1. 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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  2. - 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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  3. 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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  4. - 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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  5. 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.

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/astellas-and-seagen-announce-phase-3-trial-results-demonstrating-survival-advantage-of-padcev-enfortumab-vedotin-ejfv-in-patients-with-previously-treated-advanced-urothelial-cancer-301227720.html

    SOURCE Astellas Pharma Inc.

    View Full Article Hide Full Article
  6. 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).

    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."

    "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.

    "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.

    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 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 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.

    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.

     

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/astellas-and-seagen-announce-presentation-of-results-from-padcev-enfortumab-vedotin-ejfv-pivotal-trial-in-patients-with-previously-treated-advanced-urothelial-cancer-who-were-ineligible-for-cisplatin-chemotherapy-301227727.html

    SOURCE Astellas Pharma Inc.

    View Full Article Hide Full Article
  7. - Findings from the EV-301 Trial Showed Significant Improvements in Overall Survival and Progression-Free Survival Compared to Chemotherapy -

    - EV-301 Intended to Support Global Registrations, Convert Accelerated to Regular Approval in U.S. -

    - Data Published in the New England Journal of Medicine, Presented 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 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…

    - Findings from the EV-301 Trial Showed Significant Improvements in Overall Survival and Progression-Free Survival Compared to Chemotherapy -

    - EV-301 Intended to Support Global Registrations, Convert Accelerated to Regular Approval in U.S. -

    - Data Published in the New England Journal of Medicine, Presented 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 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).

    "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.

    "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.

    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 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 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.

    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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  8. - Approved for Adult Patients with HER2-Positive Metastatic Breast Cancer Who Have Received at Least Two Prior Anti-HER2 Treatment Regimens -

    - First HER-2 Tyrosine Kinase Inhibitor Combination Regimen to Improve Overall and Progression-Free Survival in Previously Treated Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases -

    Seagen Inc. (NASDAQ:SGEN) today announced that the European Commission (EC) has granted marketing authorization for TUKYSA® (tucatinib) 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 an oral, small molecule tyrosine…

    - Approved for Adult Patients with HER2-Positive Metastatic Breast Cancer Who Have Received at Least Two Prior Anti-HER2 Treatment Regimens -

    - First HER-2 Tyrosine Kinase Inhibitor Combination Regimen to Improve Overall and Progression-Free Survival in Previously Treated Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases -

    Seagen Inc. (NASDAQ:SGEN) today announced that the European Commission (EC) has granted marketing authorization for TUKYSA® (tucatinib) 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 an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.1,2

    "This approval is a significant advancement for patients in Europe, who will for the first time have an approved medicine demonstrating a survival benefit for HER2-positive metastatic breast cancer after disease progression following two standard anti-HER2 treatment regimens," said Prof. Dr. Med Volkmar Mueller, Deputy Director at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany and investigator for the pivotal trial. "In the HER2CLIMB pivotal trial, the tucatinib combination regimen improved overall and progression-free survival compared to trastuzumab and capecitabine alone, including in patients with active, untreated or progressing brain metastases, a population with significant unmet need."

    "The TUKYSA combination is a landmark therapy for patients with HER2-positive metastatic breast cancer with or without brain metastases, extending overall survival in these patients after two prior anti-HER2 treatment regimens," said Clay Siegall, Ph.D., Chief Executive Officer at Seagen. "We are pleased TUKYSA is now approved in Europe, and we look forward to further collaborating with individual countries to ensure it is available to patients."

    The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion for TUKYSA in December 2020. The approval of TUKYSA is valid in all countries of the European Union, as well as Norway, Liechtenstein, Iceland and Northern Ireland.

    HER2CLIMB Efficacy and Safety

    Patients who received TUKYSA in combination with trastuzumab and capecitabine in the pivotal trial had a 46 percent reduction in the risk of cancer progression or death (PFS), the primary endpoint, compared to patients who received trastuzumab and capecitabine alone (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001) and improved overall survival with a reduction in the risk of death by 34 percent (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048). The most common adverse reactions occurring in 20 percent or more of patients who received TUKYSA were diarrhea, nausea, vomiting, stomatitis, AST increase, ALT increase, and rash.1

    The pivotal trial, HER2CLIMB, is a randomized (2:1), double-blind, placebo-controlled, active comparator, global trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1 SmPC).

