit was sustained with median overall survival longer than that observed at the primary analysis."

    Overall Survival (OS):

    • Median OS in the TUKYSA arm was 24.7 months (95% CI: 21.6, 28.9) compared to median OS of 19.2 months (95% CI: 16.4, 21.4) in the control arm (HR=0.73 [95% CI: 0.59-0.90]; p=0.004).

    Progression Free Survival (PFS):

    • The median PFS in the TUKYSA arm was 7.6 months (95% CI: 6.9, 8.3), compared to median PFS of 4.9 months (95% CI: 4.1, 5.6) in the control arm (HR=00.57 [95% CI: 0.47-0.70]; p<0.00001).

    Safety

    • The safety profile was generally consistent with the primary analysis. The most common adverse events occurring in more than 20 percent of patients who received TUKYSA included diarrhea, palmar-plantar erythrodysaesthesia syndrome, nausea, fatigue, vomiting, decreased appetite, stomatitis, headache, increased aspartate aminotransferase, anemia, increased alanine aminotransferase, and increased blood bilirubin.
    • Grade 3 or greater adverse events occurring in more than five percent of patients in either arm were diarrhea (13.1% TUKYSA vs. 8.6% for the control arm), palmar-plantar erythrodysaethesia syndrome (14.1% vs. 9.1%), fatigue (5.4% vs. 4.1%), and increased alanine aminotransferase (5.7% vs. 0.5%).
    • Discontinuations due to adverse events were infrequent in both arms of the trial, with 5.9 percent in the TUKYSA arm and 4.1 percent in the control arm.

    TUKYSA in combination with trastuzumab and capecitabine was approved by the U.S. Food and Drug Administration (FDA) in April 2020 for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In February 2021, the European Medicines Agency (EMA) and U.K. Medicines and Healthcare products Regulatory Agency (MHRA) each approved TUKYSA in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens. TUKYSA is also approved in Canada, Switzerland, Singapore and Australia.

    In September 2020, Seagen granted Merck, known as MSD outside the U.S. and Canada, exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe.

    About HER2CLIMB

    HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate. Safety data were evaluated throughout the study.1

    About HER2-Positive Breast Cancer

    Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In 2018, more than two million new cases of breast cancer were diagnosed worldwide, including 522,513 in Europe. 2 Between 15 and 20 percent of breast cancer cases are HER2-positive.3 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.3,4,5 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.6,7,8

    About TUKYSA (tucatinib)

    TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.

    U.S. Important Safety Information

    Warnings and Precautions

    • Diarrhea – TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 12% with Grade 3 diarrhea and 0.5% with Grade 4 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.



      If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
    • Hepatotoxicity – TUKYSA can cause severe hepatotoxicity. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 6% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients.



      Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
    • Embryo-Fetal Toxicity – TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential risk to a fetus. Advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during TUKYSA treatment and for at least 1 week after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in ≥2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

    Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%).

    The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

    Lab Abnormalities

    In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

    Drug Interactions

    • Strong CYP3A or Moderate CYP2C8 Inducers: Concomitant use may decrease TUKYSA activity. Avoid concomitant use of TUKYSA.
    • Strong or Moderate CYP2C8 Inhibitors: Concomitant use of TUKYSA with a strong CYP2C8 inhibitor may increase the risk of TUKYSA toxicity; avoid concomitant use. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.
    • CYP3A Substrates: Concomitant use may increase the toxicity associated with a CYP3A substrate. Avoid concomitant use of TUKYSA where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage.
    • P-gp Substrates: Concomitant use may increase the toxicity associated with a P-gp substrate. Consider reducing the dosage of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity.

    Use in Specific Populations

    • Lactation: Advise women not to breastfeed while taking TUKYSA and for at least 1 week after the last dose.
    • Renal Impairment: Use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr < 30 mL/min), because capecitabine is contraindicated in patients with severe renal impairment.
    • Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.

    For more information, please see the full Prescribing Information for TUKYSA here.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of TUKYSA including its efficacy, safety and therapeutic uses, and the potential to make TUKYSA available to patients in Europe. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the possibilities that we may experience delays or setbacks in seeking pricing and reimbursement approvals or otherwise in commercializing TUKYSA in Europe; that adverse events or safety signals may occur; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 filed with the U.S. Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    ____________________

    1 TUKYSA [package insert]. Bothell, WA: Seagen Inc.

    2 Breast. Globocan 2020. World Health Organization. 2020. https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf

    3 Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.

    4 Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu onco­gene. Science. 1987; 235(4785): 177-82.

    5 Breast Cancer HER2 Status. American Cancer Society website. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed March 9, 2020.

    6 Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2019;37:1081-1089.

    7 Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.

    8 Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972-2977.

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  12. Seagen Inc. (NASDAQ:SGEN) today announced that management will participate in a fireside chat at the Goldman Sachs 42nd Annual Global Healthcare Conference on Wednesday, June 9, 2021 at 2:10 p.m. Eastern Time. The presentation will be webcast live and available for replay from Seagen's website at www.seagen.com in the Investors section.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com

    Seagen Inc. (NASDAQ:SGEN) today announced that management will participate in a fireside chat at the Goldman Sachs 42nd Annual Global Healthcare Conference on Wednesday, June 9, 2021 at 2:10 p.m. Eastern Time. The presentation will be webcast live and available for replay from Seagen's website at www.seagen.com in the Investors section.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

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  13. TOKYO and BOTHELL, Wash., May 19, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced updated results from two clinical trials examining PADCEV® (enfortumab vedotin-ejfv) alone (EV-201 Cohort 2) and PADCEV in combination with Merck's (known as MSD outside the United States and Canada) KEYTRUDA® (pembrolizumab) (EV-103 Cohort A) in patients with locally advanced or metastatic urothelial cancer who are not able to receive cisplatin chemotherapy.

    "EV-201 Cohort 2 is the first study to report objective responses in patients with advanced urothelial cancer that progressed following immunotherapy and who have medical conditions that prevent them from receiving cisplatin chemotherapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "The analysis that will be presented at ASCO showed that after a median follow-up of 16 months, many patients continued to benefit from PADCEV – an important finding for these patients, who have very limited treatment options."

    "EV-103 is the first clinical trial to combine the antibody-drug conjugate PADCEV with Merck's

    anti-PD-1 therapy KEYTRUDA in patients newly diagnosed with locally advanced or metastatic urothelial cancer," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "The updated data from EV-103 Cohort A, with two years of follow-up, build upon findings from the initial analysis, showing continued durability for this platinum-free combination."

    Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2 (Abstract 4524)

    Patients in Cohort 2 of EV-201 received prior treatment with an immunotherapy but had not received a platinum-containing chemotherapy in the locally advanced or metastatic setting and were ineligible for cisplatin chemotherapy.

    With a median follow-up of 16 months, 51 percent of patients who received PADCEV had a confirmed objective response [95% Confidence Interval (CI): 39.8, 61.3] per blinded independent central review (the primary endpoint), with 22 percent of patients experiencing a complete response (CR). Median duration of response (DOR) was 13.8 months [95% CI: 6.4, not reached]. Patients lived a median of 6.7 months without cancer progression [progression-free survival (PFS) (95% CI: 5.0-8.3)] and had a median overall survival (OS) of 16.1 months (95% CI: 11.3, 24.1).

    The most common all-grade treatment-related adverse events (TRAEs) were alopecia (51%), peripheral sensory neuropathy (49%) and fatigue (34%), and the most common Grade 3 or greater TRAEs were neutropenia (9%), maculopapular rash (8%) and fatigue (7%). Grade 3 or greater TRAEs of special interest included skin reactions (17%), peripheral neuropathy (8%) and hyperglycemia (6%). Four deaths were previously reported as treatment-related by investigators in patients age 75 years and older with multiple comorbidities.

    The U.S. Food and Drug Administration (FDA) recently granted Priority Review to a supplemental application for PADCEV based on the primary analysis from EV-201 Cohort 2, which was published this month in The Lancet Oncology

    Study EV-103: Update on durability results and long-term outcome of enfortumab vedotin + pembrolizumab in first-line locally advanced or metastatic urothelial carcinoma (la/mUC) (Abstract 4528)

    In the dose-escalation cohort and expansion Cohort A in EV-103, patients were treated with a combination of PADCEV and the anti-PD-1 therapy KEYTRUDA as a first-line treatment for locally advanced or metastatic disease. Participants were ineligible for cisplatin-based chemotherapy, had no prior systemic treatment for locally advanced or metastatic disease, and did not receive adjuvant/neoadjuvant platinum-based therapy within 12 months prior to enrollment.

    The primary outcome measure in this analysis was safety. With a median follow-up of 24.9 months, the longer-term analysis demonstrated a safety profile generally consistent with previous findings, with no new safety signals observed. The most common TRAEs were peripheral sensory neuropathy (55.6%), fatigue (51.1%) and alopecia (48.9%), and the most common Grade 3 or greater TRAEs were increased lipase (17.8%), maculopapular rash (11.1%) and fatigue (11.1%). Grade 3 or greater TRAEs of interest included skin reactions (20%), hyperglycemia (8.9%) and peripheral neuropathy (4.4%). There was one death previously reported as possibly related to study treatment (multiple organ dysfunction syndrome).  

    As previously reported, results demonstrated an objective response rate of 73.3 percent (95% CI: 58.1, 85.4) per investigator assessment, with 15.6 percent of patients experiencing a CR. The median PFS was 12.3 months (95% CI: 8.0, not reached). With longer-term follow-up, the study showed a median DOR of 25.6 months (95% CI: 8.3, not reached) and median OS of 26.1 months (95% CI: 15.7, not reached).

    The FDA granted Breakthrough Therapy designation last year for the PADCEV and KEYTRUDA combination for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.2

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (Cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (Cohort 2). The trial enrolled 128 patients in Cohort 1 and 91 patients in Cohort 2 at multiple centers internationally.1 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

    About the EV-103 Trial

    EV-103 (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of PADCEV alone or in combination, evaluating safety, tolerability and efficacy in muscle invasive urothelial cancer, and in locally advanced or metastatic urothelial cancer in first- or second-line settings.

    The dose-escalation cohort and expansion Cohort A include locally advanced or metastatic urothelial cancer patients who are ineligible for cisplatin-based chemotherapy. Patients were dosed in a 21-day cycle, receiving an intravenous (IV) infusion of enfortumab vedotin on Days 1 and 8 and pembrolizumab on Day 1. At the time of the initial analysis, 45 patients (5 from the dose-escalation cohort and 40 from the dose-expansion Cohort A) with locally advanced and/or metastatic urothelial cancer had been treated with enfortumab vedotin (1.25 mg/kg) plus pembrolizumab in the first-line setting.

    The primary outcome measure of the cohorts included in this analysis is safety. Key secondary objectives related to efficacy include objective response rate, disease control rate, duration of response, progression-free survival and overall survival.

    Additional enrolling cohorts in the EV-103 study include:

    • PADCEV as monotherapy or in combination with pembrolizumab in a first-line setting for locally advanced or metastatic disease, in patients ineligible for cisplatin-based chemotherapy (Cohort K)
    • PADCEV as a monotherapy in muscle-invasive disease (Cohort L)

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.3

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.3,4 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).4 PADCEV is co-developed by Astellas and Seagen.

    PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information 

    Warnings and Precautions 

    Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

    Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. 

    Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C.  In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

    Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

    Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.  

    Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

    Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.  

    Adverse Reactions 

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities 

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%). 

    Drug Interactions 

    Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About the Astellas and Seagen Collaboration

    Astellas and Seagen Inc. are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

    About the Astellas, Seagen and Merck Collaboration

    Astellas and Seagen entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen's and Astellas' PADCEV® (enfortumab vedotin-ejfv) and Merck's KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses, the potential approval by the FDA of the sBLA submission based on the results of cohort 2 of the EV-201 clinical trial and the potential for approval of PADCEV and KEYTRUDA in combination for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that the sBLA submission based on the EV-201 second cohort clinical trial may not be ultimately approved by the FDA in a timely manner or at all; that, even if the PADCEV label is expanded based on the results of the second cohort of the EV-201 clinical trial, the product labeling may not be as broad or desirable as requested or anticipated; and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, adverse regulatory actions or other factors. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    1 American Society of Clinical Oncology. Bladder cancer: introduction (9-2020). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed May 18, 2021.

    2 World Health Organization, International Agency for Research on Cancer. Globocan 2020 world fact sheet. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed May 18, 2021.

    3 PADCEV [package insert] Northbrook, IL: Astellas Pharma Inc

    4 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

     

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/astellas-and-seagen-announce-updated-results-from-two-trials-of-padcev-enfortumab-vedotin-ejfv-in-patients-with-locally-advanced-or-metastatic-urothelial-cancer-not-eligible-for-cisplatin-chemotherapy-301295423.html

    SOURCE Astellas Pharma Inc.

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  14. - Durable Responses Observed in Second Cohort of Patients in Pivotal EV-201 Trial of PADCEV and in Initial First-Line Cohort of the EV-103 Trial Evaluating PADCEV in Combination with KEYTRUDA® (pembrolizumab) -

    - Data to be Presented in Virtual Scientific Program of the 2021 American Society of Clinical Oncology Annual Meeting -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced updated results from two clinical trials examining PADCEV® (enfortumab vedotin-ejfv) alone (EV-201 Cohort 2) and PADCEV in combination with Merck's (known as MSD outside the United States and Canada) KEYTRUDA® (pembrolizumab) (EV-103 Cohort A) in patients with locally advanced or metastatic…

    - Durable Responses Observed in Second Cohort of Patients in Pivotal EV-201 Trial of PADCEV and in Initial First-Line Cohort of the EV-103 Trial Evaluating PADCEV in Combination with KEYTRUDA® (pembrolizumab) -

    - Data to be Presented in Virtual Scientific Program of the 2021 American Society of Clinical Oncology Annual Meeting -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced updated results from two clinical trials examining PADCEV® (enfortumab vedotin-ejfv) alone (EV-201 Cohort 2) and PADCEV in combination with Merck's (known as MSD outside the United States and Canada) KEYTRUDA® (pembrolizumab) (EV-103 Cohort A) in patients with locally advanced or metastatic urothelial cancer who are not able to receive cisplatin chemotherapy.

    "EV-201 Cohort 2 is the first study to report objective responses in patients with advanced urothelial cancer that progressed following immunotherapy and who have medical conditions that prevent them from receiving cisplatin chemotherapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "The analysis that will be presented at ASCO showed that after a median follow-up of 16 months, many patients continued to benefit from PADCEV – an important finding for these patients, who have very limited treatment options."

    "EV-103 is the first clinical trial to combine the antibody-drug conjugate PADCEV with Merck's anti-PD-1 therapy KEYTRUDA in patients newly diagnosed with locally advanced or metastatic urothelial cancer," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "The updated data from EV-103 Cohort A, with two years of follow-up, build upon findings from the initial analysis, showing continued durability for this platinum-free combination."

    Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2 (Abstract 4524)

    Patients in Cohort 2 of EV-201 received prior treatment with an immunotherapy but had not received a platinum-containing chemotherapy in the locally advanced or metastatic setting and were ineligible for cisplatin chemotherapy.

    With a median follow-up of 16 months, 51 percent of patients who received PADCEV had a confirmed objective response [95% Confidence Interval (CI): 39.8, 61.3] per blinded independent central review (the primary endpoint), with 22 percent of patients experiencing a complete response (CR). Median duration of response (DOR) was 13.8 months [95% CI: 6.4, not reached]. Patients lived a median of 6.7 months without cancer progression [progression-free survival (PFS) (95% CI: 5.0-8.3)] and had a median overall survival (OS) of 16.1 months (95% CI: 11.3, 24.1).

    The most common all-grade treatment-related adverse events (TRAEs) were alopecia (51%), peripheral sensory neuropathy (49%) and fatigue (34%), and the most common Grade 3 or greater TRAEs were neutropenia (9%), maculopapular rash (8%) and fatigue (7%). Grade 3 or greater TRAEs of special interest included skin reactions (17%), peripheral neuropathy (8%) and hyperglycemia (6%). Four deaths were previously reported as treatment-related by investigators in patients age 75 years and older with multiple comorbidities.

    The U.S. Food and Drug Administration (FDA) recently granted Priority Review to a supplemental application for PADCEV based on the primary analysis from EV-201 Cohort 2, which was published this month in The Lancet Oncology.

    Study EV-103: Update on durability results and long-term outcome of enfortumab vedotin + pembrolizumab in first-line locally advanced or metastatic urothelial carcinoma (la/mUC) (Abstract 4528)

    In the dose-escalation cohort and expansion Cohort A in EV-103, patients were treated with a combination of PADCEV and the anti-PD-1 therapy KEYTRUDA as a first-line treatment for locally advanced or metastatic disease. Participants were ineligible for cisplatin-based chemotherapy, had no prior systemic treatment for locally advanced or metastatic disease, and did not receive adjuvant/neoadjuvant platinum-based therapy within 12 months prior to enrollment.

    The primary outcome measure in this analysis was safety. With a median follow-up of 24.9 months, the longer-term analysis demonstrated a safety profile generally consistent with previous findings with no new safety signals observed. The most common TRAEs were peripheral sensory neuropathy (55.6%), fatigue (51.1%) and alopecia (48.9%), and the most common Grade 3 or greater TRAEs were increased lipase (17.8%), maculopapular rash (11.1%) and fatigue (11.1%). Grade 3 or greater TRAEs of interest included skin reactions (20%), hyperglycemia (8.9%) and peripheral neuropathy (4.4%). There was one death previously reported as possibly related to study treatment (multiple organ dysfunction syndrome).

    As previously reported, results demonstrated an objective response rate of 73.3 percent (95% CI: 58.1, 85.4) per investigator assessment, with 15.6 percent of patients experiencing a CR. The median PFS was 12.3 months (95% CI: 8.0, not reached). With longer-term follow-up, the study showed a median DOR of 25.6 months (95% CI: 8.3, not reached) and median OS of 26.1 months (95% CI: 15.7, not reached).

    The FDA granted Breakthrough Therapy designation last year for the PADCEV and KEYTRUDA combination for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.2

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (Cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (Cohort 2). The trial enrolled 128 patients in Cohort 1 and 91 patients in Cohort 2 at multiple centers internationally.1 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

    About the EV-103 Trial

    EV-103 (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of PADCEV alone or in combination, evaluating safety, tolerability and efficacy in muscle invasive urothelial cancer, and in locally advanced or metastatic urothelial cancer in first- or second-line settings.

    The dose-escalation cohort and expansion Cohort A include locally advanced or metastatic urothelial cancer patients who are ineligible for cisplatin-based chemotherapy. Patients were dosed in a 21-day cycle, receiving an intravenous (IV) infusion of enfortumab vedotin on Days 1 and 8 and pembrolizumab on Day 1. At the time of the initial analysis, 45 patients (5 from the dose-escalation cohort and 40 from the dose-expansion Cohort A) with locally advanced and/or metastatic urothelial cancer had been treated with enfortumab vedotin (1.25 mg/kg) plus pembrolizumab in the first-line setting.

    The primary outcome measure of the cohorts included in this analysis is safety. Key secondary objectives related to efficacy include objective response rate, disease control rate, duration of response, progression-free survival and overall survival.

    Additional enrolling cohorts in the EV-103 study include:

    • PADCEV as monotherapy or in combination with pembrolizumab in a first-line setting for locally advanced or metastatic disease, in patients ineligible for cisplatin-based chemotherapy (Cohort K)
    • PADCEV as a monotherapy in muscle-invasive disease (Cohort L)

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.3

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.3,4 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).4 PADCEV is co-developed by Astellas and Seagen.

    PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information

    Warnings and Precautions

    Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

    Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

    Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

    Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

    Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

    Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

    Drug Interactions

    Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About the Seagen and Astellas Collaboration

    Seagen and Astellas are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Seagen and Astellas co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

    About the Seagen, Astellas and Merck Collaboration

    Seagen and Astellas entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen's and Astellas' PADCEV® (enfortumab vedotin-ejfv) and Merck's KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses, the potential approval by the FDA of the sBLA submission based on the results of cohort 2 of the EV-201 clinical trial and the potential for approval of PADCEV and KEYTRUDA in combination for patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that the sBLA submission based on the EV-201 second cohort clinical trial may not be ultimately approved by the FDA in a timely manner or at all; that, even if the PADCEV label is expanded based on the results of the second cohort of the EV-201 clinical trial, the product labeling may not be as broad or desirable as requested or anticipated; and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, adverse regulatory actions or other factors. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    ______________________________

    1 American Society of Clinical Oncology. Bladder cancer: introduction (9-2020). https://www.cancer.net/cancer-types/bladdercancer/introduction. Accessed April 28, 2021.

    2 World Health Organization, International Agency for Research on Cancer. Globocan 2020 world fact sheet. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed April 28, 2021.

    3 PADCEV [package insert] Northbrook, IL: Astellas Pharma Inc

    4 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

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  15. -Net Product Sales of $302.6 Million in 1Q21, an Increase of 52 Percent Over 1Q20-

    -Significant Regulatory Progress Across Diverse Oncology Pipeline, Including European Commission Approval of TUKYSA, Multiple Applications Under Review Globally for PADCEV, and FDA Acceptance of Tisotumab Vedotin BLA-

    -Conference Call Today at 4:30 p.m. ET-

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the first quarter and three months ended March 31, 2021. The Company also highlighted ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib) commercial and development accomplishments, as well as progress with its lead pipeline programs to treat cancer.

    "Year-over-year quarterly net product sales growth…

    -Net Product Sales of $302.6 Million in 1Q21, an Increase of 52 Percent Over 1Q20-

    -Significant Regulatory Progress Across Diverse Oncology Pipeline, Including European Commission Approval of TUKYSA, Multiple Applications Under Review Globally for PADCEV, and FDA Acceptance of Tisotumab Vedotin BLA-

    -Conference Call Today at 4:30 p.m. ET-

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the first quarter and three months ended March 31, 2021. The Company also highlighted ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib) commercial and development accomplishments, as well as progress with its lead pipeline programs to treat cancer.

    "Year-over-year quarterly net product sales growth of 52 percent was driven by rapid adoption of our newest products, PADCEV and TUKYSA, in addition to strong sales of ADCETRIS. We continue to project 2021 total net product sales in our territories of approximately $1.3 billion," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seagen. "Looking ahead, we expect continued global progress across the portfolio. This includes TUKYSA launches in Europe following marketing authorizations received in the first quarter. In collaboration with Astellas we are pursuing several PADCEV marketing applications across the United States, Europe, Japan and Latin America. In addition, we are preparing for potential U.S. launch of a fourth drug following FDA acceptance of our tisotumab vedotin BLA submission with Priority Review. We are continuing to deliver cutting-edge innovation and medicines that make a meaningful difference in the lives of cancer patients."

    COMMERCIAL PRODUCTS HIGHLIGHTS

    PADCEV

    • Received European Medicines Agency (EMA) Acceptance of Marketing Authorization Application (MAA): In March 2021, Seagen and Astellas announced that the EMA accepted the PADCEV MAA for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a PD-1/L1 inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. PADCEV will be reviewed under accelerated assessment, which means the EMA's Committee for Medicinal Products for Human Use can shorten the MAA evaluation timeframe.
    • Received FDA Filing Acceptance of Two Supplemental Biologics License Applications (sBLAs): In April 2021, the FDA accepted two PADCEV sBLA submissions for review under the Real-Time Oncology Review pilot program. The applications were granted Priority Review with a target action date of August 17, 2021. The review of both applications will be conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. The first sBLA is based on the phase 3 EV-301 trial and seeks to convert PADCEV's accelerated approval to regular approval. The second sBLA, based on the pivotal trial EV-201's cohort 2, requests an expansion of the current indication to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin.
    • Submitted Several Additional Global Marketing Authorization Applications: In addition to the MAA under review in the European Union (EU), Seagen and Astellas have submitted applications for PADCEV approval in Australia, Canada, Japan, Singapore, Brazil and Switzerland.
    • Reported Positive EV-201 Cohort 2 and EV-301 Results in Patients with Previously Treated Advanced Urothelial Cancer: In February 2021, results were presented from the phase 3 EV-301 trial comparing PADCEV to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The data showed significant improvements in overall and progression-free survival among patients treated with PADCEV compared to those who received chemotherapy. The findings were published in the New England Journal of Medicine and presented during the virtual scientific program of the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU). Data were also presented at ASCO-GU demonstrating durable tumor responses experienced among patients previously treated with immunotherapy in the second cohort of the pivotal EV-201 trial.