    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 2020, more than two million new cases of breast cancer were diagnosed worldwide, including 531,086 in Europe.3 Between 15 and 20 percent of breast cancer cases are HER2-positive.4 HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.4,5,6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.7,8,9

    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 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 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 September 30, 2020 and the company's Current Report on Form 8-K dated December 30, 2020 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

    Anita Kulukian, Patrice Lee, Janelle Taylor, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor ModelsMol Cancer Ther2020;19:976-987.

    3

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

    4

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

    5

    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.

    6

    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.

    7

    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.

    8

    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.

    9

    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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  9. -Net Product Sales of $1 Billion in 2020, an Increase of 59 Percent Over 2019-

    -European Medicines Agency's CHMP Adopted Positive Opinion Recommending Approval of TUKYSA for Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer-

    -PADCEV U.S. and Global Marketing Applications Planned for 1Q 2021-

    -Tisotumab Vedotin Biologics License Application Submitted to FDA for Recurrent or Metastatic Cervical Cancer-

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

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the fourth quarter and year ended December 31, 2020. The Company also highlighted ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib) commercial and development accomplishments…

    -Net Product Sales of $1 Billion in 2020, an Increase of 59 Percent Over 2019-

    -European Medicines Agency's CHMP Adopted Positive Opinion Recommending Approval of TUKYSA for Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer-

    -PADCEV U.S. and Global Marketing Applications Planned for 1Q 2021-

    -Tisotumab Vedotin Biologics License Application Submitted to FDA for Recurrent or Metastatic Cervical Cancer-

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

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the fourth quarter and year ended December 31, 2020. 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.

    "In 2020, we generated record product revenues of more than $1 billion driven by successful launches of PADCEV and TUKYSA, as well as continued growth of ADCETRIS," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seagen. "These strong results are in addition to several significant business, regulatory and development accomplishments during the year. Looking ahead, we are focused on maximizing the global potential of our approved medicines, advancing our late-stage programs towards securing approvals of new products, and expanding our innovative early-stage pipeline. In collaboration with our partner Genmab we submitted a BLA for tisotumab vedotin to the FDA, positioning it to be our fourth commercial product. We are on track for several other milestones across our pipeline over the course of 2021, and are in a strong financial position to continue executing against our goals."

    COMMERCIAL PRODUCT HIGHLIGHTS

    ADCETRIS

    • Presented 5-year Follow-up Results for ECHELON-1 and ECHELON-2 Trials at the ASH Annual Meeting: Key long-term updates for two phase 3 ADCETRIS trials were presented at the 62nd American Society of Hematology (ASH) annual meeting. Notably, the five-year update of the phase 3 ECHELON-1 clinical trial 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.

    PADCEV

    • Reporting Phase 3 EV-301 and EV-201 Cohort 2 Data in Oral Presentations at ASCO GU; Regulatory Submissions Planned: Full results from the phase 3 EV-301 trial and the second cohort of the pivotal phase 2 EV-201 trial will be presented at the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium (ASCO-GU) being held February 11-13. Both trials were conducted in patients with previously treated locally advanced or metastatic urothelial cancer. The EV-301 data are intended to support global registration submissions planned for the first quarter of 2021. The results from the second cohort of EV-201 will support a supplemental Biologics License Application (BLA) submission with the U.S. Food and Drug Administration (FDA) planned for the first quarter of 2021.
    • Initiated Second Phase 3 Trial in Muscle Invasive Bladder Cancer (MIBC): In collaboration with Astellas and Merck, the randomized phase 3 EV-304/KEYNOTE-B15 trial was initiated to evaluate PADCEV in combination with KEYTRUDA® (pembrolizumab) in cisplatin-eligible MIBC. This is in addition to the ongoing randomized phase 3 study, EV-303/KEYNOTE-905, in cisplatin-ineligible MIBC patients.

    TUKYSA

    • Received Positive CHMP Opinion for TUKYSA: In December 2020, the European Medicines Agency adopted a positive opinion recommending the approval of 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 2 prior anti-HER2 treatment regimens. The CHMP positive opinion is now being considered by the European Commission, which has the authority to approve medicines in the European Union.
    • Presented Multiple TUKYSA Abstracts at SABCS: In December 2020, eight abstracts highlighted Seagen's commitment to addressing unmet needs in breast cancer at the San Antonio Breast Cancer Symposium (SABCS). One presentation provided new exploratory analyses from the pivotal HER2CLIMB trial in metastatic HER2-positive breast cancer that demonstrated progression-free survival, overall survival and objective response rate improvements with TUKYSA were observed consistently across hormone receptor status subgroups, including in patients with brain metastases.