    TUKYSA

    • Received Approval in the EU and Great Britain: In February 2021, TUKYSA was approved by the European Commission for use in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens. The approval of TUKYSA is valid in all countries of the EU, as well as Norway, Liechtenstein, Iceland and Northern Ireland. In addition, TUKYSA was granted marketing authorization in Great Britain by the UK Medicines and Healthcare products Regulatory Agency (MHRA) in the same patient population. MHRA had previously granted TUKYSA a Promising Innovative Medicine designation.
    • Started Enrolling Multiple Clinical Trials: In the first quarter of 2021, the first patient was enrolled in two new clinical trials. The phase 3 CompassHER2 RD trial is evaluating TUKYSA in combination with Kadcyla® (trastuzumab emtansine; T-DM1) compared to Kadcyla alone in the adjuvant HER2-positive breast cancer setting. The trial is being conducted by the Alliance for Clinical Trials in Oncology, a U.S. cooperative group. The second is a phase 2 trial evaluating TUKYSA in combination with trastuzumab in various metastatic solid tumors with HER2 alterations.

    ADCETRIS

    • Expect Publication of 5-year Follow-up Results for ECHELON-1: The five-year update of the phase 3 ECHELON-1 clinical trial have been accepted for publication and should be published in the second quarter 2021. Data showed treatment with ADCETRIS in combination with AVD (Adriamycin [doxorubicin], vinblastine and dacarbazine) resulted in superior long-term outcomes when compared to ABVD, which includes bleomycin, in frontline advanced Hodgkin lymphoma.

    PIPELINE HIGHLIGHTS

    • Received FDA Filing Acceptance of Tisotumab Vedotin BLA for Priority Review: In April 2021, Seagen and Genmab announced the FDA had accepted for Priority Review the tisotumab vedotin BLA for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The FDA has set a target action date of October 10, 2021 submission is based on the results of the innovaTV 204 pivotal phase 2 trial, which were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 and published in The Lancet Oncology in April 2021.
    • Presented Data Highlighting Pipeline of Novel Targeted Therapies at the American Association for Cancer Research (AACR) Annual Meeting: In April 2021, Seagen presented preclinical data on three pipeline programs that support the rationale for clinical development. SEA-TGT, an anti-TIGIT antibody using the Company's sugar-engineered antibody (SEA) technology, and two vedotin-based ADCs, SGN-B6A and SGN-STNV, were highlighted. All of the programs are currently in phase 1 clinical trials.

    For additional information on Seagen's pipeline, visit www.seagen.com/science/pipeline.

    FIRST QUARTER 2021 FINANCIAL RESULTS

    Revenues: Total revenues for the first quarter ended March 31, 2021 increased to $332.0 million, compared to $234.5 million for the same period in 2020. Growth over 2020 was driven by higher sales of PADCEV and the addition of TUKYSA to the Company's commercial portfolio. Revenues are composed of the following three components:

    • Net Product Sales:

     

    Three months ended March 31,

    (dollars in millions)

    2021

     

    2020

     

    % Change

    Total Net Product Sales

    $

    302.6

     

     

    $

    198.5

     

     

    52%

    ADCETRIS

    162.6

     

     

    164.1

     

     

    (1)%

    PADCEV

    69.8

     

     

    34.5

     

     

    102%

    TUKYSA

    70.3

     

     

       

    N/A

    Note: Sum of product sales may not equal total net product sales due to rounding.

    • Royalty Revenues: Royalty revenues for the first quarter in 2021 were $27.2 million, compared to $20.4 million for the same period in 2020. Royalty revenues are primarily driven by sales of ADCETRIS outside the U.S. and Canada by Takeda and, to a lesser extent, royalties from sales of Polivy® (polatuzumab vedotin) by Roche and Blenrep® (belantamab mafodotin) by GlaxoSmithKline, which are ADCs that use Seagen technology.
    • Collaboration and License Agreement Revenues: Amounts earned under the Company's product, development and technology collaborations were $2.2 million in the first quarter in 2021, compared to $15.6 million for the same period in 2020. Collaboration revenues for the first quarter of 2020 included a regulatory milestone related to Polivy under the collaboration with Roche.

    Cost of Sales: Cost of sales for the first quarter in 2021 were $64.1 million, compared to $29.4 million for the same period in 2020. The increase was primarily due to the gross profit share with Astellas based on PADCEV sales, which was $32.5 million in the first quarter of 2021, compared to $16.4 million for the same period in 2020. The increase in cost of sales also reflected amortization of acquired in-process technology costs that began with the approval of TUKYSA in April 2020, and third-party royalties owed for ADCETRIS, PADCEV and TUKYSA net product sales, in addition to cost of products sold.

    Research and Development (R&D) Expenses: R&D expenses for the first quarter in 2021 were $230.4 million, compared to $195.2 million for the same period in 2020. The increase in 2021 primarily reflected continued investment in the Company's pipeline to evaluate new potential indications for the Company's commercial drugs and to advance novel product candidates and technologies.

    Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the first quarter in 2021 were $159.8 million, compared to $122.2 million for the same period in 2020. The increase was primarily attributed to increased field sales personnel and external spend to support our recently commercialized products, PADCEV and TUKYSA, and higher infrastructure costs to support our continued growth in the U.S. and Europe.

    Non-cash, share-based compensation expense for the first three months of 2021 was $38.2 million, compared to $33.6 million for the same period in 2020.

    Net Loss: Net loss for the first quarter of 2021 was $121.4 million, or $0.67 per diluted share, compared to net loss of $168.4 million, or $0.98 per diluted share, for the first quarter of 2020. Net loss in the first quarter of 2020 included a non-cash net investment loss of $59.1 million primarily associated with Seagen's common stock holding in Immunomedics, which was marked-to-market.

    Cash and Investments: As of March 31, 2021, Seagen had $2.5 billion in cash and investments.

    2021 FINANCIAL OUTLOOK

    Seagen anticipates 2021 revenues, operating expenses and other costs to be in the ranges shown in the table below, unchanged from the Company's previous financial guidance provided on February 11, 2021.

    Revenues

    ADCETRIS net product sales

    $675 million to $700 million

    PADCEV net product sales

    $310 million to $325 million

    TUKYSA net product sales

    $300 million to $315 million

    Royalty revenues

    $125 million to $135 million

    Collaboration and license agreement revenues

    Less than $20 million

    Operating expenses and other costs

    Cost of Sales

    $270 million to $300 million

    R&D expenses

    $900 million to $1,000 million

    SG&A expenses

    $650 million to $725 million

    Non-cash expenses1 (primarily attributable to

    share-based compensation)

    $225 million to $245 million

    1. Non-cash expenses include share-based compensation, depreciation and amortization of intangible assets.

    Conference Call Details

    Seagen management will host a conference call and webcast with supporting slides to discuss its first quarter 2021 and year-to-date financial results and provide an update on business activities. The event will be held today at 1:30 p.m. Pacific Time (PT); 4:30 p.m. Eastern Time (ET). The live event will be simultaneously webcast and available for replay from the Seagen website at www.seagen.com, under the Investors section. Investors may also participate in the conference call by calling 844-763-8274 (domestic) or 412-717-9224 (international). The conference ID is 10153242. Supporting slides are available on the Seagen website at www.seagen.com under the Investors section. A webcast replay will be archived on the Company's website www.seagen.com, under the Investors section.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Forward-Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the Company's 2020 outlook, including anticipated 2020 revenues, costs and expenses; the Company's potential to achieve the noted development and regulatory milestones in 2020 and in future periods; the Company's pipeline; anticipated activities related to the Company's planned and ongoing clinical trials; the potential for the Company's clinical trials to support further development, regulatory submissions and potential marketing approvals in the U.S. and in other countries; the opportunities for, and the therapeutic and commercial potential of ADCETRIS, PADCEV, TUKYSA, tisotumab vedotin and ladiratuzumab vedotin and the Company's other product candidates and those of its licensees and collaborators; the potential to submit a BLA for accelerated approval of tisotumab vedotin; the potential for data from the EV-301 and EV-201 cohort 2 clinical trials to support additional regulatory approvals of PADCEV; the potential for the approval of TUKYSA by the EMA; the Company's global expansion; potential future milestone payments and royalties under the Company's collaborations; as well as other statements that are not historical fact. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation: the risks that the Company's ADCETRIS, PADCEV and TUKYSA net sales, revenues, expenses, costs, and other financial guidance may not be as expected; risks and uncertainties associated with maintaining or increasing sales of ADCETRIS, PADCEV and TUKYSA due to competition, unexpected adverse events, regulatory action, reimbursement, market adoption by physicians, impacts associated with COVID-19 or other factors; the risk that the Company or its collaborators may be delayed or unsuccessful in planned clinical trial initiations, enrollment in and conduct of clinical trials, obtaining data from clinical trials, planned regulatory submissions, and regulatory approvals in the U.S. and in other countries in each case for a variety of reasons including the difficulty and uncertainty of pharmaceutical product development, negative or disappointing clinical trial results, unexpected adverse events or regulatory actions and the inherent uncertainty associated with the regulatory approval process; the possibility that the Company may encounter challenges in commercializing its therapeutic agents outside of the United States, including with respect to reimbursement, compliance, operational or other matters; risks relating to the Company's collaboration agreements and its ability to achieve progress dependent milestones thereunder; and risks related to the duration and severity of the COVID-19 pandemic and resulting global economic, financial and healthcare system disruptions. More information about the risks and uncertainties faced by the Company is contained under the caption "Risk Factors" included in the Company's Annual Report on Form 10-K for the year ended December 31, 2020 and the Company's subsequent periodic reports filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise except as required by applicable law.

    Seagen Inc.

    Condensed Consolidated Statements of Operations

    (Unaudited)

    (In thousands, except per share amounts)

     

     

    Three Months Ended March 31,

     

    2021

     

     

    2020

     

    Revenues:

     

     

     

    Net product sales

    $

    302,588

     

     

     

    $

    198,514

     

     

    Royalty revenues

    27,219

     

     

     

    20,360

     

     

    Collaboration and license agreement revenues

    2,176

     

     

     

    15,640

     

     

    Total revenues

    331,983

     

     

     

    234,514

     

     

    Costs and expenses:

     

     

     

    Cost of sales

    64,135

     

     

     

    29,421

     

     

    Research and development

    230,426

     

     

     

    195,199

     

     

    Selling, general and administrative

    159,842

     

     

     

    122,249

     

     

    Total costs and expenses

    454,403

     

     

     

    346,869

     

     

    Loss from operations

    (122,420

    )

     

     

    (112,355

    )

     

    Investment and other income (loss), net

    1,000

     

     

     

    (56,047

    )

     

    Net loss

    $

    (121,420

    )

     

     

    $

    (168,402

    )

     

    Net loss per share - basic and diluted

    $

    (0.67

    )

     

     

    $

    (0.98

    )

     

    Shares used in computation of per share amounts - basic and diluted

    181,150

     

     

     

    172,350

     

     

    Seagen Inc.

    Condensed Consolidated Balance Sheets

    (Unaudited)

    (In thousands)

     

     

    March 31, 2021

     

    December 31, 2020

    Assets

     

     

     

    Cash, cash equivalents and investments

    $

    2,531,156

     

     

    $

    2,660,250

     

    Other assets

    1,411,829

     

     

    1,340,656

     

    Total assets

    $

    3,942,985

     

     

    $

    4,000,906

     

    Liabilities and Stockholders' Equity

     

     

     

    Accounts payable and accrued liabilities

    $

    389,616

     

     

    $

    388,138

     

    Long-term liabilities

    128,745

     

     

    124,668

     

    Stockholders' equity

    3,424,624

     

     

    3,488,100

     

    Total liabilities and stockholders' equity

    $

    3,942,985

     

     

    $

    4,000,906

     

     

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  16. - Data to be Presented Highlight Significant Progress Across Several Tumor Types -

    Seagen Inc. (NASDAQ:SGEN) today announced the presentation of new data from its growing pipeline of marketed and investigational therapies at the virtual scientific program of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, to be held June 4-8.

    "Emerging data and the breadth of our clinical development programs continue to illustrate progress across our oncology portfolio, highlighting the company's research efforts in multiple cancers with a high unmet need," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Notably, we are looking forward to sharing updated results of the EV-103 and EV-201 clinical trials for PADCEV® (enfortumab…

    - Data to be Presented Highlight Significant Progress Across Several Tumor Types -

    Seagen Inc. (NASDAQ:SGEN) today announced the presentation of new data from its growing pipeline of marketed and investigational therapies at the virtual scientific program of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, to be held June 4-8.

    "Emerging data and the breadth of our clinical development programs continue to illustrate progress across our oncology portfolio, highlighting the company's research efforts in multiple cancers with a high unmet need," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Notably, we are looking forward to sharing updated results of the EV-103 and EV-201 clinical trials for PADCEV® (enfortumab vedotin-ejfv) in locally advanced or metastatic urothelial cancer and additional data from the HER2CLIMB trial of TUKYSA® (tucatinib) in previously treated HER2+ metastatic breast cancer patients."

    Key data to be presented include:

    Abstract Title

    Abstract #

    Presentation type

    Lead Author

    PADCEV® (enfortumab vedotin-ejfv)

    Study EV-103: Update on durability results and long-term outcome of enfortumab vedotin + pembrolizumab in first line locally advanced or metastatic urothelial carcinoma (la/mUC)

    4528

    Poster Presentation

    T. Friedlander

    Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2

    4524

    Poster Presentation

    B. McGregor

    Quality of life, functioning, and symptoms in patients with previously treated locally advanced or metastatic urothelial carcinoma from EV-301: A randomized Phase 3 trial of enfortumab vedotin vs chemotherapy

    4539

    Poster Presentation

    R. Mamtani

    KEYNOTE-B15/EV-304: Randomized Phase 3 study of perioperative enfortumab vedotin plus pembrolizumab versus chemotherapy in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC)

    TPS4587

    Poster Presentation

    C. Hoimes

    TUKYSA® (tucatinib)

    Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB)

    1043

    Poster Presentation

    G. Curigliano

    Pharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer

    1044

    Poster Presentation

    E. Stringer-Reasor

    SGNTUC-019: Phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations (trial in progress)

    TPS3151

    Poster Presentation

    T. Stinchcombe

    HER2CLIMB-04: Phase 2 open label trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ unresectable locally advanced or metastatic breast cancer with and without brain metastases (trial in progress)

    TPS1097

    Poster Presentation

    I. Krop

    A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer

    TPS595

    Poster Presentation

    C. O'Sullivan

    ADCETRIS® (brentuximab vedotin)

    Brentuximab vedotin with chemotherapy in adolescents and young adults (AYAs) with stage III or IV Hodgkin lymphoma: A subgroup analysis from the Phase 3 Echelon-1 study

    7528

    Poster Presentation

    H. Crosswell

    Brentuximab vedotin in combination with lenalidomide and rituximab in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (trial in progress)

    TPS7571

    Poster Presentation

    N. Bartlett

    Tisotumab vedotin

    Tisotumab vedotin vs investigator's choice chemotherapy in second- or third-Line recurrent or metastatic cervical cancer (innovaTV 301/ENGOT-cx12/GOG 3057, trial in progress)

    TPS5596

    Poster Presentation

    I. Vergote

    Early Pipeline

    SGNTGT-001: A Phase 1 study of SEA-TGT, an effector-function enhanced monoclonal antibody (mAb), in advanced malignancies (trial in progress)

    TPS2657

    Poster Presentation

    E. Garralda

    A Phase 1 study of SGN-B6A, an antibody-drug conjugate targeting Integrin beta-6, in patients with advanced solid tumors (SGNB6A-001, trial in progress)

    TPS3144

    Poster Presentation

    A. Patnaik

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Forward-Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the company's pipeline and the therapeutic potential of PADCEV, TUKYSA, ADCETRIS, tisotumab vedotin, SEA-TGT and SGN-B6A, including their efficacy, safety and potential therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the difficulty and uncertainty of pharmaceutical product development, including the risks that the company may experience delays in its clinical trials or otherwise experience failures or setbacks in its clinical development programs due to lack of efficacy, adverse events or other factors, and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

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  17. TOKYO and BOTHELL, Wash., April 19, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced the U.S. Food and Drug Administration (FDA) filed two supplemental Biologics License Application (sBLA) submissions for PADCEV® (enfortumab vedotin-ejfv) for review as part of the Real-Time Oncology Review (RTOR) pilot program. The applications were granted Priority Review, with a target action date of August 17, 2021. The review of both applications will also be conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. 

    The FDA's RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. Project Orbis provides a framework for concurrent submission and review of oncology drugs among participating international partners. The first sBLA is based on the phase 3 EV-301 trial and seeks to convert PADCEV's accelerated approval to regular approval. The second sBLA, based on the pivotal trial EV-201's cohort 2, requests an expansion of the current indication to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and are ineligible for cisplatin. Results from EV-301 were published in the New England Journal of Medicine. Results from EV-301 and EV-201 cohort 2 were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium.

    "With our recent regulatory submissions, we intend to provide the highest level of clinical evidence supporting PADCEV use – overall survival data from a randomized phase 3 trial – and expand availability in multiple countries where there is unmet medical need," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas.

    "These FDA filings, along with regulatory submissions outside of the United States under our collaboration with Astellas, are important steps in our shared goal of bringing PADCEV to more patients with advanced urothelial cancer," said Roger Dansey, M.D., Chief Medical Officer of Seagen.

    Health authorities in Australia and Canada will evaluate data from EV-301 and EV-201 for initial registrations under Project Orbis. In March, the companies announced regulatory submissions in Japan and the European Union.

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.2

    In 2019, PADCEV received accelerated approval in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic urothelial cancer setting. PADCEV is currently only approved for use in the U.S.

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and a platinum-based therapy.3 The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.  

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.4 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

    PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information 

    Warnings and Precautions 

    Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

    Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. 

    Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C.  In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

    Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

    Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.  

    Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

    Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.  

    Adverse Reactions 

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities 

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%). 

    Drug Interactions 

    Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About the Astellas and Seagen Collaboration

    Astellas and Seagen are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the potential conversion of PADCEV's current accelerated approval in the U.S. to regular approval and the potential expansion of the current PADCEV label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin; the potential to obtain regulatory approvals in Japan, the European Union, Australia and Canada; and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that the sBLA submissions based on the EV-301 and EV-201 second cohort clinical trials may not be  ultimately approved by the FDA in a timely manner or at all; that the results of the EV-301 clinical trial may not be sufficient to convert PADCEV's accelerated approval in the U.S. to regular approval and that the results of the second cohort of the EV-201 clinical trial may not be sufficient to support the requested label expansion; that, even if PADCEV receives regular approval and even if the PADCEV label is expanded based on the results of the second cohort of the EV-201 clinical trial, the product labeling may not be as broad or desirable as requested or anticipated; and that  regulatory approvals of PADCEV in Japan, the European Union, Australia and Canada may not be obtained or may not be obtained with product labeling that is as broad or desirable as requested or anticipated, and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, adverse regulatory actions or other factors. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    1 American Society of Clinical Oncology. Bladder cancer: introduction (9-2020). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed April 13, 2021.

    2 World Health Organization, International Agency for Research on Cancer. Globocan 2020 world fact sheet. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed April 13, 2021.

    3 Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021; 10.1056/NEJMoa2035807.

    4 Balar AV, McGregor BA, Rosenberg JE, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors [abstract]. In 2021 Genitourinary Cancers Symposium; 2021 Feb 11-13; Alexandria, VA. ASCO GU; 2021. Abstract 394.

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/astellas-and-seagen-announce-us-fda-acceptance-of-two-supplemental-biologics-license-applications-for-padcev-enfortumab-vedotin-ejfv-in-locally-advanced-or-metastatic-urothelial-cancer-301271032.html

    SOURCE Astellas Pharma Inc.

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  18. - Priority Review Granted with Action Date of August 17 -

    - Australia and Canada Regulators Will Review Applications as Part of FDA's Project Orbis -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced the U.S. Food and Drug Administration (FDA) filed two supplemental Biologics License Application (sBLA) submissions for PADCEV® (enfortumab vedotin-ejfv) for review as part of the Real-Time Oncology Review (RTOR) pilot program. The applications were granted Priority Review, with a target action date of August 17, 2021. The review of both applications will also be conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence.

    The FDA's RTOR…

    - Priority Review Granted with Action Date of August 17 -

    - Australia and Canada Regulators Will Review Applications as Part of FDA's Project Orbis -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced the U.S. Food and Drug Administration (FDA) filed two supplemental Biologics License Application (sBLA) submissions for PADCEV® (enfortumab vedotin-ejfv) for review as part of the Real-Time Oncology Review (RTOR) pilot program. The applications were granted Priority Review, with a target action date of August 17, 2021. The review of both applications will also be conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence.

    The FDA's RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. Project Orbis provides a framework for concurrent submission and review of oncology drugs among participating international partners. The first sBLA is based on the phase 3 EV-301 trial and seeks to convert PADCEV's accelerated approval to regular approval. The second sBLA, based on the pivotal trial EV-201's cohort 2, requests an expansion of the current indication to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and are ineligible for cisplatin. Results from EV-301 were published in the New England Journal of Medicine. Results from EV-301 and EV-201 cohort 2 were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium.

    "With our recent regulatory submissions, we intend to provide the highest level of clinical evidence supporting PADCEV use – overall survival data from a randomized phase 3 trial – and expand availability in multiple countries where there is unmet medical need," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas.

    "These FDA filings, along with regulatory submissions outside of the United States under our collaboration with Astellas, are important steps in our shared goal of bringing PADCEV to more patients with advanced urothelial cancer," said Roger Dansey, M.D., Chief Medical Officer of Seagen.

    Health authorities in Australia and Canada will evaluate data from EV-301 and EV-201 for initial registrations under Project Orbis. In March, the companies announced regulatory submissions in Japan and the European Union.

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.2

    In 2019, PADCEV received accelerated approval in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic urothelial cancer setting. PADCEV is currently only approved for use in the U.S.

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and a platinum-based therapy.3 The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.4 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

    PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information

    Warnings and Precautions

    Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

    Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement.

    Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

    Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

    Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

    Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

    Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

    Drug Interactions

    Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About the Astellas and Seagen Collaboration

    Astellas and Seagen are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the potential conversion of PADCEV's current accelerated approval in the U.S. to regular approval and the potential expansion of the current PADCEV label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin; the potential to obtain regulatory approvals in Japan, the European Union, Australia and Canada; and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that the sBLA submissions based on the EV-301 and EV-201 second cohort clinical trials may not be ultimately approved by the FDA in a timely manner or at all; that the results of the EV-301 clinical trial may not be sufficient to convert PADCEV's accelerated approval in the U.S. to regular approval and that the results of the second cohort of the EV-201 clinical trial may not be sufficient to support the requested label expansion; that, even if PADCEV receives regular approval and even if the PADCEV label is expanded based on the results of the second cohort of the EV-201 clinical trial, the product labeling may not be as broad or desirable as requested or anticipated; and that regulatory approvals of PADCEV in Japan, the European Union, Australia and Canada may not be obtained or may not be obtained with product labeling that is as broad or desirable as requested or anticipated, and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, adverse regulatory actions or other factors. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    1 American Society of Clinical Oncology. Bladder cancer: introduction (9-2020). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed April 13, 2021.

    2 World Health Organization, International Agency for Research on Cancer. Globocan 2020 world fact sheet. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed April 13, 2021.

    3 Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021; 10.1056/NEJMoa2035807.

    4 Balar AV, McGregor BA, Rosenberg JE, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors [abstract]. In 2021 Genitourinary Cancers Symposium; 2021 Feb 11-13; Alexandria, VA. ASCO GU; 2021. Abstract 394.

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  19. Company Announcement

    • FDA action date is Oct 10, 2021
    • BLA submission supported by positive pivotal innovaTV 204 trial results presented at the European Society of Medical Oncology Virtual Congress 2020

    COPENHAGEN, Denmark and BOTHELL, Wash.; April 09, 2021 – Genmab A/S (NASDAQ:GMAB) and Seagen Inc. (NASDAQ:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking accelerated approval for tisotumab vedotin. This BLA requests FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target…

    Company Announcement

    • FDA action date is Oct 10, 2021
    • BLA submission supported by positive pivotal innovaTV 204 trial results presented at the European Society of Medical Oncology Virtual Congress 2020

    COPENHAGEN, Denmark and BOTHELL, Wash.; April 09, 2021 – Genmab A/S (NASDAQ:GMAB) and Seagen Inc. (NASDAQ:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking accelerated approval for tisotumab vedotin. This BLA requests FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of Oct 10, 2021. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor (TF), a cell-surface protein expressed on multiple solid tumors including cervical cancer, and is associated with tumor growth, angiogenesis, metastasis and poor prognosis.1

    "We are pleased that the tisotumab vedotin BLA has been accepted with Priority Review by the FDA as there is an unmet need for effective therapies for women with recurrent or metastatic cervical cancer, who have disease progression on or after chemotherapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "This is an important milestone for Genmab as it brings us closer to our goal of bringing differentiated therapies to patients and transforming cancer treatment."

    The FDA's filing of the tisotumab vedotin BLA with Priority Review marks an important step forward for this ADC as a potential treatment for patients with recurrent or metastatic cervical cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "We are collaborating closely with the FDA throughout the review process to make this important therapy available to patients."