    PIPELINE HIGHLIGHTS

    • Submitted Tisotumab Vedotin BLA to FDA: In February 2021, Seagen and Genmab submitted a BLA to the FDA seeking accelerated approval of tisotumab vedotin for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Results from the innovaTV 204 trial formed the basis of the submission.
    • Initiated Phase 3 Trial of Tisotumab Vedotin: A phase 3 trial, called innovaTV 301, was initiated to evaluate tisotumab vedotin compared to chemotherapy in patients with recurrent or metastatic cervical cancer who have received one or two prior lines of therapy. innovaTV 301 is intended to support global regulatory applications and potentially serve as a confirmatory trial in the U.S.
    • Treated First Patient in Phase 1 Trial of SGN-STNV: In January 2021, the first patient was dosed in a phase 1 trial of SGN-STNV, a novel antibody-drug conjugate (ADC) targeting Sialyl Thomsen-nouveau (STN). STN is highly expressed across multiple solid tumors.

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

    FOURTH QUARTER AND FULL YEAR 2020 FINANCIAL RESULTS

    Revenues: Total revenues in the fourth quarter and year ended December 31, 2020 increased to $601.3 million and $2.2 billion, respectively, compared to $289.8 million and $916.7 million for the same periods in 2019. Revenues were comprised of the following three components:

    • Net Product Sales:

     

    Three months ended December 31,

     

    Full years ended December 31,

    (dollars in millions)

    2020

     

    2019

    % Change

     

    2020

     

    2019

    % Change

    Total Net Product Sales

    $

    294.1

     

     

    $

    166.4

     

    77%

     

    $

    1,000.6

     

     

    $

    628.0

     

    59%

    ADCETRIS

    163.7

     

     

    166.2

     

    (2)%

     

    658.6

     

     

    627.7

     

    5%

    PADCEV

    69.0

     

     

    0.2

     

     

    222.4

     

     

    0.2

     

    TUKYSA

    61.4

     

     

     

    N/A

     

    119.6

     

     

     

    N/A

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

    • Royalty Revenues: Royalty revenues in the fourth quarter were $39.2 million, compared to $72.3 million in the fourth quarter of 2019. The fourth quarter of 2019 included a $40 million milestone from Takeda triggered by annual net sales exceeding $400 million in Takeda's territory during 2019. Royalty revenues were $126.8 million for the full year in 2020, compared to $138.5 million in 2019. Royalty revenues are primarily driven by sales of ADCETRIS outside the U.S. and Canada by Takeda and, to a lesser extent, also include 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 collaboration and license agreements were $267.9 million in the fourth quarter and $1.0 billion for the full year in 2020, compared to $51.1 million and $150.2 million, respectively, for the same periods in 2019. The fourth quarter of 2020 included $250.1 million in revenue related to the premium over market price paid by Merck under a $1 billion stock purchase that closed in October 2020 as part of the ladiratuzumab vedotin collaboration agreement. The full year in 2020 included $975.1 million in license revenue related to the Merck collaborations for ladiratuzumab vedotin and TUKYSA that were entered into in September 2020.

    Cost of Sales: Cost of sales in the fourth quarter were $61.8 million, compared to $11.9 million in the fourth quarter of 2019. Cost of sales were $217.7 million for the full year in 2020, compared to $44.0 million for the same period in 2019. The increases in 2020 were primarily due to the gross profit share payment to Astellas based on PADCEV sales, which were $32.1 million and $104.6 million in the fourth quarter and full year, respectively. Cost of sales for the periods in 2020 also reflect 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. Cost of sales for the year in 2020 included a payment owed to a third-party technology licensor related to the TUKYSA license agreement with Merck reflected in the third quarter of the year.

    Research and Development (R&D) Expenses: R&D expenses in the fourth quarter were $216.2 million, compared to $201.1 million in the fourth quarter of 2019. R&D expenses were $827.1 million for the full year in 2020, compared to $719.4 million in 2019. The increase in 2020 primarily reflected continued investment in the Company's pipeline.

    Selling, General and Administrative (SG&A) Expenses: SG&A expenses in the fourth quarter were $158.4 million, compared to $115.2 million in the fourth quarter of 2019. SG&A expenses were $533.8 million for the full year in 2020, compared to $373.9 million for the same period in 2019. The increases were primarily attributed to increased field sales personnel in the U.S. for Seagen's recently commercialized products, PADCEV and TUKYSA, as well as higher infrastructure costs to support the Company's continued growth and international expansion.