    The BLA for tisotumab vedotin was submitted in February 2021. The submission is based on the results of the innovaTV 204 pivotal phase 2 single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent or metastatic cervical cancer. These data were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

    About Cervical Cancer

    Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with invasive cervical cancer in the U.S. in 2020, with approximately 4,200 deaths.2 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.3 Routine medical examinations and human papillomavirus (HPV) vaccines have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic. Current therapies for previously treated recurrent or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent with median overall survival ranging from 6.0 to 9.4 months.4-10

    About the innovaTV 204 Trial

    The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab. Additionally, patients were eligible if they had received up to two prior lines of therapy in the recurrent or metastatic setting. In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the U.S. and Europe. The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review. Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

    The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the Gynecologic Oncology Group (GOG) Foundation. For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

    About Tisotumab Vedotin

    Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab's fully human monoclonal antibody specific for tissue factor and Seagen's ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a cell-surface protein and associated with tumor growth, angiogenesis, metastasis and poor prognosis.1 Based on its elevated expression in multiple solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

    Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial called innovaTV 301 versus investigator's choice of chemotherapy in recurrent or metastatic cervical cancer. The primary endpoint is overall survival and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability. Enrollment is ongoing and the study is intended to support global registrations. In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer, and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three-week dosing schedule. More information about the innovaTV 301 clinical trial, including enrolling sites, as well as other ongoing clinical trials is available at www.clinicaltrials.gov.

    About Genmab

    Genmab is an international biotechnology company with a core purpose to improve the lives of patients with cancer. Founded in 1999, Genmab is the creator of multiple approved antibody therapeutics that are marketed by its partners. The company aims to create, develop and commercialize differentiated therapies by leveraging next-generation antibody technologies, expertise in antibody biology, translational research and data sciences and strategic partnerships. To create novel therapies, Genmab utilizes its next-generation antibody technologies, which are the result of its collaborative company culture and a deep passion for innovation. Genmab's proprietary pipeline consists of modified antibody candidates, including bispecific T-cell engagers and next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates. The company is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com.



    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Contact

    Genmab A/S:  

    Marisol Peron, Senior Vice President, Global Investor Relations & Communications

    T: +1 609 524 0065; E: mmp@genmab.com

    For Investor Relations:

    Andrew Carlsen, Vice President, Head of Investor Relations

    T: +45 3377 9558; E: acn@genmab.com

    Seagen:

    Media and Investors:

    Peggy Pinkston, Senior Vice President, Investor Relations

    (425) 527-4160

    ppinkston@seagen.com

    Genmab Forward Looking Statements

    This Company Announcement contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab's most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab's most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.



    Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo®; HuMax®; DuoBody®; DuoBody in combination with the DuoBody logo®; HexaBody®; HexaBody in combination with the HexaBody logo®; DuoHexaBody®; HexElect®; and UniBody®. Kesimpta® is a trademark of Novartis AG or its affiliates. DARZALEX® and DARZALEX FASPRO® are trademarks of Johnson & Johnson. TEPEZZA® is a trademark of Horizon Therapeutics Ireland DAC.

    Seagen Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy based on the results of the innovaTV 204 trial, the timing of any potential FDA approval and the therapeutic potential of tisotumab vedotin. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the possibility that the Biologics License Application submission based on the innovaTV 204 trial may not be ultimately approved by the FDA in a timely manner or at all or with the requested label; that subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the Company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    1 Rondon et al. Semin Thromb Hemost 2019; 45:396–412.

    2 National Cancer Institute SEER. "Cancer Stat Facts: Cervix Uteri Cancer." Available at https://seer.cancer.gov/statfacts/html/cervix.html. Last accessed April 2020.

    3 Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 countries https://www.iarc.fr/news-events/global-cancer-statistics-2018-globocan-estimates-of-incidence-and-mortality-worldwide-for-36-cancers-in-185-countries/.

    4 Miller et al., Gynecol Oncol 2008; 110:65.

    5 Bookman et al., Gynecol Oncol 2000; 77:446.

    6 Garcia et al., Am J Clin Oncol 2007; 30:428.

    7 Monk et al., J Clin Oncol 2009; 27:1069.

    8 Santin et al., Gynecol Oncol 2011; 122:495.

    9 Schilder et al., Gynecol Oncol 2005; 96:103

    10 Chung HC et al. J Clin Oncol 2019; 37:1470.



    Company Announcement no. 26

    CVR no. 2102 3884

    LEI Code 529900MTJPDPE4MHJ122

    Genmab A/S

    Kalvebod Brygge 43

    1560 Copenhagen V

    Denmark

    Attachment



    Primary Logo

    View Full Article Hide Full Article
    • FDA action date is Oct 10, 2021
    • BLA submission supported by positive pivotal innovaTV 204 trial results presented at the European Society of Medical Oncology Virtual Congress 2020

    Genmab A/S (NASDAQ:GMAB) and Seagen Inc. (NASDAQ:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking accelerated approval for tisotumab vedotin. This BLA requests FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of Oct 10, 2021. Tisotumab vedotin is an investigational…

    • FDA action date is Oct 10, 2021
    • BLA submission supported by positive pivotal innovaTV 204 trial results presented at the European Society of Medical Oncology Virtual Congress 2020

    Genmab A/S (NASDAQ:GMAB) and Seagen Inc. (NASDAQ:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) seeking accelerated approval for tisotumab vedotin. This BLA requests FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of Oct 10, 2021. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor (TF), a cell-surface protein expressed on multiple solid tumors including cervical cancer, and is associated with tumor growth, angiogenesis, metastasis and poor prognosis.1

    "We are pleased that the tisotumab vedotin BLA has been accepted with Priority Review by the FDA as there is an unmet need for effective therapies for women with recurrent or metastatic cervical cancer, who have disease progression on or after chemotherapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "This is an important milestone for Genmab as it brings us closer to our goal of bringing differentiated therapies to patients and transforming cancer treatment."

    The FDA's filing of the tisotumab vedotin BLA with Priority Review marks an important step forward for this ADC as a potential treatment for patients with recurrent or metastatic cervical cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "We are collaborating closely with the FDA throughout the review process to make this important therapy available to patients."

    The BLA for tisotumab vedotin was submitted in February 2021. The submission is based on the results of the innovaTV 204 pivotal phase 2 single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent or metastatic cervical cancer. These data were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

    About Cervical Cancer

    Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with invasive cervical cancer in the U.S. in 2020, with approximately 4,200 deaths.2 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.3 Routine medical examinations and human papillomavirus (HPV) vaccines have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic. Current therapies for previously treated recurrent or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent with median overall survival ranging from 6.0 to 9.4 months.4-10

    About the innovaTV 204 Trial

    The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab. Additionally, patients were eligible if they had received up to two prior lines of therapy in the recurrent or metastatic setting. In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the U.S. and Europe. The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review. Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

    The study was conducted by Genmab in collaboration with Seagen, European Network of Gynaecological Oncological Trial Groups (ENGOT) and the Gynecologic Oncology Group (GOG) Foundation. For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

    About Tisotumab Vedotin

    Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab's fully human monoclonal antibody specific for tissue factor and Seagen's ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a cell-surface protein and associated with tumor growth, angiogenesis, metastasis and poor prognosis.1 Based on its elevated expression in multiple solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

    Tisotumab vedotin is being evaluated in a global phase 3, randomized clinical trial called innovaTV 301 versus investigator's choice of chemotherapy in recurrent or metastatic cervical cancer. The primary endpoint is overall survival and secondary endpoints include progression-free survival, duration of response, objective response rate, safety and tolerability. Enrollment is ongoing and the study is intended to support global registrations. In addition, tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in recurrent or metastatic cervical cancer, ovarian cancer, and other solid tumors and in combination with commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three-week dosing schedule. More information about the innovaTV 301 clinical trial, including enrolling sites, as well as other ongoing clinical trials is available at www.clinicaltrials.gov.

    About Genmab

    Genmab is an international biotechnology company with a core purpose to improve the lives of patients with cancer. Founded in 1999, Genmab is the creator of multiple approved antibody therapeutics that are marketed by its partners. The company aims to create, develop and commercialize differentiated therapies by leveraging next-generation antibody technologies, expertise in antibody biology, translational research and data sciences and strategic partnerships. To create novel therapies, Genmab utilizes its next-generation antibody technologies, which are the result of its collaborative company culture and a deep passion for innovation. Genmab's proprietary pipeline consists of modified antibody candidates, including bispecific T-cell engagers and next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates. The company is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Genmab Forward Looking Statements

    This Company Announcement contains forward looking statements. The words "believe", "expect", "anticipate", "intend" and "plan" and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab's most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab's most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

    Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo®; HuMax®; DuoBody®; DuoBody in combination with the DuoBody logo®; HexaBody®; HexaBody in combination with the HexaBody logo®; DuoHexaBody®; HexElect®; and UniBody®. Kesimpta® is a trademark of Novartis AG or its affiliates. DARZALEX® and DARZALEX FASPRO® are trademarks of Johnson & Johnson. TEPEZZA® is a trademark of Horizon Therapeutics Ireland DAC.

    Seagen Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential FDA approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy based on the results of the innovaTV 204 trial, the timing of any potential FDA approval and the therapeutic potential of tisotumab vedotin. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the possibility that the Biologics License Application submission based on the innovaTV 204 trial may not be ultimately approved by the FDA in a timely manner or at all or with the requested label; that subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the Company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    1 Rondon et al. Semin Thromb Hemost 2019; 45:396–412.

    2 National Cancer Institute SEER. "Cancer Stat Facts: Cervix Uteri Cancer." Available at https://seer.cancer.gov/statfacts/html/cervix.html. Last accessed April 2020.

    3 Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 countries https://www.iarc.fr/news-events/global-cancer-statistics-2018-globocan-estimates-of-incidence-and-mortality-worldwide-for-36-cancers-in-185-countries/.

    4 Miller et al., Gynecol Oncol 2008; 110:65.

    5 Bookman et al., Gynecol Oncol 2000; 77:446.

    6 Garcia et al., Am J Clin Oncol 2007; 30:428.

    7 Monk et al., J Clin Oncol 2009; 27:1069.

    8 Santin et al., Gynecol Oncol 2011; 122:495.

    9 Schilder et al., Gynecol Oncol 2005; 96:103

    10 Chung HC et al. J Clin Oncol 2019; 37:1470.

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  20. -Data Showcase Depth of Oncology Pipeline Using Seagen's Innovative Technologies-

    Seagen Inc. (NASDAQ:SGEN) today announced that preclinical data from its pipeline of novel targeted oncology drugs will be presented at the American Association for Cancer Research (AACR) Annual Meeting being held April 10-15, 2021. The oral and poster presentations will highlight several early-stage programs utilizing Seagen's leading antibody-drug conjugate (ADC) technology as well as its proprietary sugar-engineered antibody (SEA) technology.

    "Our research being presented at AACR describes intriguing preclinical data for three novel pipeline programs that are in ongoing clinical trials. This includes SEA-TGT, an anti-TIGIT antibody using our SEA technology…

    -Data Showcase Depth of Oncology Pipeline Using Seagen's Innovative Technologies-

    Seagen Inc. (NASDAQ:SGEN) today announced that preclinical data from its pipeline of novel targeted oncology drugs will be presented at the American Association for Cancer Research (AACR) Annual Meeting being held April 10-15, 2021. The oral and poster presentations will highlight several early-stage programs utilizing Seagen's leading antibody-drug conjugate (ADC) technology as well as its proprietary sugar-engineered antibody (SEA) technology.

    "Our research being presented at AACR describes intriguing preclinical data for three novel pipeline programs that are in ongoing clinical trials. This includes SEA-TGT, an anti-TIGIT antibody using our SEA technology, and two vedotin-based ADCs, SGN-B6A and SGN-STNV. We believe these three programs represent potential best-in-class or first-in-class targeted therapies for cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Among the findings, we will show the enhanced therapeutic effect in combining SEA-TGT with a checkpoint inhibitor or a vedotin-based ADC across different tumor models. In addition, we will report for the first time our preclinical data with SGN-STNV, a novel ADC targeting a carbohydrate antigen that may have broad applicability across solid tumors."

    Highlights of Seagen Programs Presented at AACR

    SEA-TGT

    Preclinical data will be presented for SEA-TGT, a novel investigational nonfucosylated human IgG1 TIGIT antibody, which utilizes Seagen's proprietary SEA technology that enhances functionality by targeting key immune activating Fc receptors. TIGIT is an inhibitory immune checkpoint that has emerged as a clinically relevant immuno-oncology target. The monotherapy and combinatorial activity of SEA-TGT was assessed and compared to TIGIT monoclonal antibodies (mAbs) with inert, standard, or effector function modified backbones in vivo and in vitro. Key preclinical findings were as follows:

    • the SEA-TGT backbone was distinct as it increased binding to activating FcγRIIIa with minimal binding to inhibitory FcγRIIb;
    • the empowered backbone had superior therapeutic properties including enhanced depletion of TIGIT-positive regulatory T-cells and activation of antigen-presenting cells both of which are important in promoting antitumor activity;
    • SEA-TGT demonstrated enhanced antitumor activity both as a single agent and in combination with anti-PD1 therapy; and,
    • SEA-TGT produced an enhanced therapeutic effect when combined with an immunogenic tumor cell death-inducing vedotin ADC.

    A phase 1 trial evaluating SEA-TGT alone and in combination with anti-PD-1 therapy in patients with advanced solid tumors and select lymphomas is ongoing.

    SGN-B6A

    Preclinical data will also be presented on SGN-B6A, an investigational ADC targeting integrin beta-6, which is overexpressed in numerous solid tumors and has been demonstrated to be a negative prognostic indicator across a diverse range of cancers, including non-small cell lung cancer (NSCLC). Data demonstrate SGN-B6A is active when dosed weekly in patient-derived xenograft models of NSCLC, representing both squamous and adenocarcinoma histology. A phase 1 trial evaluating monotherapy SGN-B6A in advanced solid tumors is ongoing.

    SGN-STNV

    SGN-STVN is an investigational ADC with a unique mechanism for targeting a carbohydrate antigen called Sialyl-Thomsen nouveau (STn), which is highly expressed on a variety of solid tumors including non-small cell lung, ovarian and gastric cancers. The preclinical data demonstrate SGN-STNV is highly specific for STn independent of protein identity, which could allow for the targeting of a range of tumor types that express different glycoproteins. In xenograft studies across key tumor types, the specificity and ability to target STn on multiple tumor-associated proteins led to durable tumor regressions. SGN-STNV was well-tolerated in in vivo studies and is being evaluated in an ongoing phase 1 study.

    Additional Details of Seagen Presentations at AACR Annual Meeting 2021

    All poster presentations will be available via on-demand view starting on April 10 at 8:30 a.m. Eastern Time. Oral symposium presentations will be available at the beginning of the session where the study is presented.

    Abstract Title

    Abstract #

    Date

    Presenter

    Oral

    Targeting Sialyl-Thomsen nouveau (STn) antigen with the SGN-STNV antibody-drug conjugate is effective in preclinical studies

    #50

    April 10 in session at 4:00 – 6:00 p.m. ET

    A. Schwartz

    E-Poster

    SEA-TGT is an empowered anti-TIGIT antibody that displays superior combinatorial activity with several therapeutic agents

    #1583

    April 10

    A. Smith

    Activity of SGN-B6A in patient-derived xenograft models of non-small cell lung cancer

    #914

    April 10

    R. Lyon

    Pharmacokinetics of tucatinib in healthy and hepatically-impaired volunteers

    #1371

    April 10

    A. Topletz-Erickson

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Forward-Looking Statements

    Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the potential of the Company's SEA-TGT, SGN-B6A and SGN-STNV product candidates, the enhanced therapeutic effect in combining SEA-TGT with a checkpoint inhibitor or a vedotin-based ADC and the potential of the Company's pipeline. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include without limitation the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the inability to show sufficient efficacy in clinical trials and the possibility of adverse regulatory actions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the Company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

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  21. Seagen Inc. (NASDAQ:SGEN) today announced that it will report its first quarter 2021 financial results on Thursday, April 29, 2021 after the close of U.S. financial markets. Following the announcement, Company management will host a conference call and webcast discussion of the results and provide a business update. Access to the event can be obtained as follows:

    Thursday, April 29, 2021
    1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time

    • Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10153242
    • Webcast with slides available at www.seagen.com in the Investors section. A webcast replay will be archived on the Company's website.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and…

    Seagen Inc. (NASDAQ:SGEN) today announced that it will report its first quarter 2021 financial results on Thursday, April 29, 2021 after the close of U.S. financial markets. Following the announcement, Company management will host a conference call and webcast discussion of the results and provide a business update. Access to the event can be obtained as follows:

    Thursday, April 29, 2021

    1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time

    • Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10153242
    • Webcast with slides available at www.seagen.com in the Investors section. A webcast replay will be archived on the Company's website.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    View Full Article Hide Full Article
  22. - Enfortumab vedotin to be reviewed under accelerated assessment for the treatment of locally advanced or metastatic urothelial cancer -

    Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced that a marketing authorization application (MAA) for enfortumab vedotin was accepted by the European Medicines Agency (EMA). The MAA requests review of enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic…

    - Enfortumab vedotin to be reviewed under accelerated assessment for the treatment of locally advanced or metastatic urothelial cancer -

    Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced that a marketing authorization application (MAA) for enfortumab vedotin was accepted by the European Medicines Agency (EMA). The MAA requests review of enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. If approved, enfortumab vedotin would be the first antibody-drug conjugate (ADC) available in the European Union for people living with urothelial cancer.

    Enfortumab vedotin will be reviewed under accelerated assessment, which means the EMA's Committee for Medicinal Products for Human Use (CHMP) can reduce the timeframe for evaluation.

    The MAA is based on the global phase 3 EV-301 trial, which evaluated enfortumab vedotin versus chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. Results from the trial, which had a primary endpoint of overall survival for patients treated with PADCEV versus chemotherapy, were published in the New England Journal of Medicine.

    "In the European Union, it is estimated that 118,000 people are diagnosed with urothelial cancer each year, and 52,000 die as a result of the disease," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "People with advanced urothelial cancer face an urgent need for new treatment options, which is reflected in the CHMP's decision to grant accelerated assessment. We will continue to work with the CHMP toward our goal of securing marketing authorization as soon as possible."

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.2 In Europe, it is estimated that 118,000 patients are diagnosed with this form of cancer and 52,000 deaths are reported annually.3

    Locally advanced and metastatic urothelial cancer is an aggressive disease that is associated with poor survival and high healthcare costs.4 Five-year relative survival rates for metastatic disease are estimated to be approximately 7 percent.5

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.6

    About Enfortumab Vedotin

    Enfortumab vedotin is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.7,8 Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).8

    PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information

    Warnings and Precautions

    Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

    Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement.

    Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

    Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

    Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

    Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

    Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

    Drug Interactions

    Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About the Astellas and Seagen Collaboration

    Astellas and Seagen Inc. are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of enfortumab vedotin, including its efficacy, safety and therapeutic uses; and the potential to obtain regulatory approval of enfortumab vedotin in the European Union. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that enfortumab vedotin may not ultimately be approved in the European Union for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting, in a timely manner or at all; and that setbacks in the development and commercialization of enfortumab vedotin could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, failure to establish sufficient efficacy in clinical trials, adverse regulatory actions or other factors. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    _______________________________

    1 American Society of Clinical Oncology. Bladder cancer: introduction. Published October 2017. https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed March 4, 2021.

    2 Cancer today: data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/home. Accessed March 4, 2021.

    3 Wong MC, Fung FD, Leung C, et al. Scientific Reports. 2018;8(1):1129.

    4 Shah MV, McGovern A, Hepp Z. Targeted Literature Review of the Burden of Illness in UC (PCN108). Value Health. 2018;21(3):S32-S33.

    5 von der Maase H, Sengelov L, Roberts J, Ricci S, et al. Long term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602 8.

    6 Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021; 10.1056/NEJMoa2035807.

    7 PADCEV [package insert]. Northbrook, IL: Astellas Pharma Inc.

    8 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

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  23. TOKYO and BOTHELL, Wash., March 26, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced that a marketing authorization application (MAA) for enfortumab vedotin was accepted by the European Medicines Agency (EMA). The MAA requests review of enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. If approved, enfortumab vedotin would be the first antibody-drug conjugate…

    TOKYO and BOTHELL, Wash., March 26, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced that a marketing authorization application (MAA) for enfortumab vedotin was accepted by the European Medicines Agency (EMA). The MAA requests review of enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. If approved, enfortumab vedotin would be the first antibody-drug conjugate (ADC) available in the European Union for people living with urothelial cancer.

    Enfortumab vedotin will be reviewed under accelerated assessment, which means the EMA's Committee for Medicinal Products for Human Use (CHMP) can reduce the timeframe for evaluation.

    The MAA is based on the global phase 3 EV-301 trial, which evaluated enfortumab vedotin versus chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. Results from the trial, which had a primary endpoint of overall survival for patients treated with PADCEV versus chemotherapy, were published in the New England Journal of Medicine.

    "In the European Union, it is estimated that 118,000 people are diagnosed with urothelial cancer each year, and 52,000 die as a result of the disease," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "People with advanced urothelial cancer face an urgent need for new treatment options, which is reflected in the CHMP's decision to grant accelerated assessment. We will continue to work with the CHMP toward our goal of securing marketing authorization as soon as possible."

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.2 In Europe, it is estimated that 118,000 patients are diagnosed with this form of cancer and 52,000 deaths are reported annually.3

    Locally advanced and metastatic urothelial cancer is an aggressive disease that is associated with poor survival and high healthcare costs.4 Five-year relative survival rates for metastatic disease are estimated to be approximately 7 percent.5

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.6 

    About Enfortumab Vedotin

    Enfortumab vedotin is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.7,8 Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).8

    PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information 

    Warnings and Precautions 

    Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV.  SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. 

    Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement.  

    Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions. 

    Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C.  In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV. 

    Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy. 

    Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders. 

    Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions. 

    Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose. 

    Adverse Reactions 

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%). 

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%). 

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%). 

    Lab Abnormalities 

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).  

    Drug Interactions 

    Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations 

    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose. 

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment. 

    For more information, please see the full Prescribing Information for PADCEV here. 

    About the Astellas and Seagen Collaboration

    Astellas and Seagen Inc. are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of enfortumab vedotin, including its efficacy, safety and therapeutic uses; and the potential to obtain regulatory approval of enfortumab vedotin in the European Union. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that enfortumab vedotin may not ultimately be approved in the European Union for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting, in a timely manner or at all; and that setbacks in the development and commercialization of enfortumab vedotin could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, failure to establish sufficient efficacy in clinical trials, adverse regulatory actions or other factors. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    1 American Society of Clinical Oncology. Bladder cancer: introduction. Published October 2017. https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed March 4, 2021.

    2 Cancer today: data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/home. Accessed March 4, 2021.

    3 Wong MC, Fung FD, Leung C, et al. Scientific Reports. 2018;8(1):1129.

    4 Shah MV, McGovern A, Hepp Z. Targeted Literature Review of the Burden of Illness in UC (PCN108). Value Health. 2018;21(3):S32-S33.

    5 von der Maase H, Sengelov L, Roberts J, Ricci S, et al. Long term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602 8.

    6 Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021; 10.1056/NEJMoa2035807.

    7 PADCEV [package insert]. Northbrook, IL: Astellas Pharma Inc.

    8 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/european-medicines-agency-accepts-marketing-authorization-application-for-enfortumab-vedotin-301256415.html

    SOURCE Astellas Pharma Inc.

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  24. Seagen Inc. (NASDAQ:SGEN) today announced that it has been notified of an unsolicited "mini-tender" offer dated February 22, 2021, made by TRC Capital Investment Corporation, an Ontario, Canada corporation, to purchase up to 1,000,000 shares of Seagen's common stock. According to TRC, its "mini-tender" offer price of $151.00 per share was approximately 4.28% below the closing price of Seagen's common stock on February 19, 2021, the last trading day prior to the date of its offer.

    Seagen does not endorse TRC Capital's unsolicited "mini-tender" offer and is not associated in any way with TRC Capital, its "mini-tender" offer, or its "mini-tender" offer documents. Seagen recommends that Seagen shareholders reject the offer and not tender their…

    Seagen Inc. (NASDAQ:SGEN) today announced that it has been notified of an unsolicited "mini-tender" offer dated February 22, 2021, made by TRC Capital Investment Corporation, an Ontario, Canada corporation, to purchase up to 1,000,000 shares of Seagen's common stock. According to TRC, its "mini-tender" offer price of $151.00 per share was approximately 4.28% below the closing price of Seagen's common stock on February 19, 2021, the last trading day prior to the date of its offer.

    Seagen does not endorse TRC Capital's unsolicited "mini-tender" offer and is not associated in any way with TRC Capital, its "mini-tender" offer, or its "mini-tender" offer documents. Seagen recommends that Seagen shareholders reject the offer and not tender their shares in response to this unsolicited offer, for the reasons described below.