    Non-cash share-based compensation cost for the full year in 2020 was $147.2 million, compared to $127.3 million for the same period in 2019.

    Net Income / Loss: Net income for the fourth quarter of 2020 was $167.1 million, or $0.90 per diluted share, compared to net income of $25.8 million, or $0.14 per diluted share, for the fourth quarter of 2019. For the full year in 2020, net income was $613.7 million, or $3.37 per diluted share, compared to a net loss of $158.7 million, or $0.96 per diluted share, for the year in 2019. Net income for 2020 was driven by the revenue recognized in the third and fourth quarters under the Merck collaborations. Seagen utilized federal net operating loss carryforwards as allowed, however the Company incurred income taxes in certain states which resulted in an income tax provision of $2.0 million for the year in 2020.

    Cash and Investments: As of December 31, 2020, Seagen had $2.7 billion in cash and investments. This includes proceeds from a $1.0 billion equity investment by Merck, which closed in October 2020.

    2021 FINANCIAL OUTLOOK

    Seagen anticipates 2021 revenues, operating expenses and other costs to be in the ranges shown in the table below.

    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 costs1 (primarily attributable to

    share-based compensation)

    $225 million to $245 million

    1. Non-cash costs 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 fourth quarter and full year 2020 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 and supporting slides 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 (U.S.) or 412-717-9224 (international). The conference ID is 10150708. A webcast replay will be archived on the Company's website www.seagen.com, under 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.

    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 and to bring a fourth product to market in the United States; anticipated activities related to the Company's planned and ongoing clinical trials; the opportunities for, and the therapeutic and commercial potential of ADCETRIS, PADCEV, TUKYSA, tisotumab vedotin and the Company's other product candidates and those of its licensees and collaborators; the potential for data from the innovaTV 204 trial to support an 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 Company to commercialize TUKYSA in Europe; 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, government pricing and/or reimbursement actions, market adoption by physicians, impacts associated with COVID-19 or other factors; the risks 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; 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 Exhibit 99.1 to the Company's Current Report on Form 8-K, filed with the Securities and Exchange Commission (SEC) on December 29, 2020, and the Company's subsequent periodic reports 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 applicable law.

    Seagen Inc.

    Condensed Consolidated Statements of Operations

    (Unaudited)

    (In thousands, except per share amounts)

     

    Three Months Ended December 31,

     

    Years Ended December 31,

     

    2020

     

    2019

     

     

    2020

     

     

    2019

     

    Revenues:

     

     

     

     

     

     

     

    Net product sales

    $

    294,125

     

     

    $

    166,414

     

     

     

    $

    1,000,598

     

     

     

    $

    627,977

     

     

    Royalty revenues

    39,236

     

     

    72,273

     

     

     

    126,756

     

     

     

    138,491

     

     

    Collaboration and license agreement revenues

    267,932

     

     

    51,117

     

     

     

    1,048,182

     

     

     

    150,245

     

     

    Total revenues

    601,293

     

     

    289,804

     

     

     

    2,175,536

     

     

     

    916,713

     

     

    Costs and expenses:

     

     

     

     

     

     

     

    Cost of sales

    61,758

     

     

    11,928

     

     

     

    217,720

     

     

     

    43,952

     

     

    Research and development

    216,184

     

     

    201,061

     

     

     

    827,129

     

     

     

    719,374

     

     

    Selling, general and administrative

    158,365

     

     

    115,229

     

     

     

    533,835

     

     

     

    373,932

     

     

    Total costs and expenses

    436,307

     

     

    328,218

     

     

     

    1,578,684

     

     

     

    1,137,258

     

     

    Income (loss) from operations

    164,986

     

     

    (38,414

    )

     

     

    596,852

     

     

     

    (220,545

    )

     

    Investment and other income, net

    898

     

     

    64,244

     

     

     

    18,849

     

     

     

    61,895

     

     

    Income (loss) before income taxes

    165,884

     

     

    25,830

     

     

     

    615,701

     

     

     

    (158,650

    )

     

    Income tax benefit (expense)

    1,211

     

     

     

     

     

    (2,031

    )

     

     

     

     

    Net income (loss)

    $

    167,095

     

     