    TRC has made many similar "mini-tender" offers for the shares of other companies. "Mini-tender" offers are designed to seek less than five percent of a company's outstanding shares, thereby avoiding many disclosure and procedural requirements of the U.S. Securities and Exchange Commission (SEC) because they are below the SEC's threshold to provide such disclosure and procedural protections for investors.

    The SEC has cautioned investors about "mini-tender" offers in an investor alert. The SEC noted that these offers "have been increasingly used to catch investors off guard" and that many investors who hear about "mini-tender" offers "surrender their securities without investigating the offer, assuming that the price offered includes the premium usually present in larger, traditional tender offers."

    To read more about the risks of "mini-tender" offers, please review the alert on the SEC's website at http://www.sec.gov/investor/pubs/minitend.htm.

    TRC's "mini-tender" offer is subject to numerous conditions, including TRC obtaining sufficient financing available to consummate the offer on terms satisfactory to TRC in its reasonable discretion. Seagen urges shareholders to obtain current stock quotes for their shares of Seagen common stock, review the terms and conditions to the offer, consult with their broker or financial adviser and exercise caution with respect to TRC Capital's "mini-tender" offer. Shareholders who have already tendered shares should consider the advisability of withdrawing their shares as permitted under TRC's Offer to Purchase documents.

    According to the offer documents, the offer is currently scheduled to expire at 12:01 a.m., Eastern time, on March 23, 2021.

    Seagen requests that a copy of this news release be included with all distributions of materials relating to TRC's "mini-tender" offer related to shares of Seagen's common stock.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    Forward-Looking Statements

    Certain statements made in this press release are forward-looking and based upon the current beliefs and expectations of Seagen's management. These statements are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Factors that may cause such a difference include without limitation: the risks that Seagen's ADCETRIS, PADCEV and TUKYSA net sales, revenues, expenses, costs, and other financial guidance may not be as expected; risks and uncertainties associated with maintaining or increasing sales of ADCETRIS, PADCEV and TUKYSA due to competition, unexpected adverse events, regulatory action, government pricing and/or reimbursement actions, market adoption by physicians, impacts associated with COVID-19 or other factors; the risks that Seagen or its collaborators may be delayed or unsuccessful in planned clinical trial initiations, enrollment in and conduct of clinical trials, obtaining data from clinical trials, planned regulatory submissions, and regulatory approvals in the U.S. and in other countries in each case for a variety of reasons including the difficulty and uncertainty of pharmaceutical product development, negative or disappointing clinical trial results, unexpected adverse events or regulatory actions and the inherent uncertainty associated with the regulatory approval process; and risks related to the duration and severity of the COVID-19 pandemic and resulting global economic, financial and healthcare system disruptions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the SEC. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

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  25. Seagen Inc. (NASDAQ:SGEN) today announced that management will participate in a fireside chat at the Cowen 41st Annual Healthcare Conference on Monday, March 1, 2021 at 2:40 p.m. Eastern Time. The presentation will be webcast live and available for replay from Seagen's website at www.seagen.com in the Investors section.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow…

    Seagen Inc. (NASDAQ:SGEN) today announced that management will participate in a fireside chat at the Cowen 41st Annual Healthcare Conference on Monday, March 1, 2021 at 2:40 p.m. Eastern Time. The presentation will be webcast live and available for replay from Seagen's website at www.seagen.com in the Investors section.

    About Seagen

    Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company's marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

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  26. - Submissions will be Reviewed Under Real-Time Oncology Review Based on Clinical Trials EV-301 and Cohort 2 of EV-201 -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced completion of submissions for two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for PADCEV® (enfortumab vedotin-ejfv). One submission, based on the phase 3 EV-301 trial, seeks to convert PADCEV's accelerated approval to regular approval. The second submission, based on the pivotal trial EV-201's second cohort, requests an expansion of the current label to include patients with locally advanced or metastatic urothelial cancer who have been…

    - Submissions will be Reviewed Under Real-Time Oncology Review Based on Clinical Trials EV-301 and Cohort 2 of EV-201 -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced completion of submissions for two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for PADCEV® (enfortumab vedotin-ejfv). One submission, based on the phase 3 EV-301 trial, seeks to convert PADCEV's accelerated approval to regular approval. The second submission, based on the pivotal trial EV-201's second cohort, requests an expansion of the current label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin.

    The FDA is reviewing both applications under the Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.

    "The FDA's review of our applications under Real-Time Oncology Review supports our efforts to expand PADCEV's availability as a treatment option for more patients as quickly as possible," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "Locally advanced or metastatic urothelial cancer is an aggressive disease with limited treatment options."

    The sBLA for regular approval of PADCEV in the U.S. is supported by data from the global EV-301 phase 3 confirmatory trial, which compared PADCEV to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The trial's primary endpoint was overall survival of patients treated with PADCEV vs. chemotherapy, and full results were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and published in the New England Journal of Medicine.1

    The second submission, for a label expansion in the U.S., is based on results from the second cohort of EV-201, a pivotal phase 2 clinical trial evaluating PADCEV in patients with locally advanced or metastatic urothelial cancer who had received prior immunotherapy treatment but were not eligible for cisplatin. The trial's primary endpoint was objective response rate, and full results were presented at ASCO GU.2

    "Advanced bladder cancer patients urgently need more treatment options," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "Based on recently presented clinical trial results, PADCEV could address a significant unmet need for more patients with advanced urothelial cancer after initial immunotherapy treatment."

    In 2019 PADCEV received accelerated approval in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery in a locally advanced or metastatic urothelial cancer setting. PADCEV is currently only approved for use in the U.S.

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally. The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.3 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.4

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.5

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5,6 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).5 PADCEV is co-developed by Seagen and Astellas.

    PADCEV Important Safety Information

    Warnings and Precautions

    • Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis (DKA), in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.
    • Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.
    • Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.
    • Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. Monitor patients for skin reactions. Consider appropriate treatment, such as topical corticosteroids and antihistamines for skin reactions, as clinically indicated. For severe (Grade 3) skin reactions, withhold PADCEV until improvement or resolution and administer appropriate medical treatment. Permanently discontinue PADCEV in patients that develop Grade 4 or recurrent Grade 3 skin reactions.
    • Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
    • Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

    Drug Interactions

    • Effects of other drugson PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    • Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.
    • Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About the Seagen and Astellas Collaboration

    Seagen and Astellas are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the potential conversion of PADCEV's current accelerated approval in the U.S. to regular approval and the potential expansion of the current PADCEV label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin, and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that the sBLA submissions based on the EV-301 and EV-201 second cohort clinical trials may not be accepted for filing by, or ultimately approved by, the FDA in a timely manner or at all; that the results of the EV-301 clinical trial may not be sufficient to convert PADCEV's accelerated approval in the U.S. to regular approval and that the results of the second cohort of the EV-201 clinical trial may not be sufficient to support the requested label expansion; that, even if PADCEV receives regular approval and even if the PADCEV label is expanded based on the results of the second cohort of the EV-201 clinical trial, the product labeling may not be as broad or desirable as requested or anticipated; and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the failure of ongoing and subsequent clinical trials to establish sufficient efficacy, or as a result of adverse regulatory actions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    References

    _________________________________

    1

    Powles T, Rosenberg J, Sonpavde G, et al. Primary Results of EV-301: A Phase 3 Trial of Enfortumab Vedotin vs Chemotherapy in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma. ASCO Meeting Library 2021. https://meetinglibrary.asco.org/record/194738/abstract. Accessed February 11, 2021

    2

    Balar AV, McGregor B, Rosenberg J, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. ASCO Meeting Library 2021. https://meetinglibrary.asco.org/record/194731/abstract. Accessed February 11, 2021.

    3

    American Society of Clinical Oncology. Bladder cancer: introduction (5-2019). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed January 27, 2021.

    4

    Cancer today: data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/home. Accessed January 27, 2021.

    5

    PADCEV [package insert] Northbrook, IL: Astellas Pharma Inc.

    6

    Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

     

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  27. TOKYO and BOTHELL, Wash., Feb. 18, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced completion of submissions for two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for PADCEV® (enfortumab vedotin-ejfv). One submission, based on the phase 3 EV-301 trial, seeks to convert PADCEV's accelerated approval to regular approval. The second submission, based on the pivotal trial EV-201's second cohort, requests an expansion of the current label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for…

    TOKYO and BOTHELL, Wash., Feb. 18, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced completion of submissions for two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for PADCEV® (enfortumab vedotin-ejfv). One submission, based on the phase 3 EV-301 trial, seeks to convert PADCEV's accelerated approval to regular approval. The second submission, based on the pivotal trial EV-201's second cohort, requests an expansion of the current label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin.

    The FDA is reviewing both applications under the Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. 

    "The FDA's review of our applications under Real-Time Oncology Review supports our efforts to expand PADCEV's availability as a treatment option for more patients as quickly as possible," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "Locally advanced or metastatic urothelial cancer is an aggressive disease with limited treatment options."

    The sBLA for regular approval of PADCEV in the U.S. is supported by data from the global EV-301 phase 3 confirmatory trial, which compared PADCEV to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The trial's primary endpoint was overall survival of patients treated with PADCEV vs. chemotherapy, and full results were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and published in the New England Journal of Medicine.[1]

    The second submission, for a label expansion in the U.S., is based on results from the second cohort of EV-201, a pivotal phase 2 clinical trial evaluating PADCEV in patients with locally advanced or metastatic urothelial cancer who had received prior immunotherapy treatment but were not eligible for cisplatin. The trial's primary endpoint was objective response rate, and full results were presented at ASCO GU.[2]

    "Advanced bladder cancer patients urgently need more treatment options," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "Based on recently presented clinical trial results, PADCEV could address a significant unmet need for more patients with advanced urothelial cancer after initial immunotherapy treatment."

    In 2019 PADCEV received accelerated approval in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery in a locally advanced or metastatic urothelial cancer setting. PADCEV is currently only approved for use in the U.S.

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally. The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.[3] Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.[4]

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.[5]

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5,[6] Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).5 PADCEV is co-developed by Astellas and Seagen.

    PADCEV Important Safety Information

    Warnings and Precautions

    • Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis (DKA), in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.
    • Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.
    • Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.
    • Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. Monitor patients for skin reactions. Consider appropriate treatment, such as topical corticosteroids and antihistamines for skin reactions, as clinically indicated. For severe (Grade 3) skin reactions, withhold PADCEV until improvement or resolution and administer appropriate medical treatment. Permanently discontinue PADCEV in patients that develop Grade 4 or recurrent Grade 3 skin reactions.
    • Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
    • Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

    Drug Interactions

    • Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    • Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.
    • Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About the Astellas and Seagen Collaboration

    Astellas and Seagen are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the potential conversion of PADCEV's current accelerated approval in the U.S. to regular approval and the potential expansion of the current PADCEV label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin, and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that the sBLA submissions based on the EV-301 and EV-201 second cohort clinical trials may not be accepted for filing by, or ultimately approved by, the FDA in a timely manner or at all; that the results of the EV-301 clinical trial may not be sufficient to convert PADCEV's accelerated approval in the U.S. to regular approval and that the results of the second cohort of the EV-201 clinical trial may not be sufficient to support the requested label expansion; that, even if PADCEV receives regular approval and even if the PADCEV label is expanded based on the results of the second cohort of the EV-201 clinical trial, the product labeling may not be as broad or desirable as requested or anticipated; and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the failure of ongoing and subsequent clinical trials to establish sufficient efficacy, or as a result of adverse regulatory actions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    [1] Powles T, Rosenberg J, Sonpavde G, et al. Primary Results of EV-301: A Phase 3 Trial of Enfortumab Vedotin vs Chemotherapy in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma. ASCO Meeting Library 2021. https://meetinglibrary.asco.org/record/194738/abstract.  Accessed February 11, 2021.

    [2] Balar AV, McGregor B, Rosenberg J, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. ASCO Meeting Library 2021. https://meetinglibrary.asco.org/record/194731/abstract. Accessed February 11, 2021.

    [3] American Society of Clinical Oncology. Bladder cancer: introduction (5-2019). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed January 27, 2021.

    [4] Cancer today: data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/home. Accessed January 27, 2021.

    [5] PADCEV [package insert] Northbrook, IL: Astellas Pharma Inc.

    [6] Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/astellas-and-seagen-announce-submission-of-two-supplemental-biologics-license-applications-to-the-us-fda-for-padcev-enfortumab-vedotin-ejfv-in-locally-advanced-or-metastatic-urothelial-cancer-301230509.html

    SOURCE Astellas Pharma Inc.

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  28. - Durable Tumor Responses Experienced Among Patients Previously Treated with Immunotherapy in Second Cohort of EV-201 Trial -

    - Data Presented in Oral Presentation at the 2021 ASCO Genitourinary Cancers Symposium -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced results from the second cohort (cohort 2) of patients in the pivotal phase 2 single-arm EV-201 trial. In the trial, 52 percent of patients who received PADCEV® (enfortumab vedotin-ejfv) had an objective response (95 percent Confidence Interval [CI]: 40.8, 62.4) and the median duration of response was 10.9 months (95 percent CI: 5.8, NR). Twenty percent of patients had a complete response, the absence…

    - Durable Tumor Responses Experienced Among Patients Previously Treated with Immunotherapy in Second Cohort of EV-201 Trial -

    - Data Presented in Oral Presentation at the 2021 ASCO Genitourinary Cancers Symposium -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced results from the second cohort (cohort 2) of patients in the pivotal phase 2 single-arm EV-201 trial. In the trial, 52 percent of patients who received PADCEV® (enfortumab vedotin-ejfv) had an objective response (95 percent Confidence Interval [CI]: 40.8, 62.4) and the median duration of response was 10.9 months (95 percent CI: 5.8, NR). Twenty percent of patients had a complete response, the absence of detectable cancer, after PADCEV treatment, and 31 percent had a partial response. Adverse events were consistent with those observed in previous trial data, with the most common all-grade treatment-related adverse events (AEs) being alopecia (51 percent), peripheral sensory neuropathy (47 percent), and fatigue (34 percent).

    Cohort 2 of the EV-201 trial evaluated PADCEV in patients with locally advanced or metastatic urothelial cancer who had been previously treated with a PD-1/L1 inhibitor, had not received a platinum-containing chemotherapy in this setting, and were ineligible for cisplatin. Urothelial cancer is the most common type of bladder cancer and can also be found in the renal pelvis, ureter and urethra.1

    The findings were presented today in an oral presentation as part of the virtual scientific program of the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) (Abstract 394).

    "Roughly half of all patients with locally advanced or metastatic urothelial cancer have comorbidities that make them ineligible for cisplatin-based chemotherapy, and after progression on first-line immunotherapy, there are few effective treatment options," said Arjun Balar, M.D., Associate Professor of Medicine, Director Genitourinary Medical Oncology Program, NYU Laura and Isaac Perlmutter Cancer Center, NYU Langone Health and an investigator for the trial. "Results from EV-201 cohort 2 indicate that enfortumab vedotin may be an important therapeutic option for these patients."

    "We're pleased that PADCEV provided meaningful clinical benefit to a group of patients who historically have very few options and may choose not to pursue further treatment for the disease," said Roger Dansey, M.D., Chief Medical Officer, Seagen.

    "Fifty-two percent of patients in this study cohort responded to PADCEV – including some patients who showed no detectable cancer following treatment – an important result for people with this difficult-to-treat form of urothelial cancer," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas.

    The results are expected to be submitted to the U.S. Food and Drug Administration by the end of March as part of a supplemental biologics licensing application. EV-201 results will also be included in submissions to some global health authorities.

    EV-201 Cohort 2 Trial Results

    In cohort 2 of the dual-cohort trial, 52 percent of patients who received PADCEV had an objective response (46/89); (95 percent CI: 40.8, 62.4) per blinded independent central review (the primary endpoint), with 20 percent of patients (18/89) experiencing a complete response and 31 percent of patients experiencing a partial response (28/89).

    In the trial's secondary endpoints, duration of response lasted a median of 10.9 months (95 percent CI: 5.8, NR). Patients lived a median of 5.8 months without cancer progression (progression-free survival) (95 percent CI: 5.0, 8.3), and had a median overall survival of 14.7 months (95 percent CI: 10.5,18.2).

    Grade 3 or greater treatment-related AEs of interest included skin reactions (17 percent), peripheral neuropathy (8 percent) and hyperglycemia (6 percent). Four deaths were reported as treatment-related by investigators in patients age 75 years and older with multiple comorbidities.

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.2

    About the EV-201 Trial

    The EV-201 trial (NCT03219333) is a single-arm, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.

    The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.3

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.3,4 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).4 PADCEV is co-developed by Seagen and Astellas.

    PADCEV Important Safety Information

    Warnings and Precautions

    • Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis (DKA), in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.
    • Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.
    • Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.
    • Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. Monitor patients for skin reactions. Consider appropriate treatment, such as topical corticosteroids and antihistamines for skin reactions, as clinically indicated. For severe (Grade 3) skin reactions, withhold PADCEV until improvement or resolution and administer appropriate medical treatment. Permanently discontinue PADCEV in patients that develop Grade 4 or recurrent Grade 3 skin reactions.
    • Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
    • Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

    Drug Interactions

    • Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    • Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.
    • Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Seagen

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About Astellas

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About the Seagen and Astellas Collaboration

    Seagen and Astellas are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the submission of data from cohort 2 of the EV-201 trial for presentation at an upcoming scientific congress; intended regulatory actions, including plans to submit a supplemental biologics licensing application to the FDA and to make submissions to global health authorities; and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibilities that we may experience delays in the submission of results to the FDA; that the results from cohort 2 of the EV-201 trial may not be support any approvals by regulatory authorities; that, even if PADCEV receives an additional approval in the U.S. or an approval in any global registrations, the product labeling may not be as broad or desirable as anticipated; that ongoing and subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    References

    ________________

    1

    American Society of Clinical Oncology. Bladder cancer: introduction (5-2019). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed January 27, 2021.

    2

    Cancer today: data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/home. Accessed January 27, 2021.

    3

    PADCEV [package insert] Northbrook, IL: Astellas, Inc.

    4

    Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

     

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  29. TOKYO and BOTHELL, Wash., Feb. 12, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced primary results from the phase 3 EV-301 trial comparing PADCEV® (enfortumab vedotin-ejfv) to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. At the time of pre-specified interim analysis, patients who received PADCEV in the trial lived a median of 3.9 months longer than those who received chemotherapy. Median overall survival was 12.9 vs. 9.0 months, respectively (HR=0.70 [95 percent Confidence Interval (CI): 0.56-0.89], p=0.001). For…

    TOKYO and BOTHELL, Wash., Feb. 12, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced primary results from the phase 3 EV-301 trial comparing PADCEV® (enfortumab vedotin-ejfv) to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. At the time of pre-specified interim analysis, patients who received PADCEV in the trial lived a median of 3.9 months longer than those who received chemotherapy. Median overall survival was 12.9 vs. 9.0 months, respectively (HR=0.70 [95 percent Confidence Interval (CI): 0.56-0.89], p=0.001). For patients in the PADCEV arm of the trial, maculopapular rash, fatigue and decreased neutrophil count were the most frequent Grade 3 or greater treatment-related adverse events (TRAEs) occurring in more than 5 percent of patients.

    Urothelial cancer is the most common type of bladder cancer and can also be found in the renal pelvis, ureter and urethra.1

    The findings were published in the New England Journal of Medicine and presented during the virtual scientific program of the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) (Abstract 393).

    "Improving survival is especially meaningful in patients who have had their cancer progress following chemotherapy or other treatment," said Daniel P. Petrylak, M.D., Professor of Medicine and of Urology, Yale Cancer Center, and corresponding author of the published study.

    "Enfortumab vedotin is the first medicine to reduce the risk of death compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who have received a platinum-containing chemotherapy and an immunotherapy," said Professor Thomas Powles, M.D., Director, Barts Cancer Centre, Queen Mary University of London, who presented results at ASCO GU.

    Patients who received PADCEV in the trial also showed improvement in the following secondary endpoints:

    • Median progression-free survival, which is the time without progression of cancer, was 5.6 months for PADCEV vs. 3.7 months for chemotherapy (HR=0.62 [95 percent CI: 0.51-0.75]; p<0.00001).
    • Overall response rate, the percentage of patients with either complete or partial response, was 40.6 percent vs. 17.9 percent of patients in the chemotherapy arm (p<0.001).
    • Disease control rate (DCR), which is the percentage of patients who have achieved complete response, partial response or had stable disease, was 71.9 percent for PADCEV and 53.4 percent for chemotherapy (p<0.001).

    Other safety findings included:

    • Rates of serious TRAEs were comparable between treatment arms (23 percent of patients receiving PADCEV vs. 23 percent receiving chemotherapy).
    • Grade 3 or greater TRAEs were experienced by approximately 50 percent of patients in both study arms. Grade 3 or greater TRAEs occurring in more than 5 percent of patients receiving PADCEV were maculopapular rash (occurring in 7 percent of patients receiving PADCEV vs. 0 percent of patients receiving chemotherapy), fatigue (6 percent vs. 4.5 percent) and decreased neutrophil count (6 percent vs. 13 percent).

    "Patients who received PADCEV lived longer than those who received chemotherapy – an important finding, especially in light of the high unmet need faced by people with advanced urothelial cancer," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas.

    "Since its accelerated approval by the FDA in late 2019, physicians have adopted PADCEV into their practice, and these confirmatory results provide additional evidence of its benefit for people living with advanced bladder cancer," said Roger Dansey, M.D., Chief Medical Officer, Seagen.

    Results of EV-301 are expected to be submitted to the U.S. Food and Drug Administration by the end of March as the confirmatory trial following the drug's accelerated approval in 2019. The results of EV-301 will also be included in submissions to global health authorities.

    About Urothelial Cancer

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.2

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

    About PADCEV® (enfortumab vedotin-ejfv)

    PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.3

    PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.3,4 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).4 PADCEV is co-developed by Astellas and Seagen.

    PADCEV Important Safety Information

    Warnings and Precautions

    • Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis (DKA), in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.
    • Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.
    • Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.
    • Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement. Monitor patients for skin reactions. Consider appropriate treatment, such as topical corticosteroids and antihistamines for skin reactions, as clinically indicated. For severe (Grade 3) skin reactions, withhold PADCEV until improvement or resolution and administer appropriate medical treatment. Permanently discontinue PADCEV in patients that develop Grade 4 or recurrent Grade 3 skin reactions.
    • Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
    • Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    Adverse Reactions

    Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

    Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

    The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

    Lab Abnormalities

    In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

    Drug Interactions

    • Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

    Specific Populations

    • Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.
    • Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the full Prescribing Information for PADCEV here.

    About Astellas 

    Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

    About Seagen 

    Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

    About the Astellas and Seagen Collaboration

    Astellas and Seagen are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009.

    Astellas Cautionary Notes

    In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

    Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

    Seagen Forward Looking Statements

    Certain statements made in this press release are forward looking, such as those, among others, relating to the submission of data from the EV-301 trial for presentation at an upcoming scientific congress; intended regulatory actions, including plans to submit the results of the EV-301 trial to the FDA as the confirmatory trial following the drug's accelerated approval in the U.S. and plans to seek global registrations; and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibilities that we may experience delays in the submission of results to the FDA; that the results from the EV-301 trial may not be sufficient to convert PADCEV's accelerated approval in the U.S. to regular approval or to support any other global registrations; that, even if PADCEV receives regular approval in the U.S. or any other global registrations, the product labeling may not be as broad or desirable as anticipated; that ongoing and subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; and that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

    References

    1 American Society of Clinical Oncology. Bladder cancer: introduction (5-2019). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed January 27, 2021.

    2 Cancer today: data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/home. Accessed January 27, 2021.

    3 PADCEV [package insert] Northbrook, IL: Astellas Pharma Inc.

    4 Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 2016;76(10):3003-13.

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    SOURCE Astellas Pharma Inc.

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  30. TOKYO and BOTHELL, Wash., Feb. 12, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced results from the second cohort (cohort 2) of patients in the pivotal phase 2 single-arm EV-201 trial. In the trial, 52 percent of patients who received PADCEV® (enfortumab vedotin-ejfv) had an objective response (95 percent Confidence Interval [CI]: 40.8, 62.4) and the median duration of response was 10.9 months (95 percent CI: 5.8, NR). Twenty percent of patients had a complete response, the absence of detectable cancer, after PADCEV treatment, and 31 percent had a partial response. Adverse events were consistent with those observed in previous trial data…

    TOKYO and BOTHELL, Wash., Feb. 12, 2021 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced results from the second cohort (cohort 2) of patients in the pivotal phase 2 single-arm EV-201 trial. In the trial, 52 percent of patients who received PADCEV® (enfortumab vedotin-ejfv) had an objective response (95 percent Confidence Interval [CI]: 40.8, 62.4) and the median duration of response was 10.9 months (95 percent CI: 5.8, NR). Twenty percent of patients had a complete response, the absence of detectable cancer, after PADCEV treatment, and 31 percent had a partial response. Adverse events were consistent with those observed in previous trial data, with the most common all-grade treatment-related adverse events (AEs) being alopecia (51 percent), peripheral sensory neuropathy (47 percent), and fatigue (34 percent).