    $

    25,830

     

     

     

    $

    613,670

     

     

     

    $

    (158,650

    )

     

    Net income (loss) per share - basic

    $

    0.93

     

     

    $

    0.15

     

     

     

    $

    3.51

     

     

     

    $

    (0.96

    )

     

    Net income (loss) per share - diluted

    $

    0.90

     

     

    $

    0.14

     

     

     

    $

    3.37

     

     

     

    $

    (0.96

    )

     

    Shares used in computation of per share amounts - basic

    179,078

     

     

    171,638

     

     

     

    174,834

     

     

     

    165,498

     

     

    Shares used in computation of per share amounts - diluted

    186,040

     

     

    178,501

     

     

     

    182,287

     

     

     

    165,498

     

     

    Seagen Inc.

    Condensed Consolidated Balance Sheets

    (Unaudited)

    (In thousands)

     

    December 31,

     

    2020

     

    2019

    Assets

     

     

     

    Cash, cash equivalents and investments

    $

    2,660,250

     

     

    $

    868,338

     

    Other assets

    1,340,656

     

     

    1,337,528

     

    Total assets

    $

    4,000,906

     

     

    $

    2,205,866

     

    Liabilities and Stockholders' Equity

     

     

     

    Accounts payable and accrued liabilities

    $

    388,138

     

     

    $

    259,357

     

    Long-term liabilities

    124,668

     

     

    70,222

     

    Stockholders' equity

    3,488,100

     

     

    1,876,287

     

    Total liabilities and stockholders' equity

    $

    4,000,906

     

     

    $

    2,205,866

     

     

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  10. - Submission Based on Positive Pivotal innovaTV 204 Trial Results Presented at the European Society of Medical Oncology Virtual Congress 2020 -

    Seagen Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) 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. The submission is based on the results of the innovaTV 204 pivotal phase 2 single-arm clinical trial evaluating tisotumab vedotin as monotherapy in this setting. The topline results from the phase 2 study…

    - Submission Based on Positive Pivotal innovaTV 204 Trial Results Presented at the European Society of Medical Oncology Virtual Congress 2020 -

    Seagen Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) 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. The submission is based on the results of the innovaTV 204 pivotal phase 2 single-arm clinical trial evaluating tisotumab vedotin as monotherapy in this setting. The topline results from the phase 2 study were announced in June 2020 and data were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. 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

    "In the pivotal phase 2 study, tisotumab vedotin induced clinically meaningful and durable responses in this difficult to treat cervical cancer patient population, with a manageable and tolerable safety profile. Today's submission marks an important milestone for tisotumab vedotin and a potential advance for patients with recurrent or metastatic cervical cancer for whom there is a high unmet need for effective new therapies," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "We look forward to working with the FDA on the review of the application."

    "This BLA submission is an important step toward our goal of improving the lives of women with recurrent or metastatic cervical cancer. I would like to thank the patients, nurses, physicians and researchers who participated in the innovaTV 204 trial, which is the basis of this submission," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We believe, if approved, tisotumab vedotin as monotherapy has the potential to become an important treatment option for women with recurrent or metastatic cervical cancer, who have disease progression on or after chemotherapy."

    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 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. ADCETRIS® (brentuximab vedotin) and PADCEV® (enfortumab vedotin-ejfv) use the Company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSA® (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our 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.

    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, clinical trials of tisotumab vedotin and its therapeutic potential. 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 the Biologics License Application submission based on the innovaTV 204 trial may not be accepted for filing by, or 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 as tisotumab vedotin advances in clinical trials even after promising results in earlier clinical trials. 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 September 30, 2020 and the Company's Current Report on Form 8-K dated December 30, 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.

    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®. Arzerra® and Kesimpta® are trademarks of Novartis AG or its affiliates. DARZALEX® and DARZALEX FASPRO® are trademarks of Janssen Pharmaceutica NV. TEPEZZA® is a trademark of Horizon Therapeutics plc.

    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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  11. Seagen Inc. (NASDAQ:SGEN) today announced that it will report its fourth quarter and full year 2020 financial results on Thursday, February 11, 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 general corporate update. Access to the event can be obtained as follows:

    Thursday, February 11, 2021

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

    • Telephone 844-763-8274 (domestic) or +1 412-717-9224 (international); conference ID 10150708
    • 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…

    Seagen Inc. (NASDAQ:SGEN) today announced that it will report its fourth quarter and full year 2020 financial results on Thursday, February 11, 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 general corporate update. Access to the event can be obtained as follows:

    Thursday, February 11, 2021

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

    • Telephone 844-763-8274 (domestic) or +1 412-717-9224 (international); conference ID 10150708
    • 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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  12. Seagen Inc. (NASDAQ:SGEN) today announced that management will present at the 39th Annual J.P. Morgan Virtual Healthcare Conference on Monday, January 11, 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

    Seagen Inc. (NASDAQ:SGEN) today announced that management will present at the 39th Annual J.P. Morgan Virtual Healthcare Conference on Monday, January 11, 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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  13. Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, today announced that Natasha A. Hernday has joined Alpine's Board of Directors. Ms. Hernday brings more than 20 years of experience in corporate development and corporate strategy.

    "I'm delighted to welcome Natasha to Alpine Immune Sciences' Board at this important moment in our company's history, as we build on our strategic partnership with AbbVie and leverage Alpine's financial strength to further advance our development pipeline," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine. "I look forward to benefiting from Natasha's…

    Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, today announced that Natasha A. Hernday has joined Alpine's Board of Directors. Ms. Hernday brings more than 20 years of experience in corporate development and corporate strategy.

    "I'm delighted to welcome Natasha to Alpine Immune Sciences' Board at this important moment in our company's history, as we build on our strategic partnership with AbbVie and leverage Alpine's financial strength to further advance our development pipeline," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine. "I look forward to benefiting from Natasha's extensive experience and acumen as we oversee the next stages of Alpine's growth to the benefit of Alpiners, shareholders and patients alike."

    Ms. Hernday currently serves as Executive Vice President, Corporate Development and as a member of the Executive Committee for the publicly traded biotechnology company Seagen, Inc. (NASDAQ:SGEN). Since joining Seagen in 2011, Ms. Hernday has built and led the business development team responsible for licensing deals, acquisitions and strategic alliances. From 1994 through 2010, after starting her career in molecular and mammalian cell biology, Ms. Hernday served in various roles of increasing responsibility at Amgen Inc., including as Director, Mergers & Acquisitions and as Director, Out-Partnering. She also serves on the board of directors of Xoma Corp. (NASDAQ:XOMA) and PDL BioPharma, Inc. (NASDAQ:PDLI), and on the Knight Campus External Advisory Board for the University of Oregon.

    Ms. Hernday received her BA in microbiology from the University of California at Santa Barbara and MBA from Pepperdine University.

    Concurrent with Ms. Hernday joining Alpine's Board of Directors, the company also announced that Paul Sekhri will be stepping down as a director of the company. Mr. Sekhri has served on Alpine's Board of Directors since February 2016.

    Mitchell H. Gold commented, "On behalf of the Board and Alpine's executive team, I would like to thank Paul for the service he has provided to the company and wish him well in any and all future endeavors."

    About Alpine Immune Sciences, Inc.

    Alpine Immune Sciences, Inc. is committed to leading a new wave of immune therapeutics. With world-class research and development capabilities, a highly productive scientific platform, and a proven management team, Alpine is creating multifunctional immunotherapies via unique protein engineering technologies designed to improve patients' lives. Alpine has entered into strategic collaborations with leading global biopharmaceutical companies and has a diverse pipeline of clinical and preclinical candidates in development. For more information, visit www.alpineimmunesciences.com. Follow @AlpineImmuneSci on Twitter and LinkedIn.

    Forward-Looking Statements

    This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding our platform technology and potential therapies, the future development plans and commercial potential of our product candidates, the progress and potential of our other ongoing development programs, and our ability to successfully develop and achieve milestones in our development programs. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions and include words such as "may," "will," "should," "would," "expect," "plan," "intend," and other similar expressions, among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties, and other factors that may cause actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: the impact of the COVID-19 pandemic on our business, research and clinical development plans and timelines and results of operations; our discovery-stage and preclinical programs may not advance into the clinic or result in approved products; any of our product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; as well as the other risks identified in our filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and we undertake no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.

    "Secreted Immunomodulatory Proteins", "SIP", "Transmembrane Immunomodulatory Protein," "TIP," "Variant Ig Domain," "vIgD" and the Alpine logo are registered trademarks or trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

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  14. - Recommendation for Approval in the European Union Based on Results of Pivotal HER2CLIMB Trial -

    Seagen Inc. (NASDAQ:SGEN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion recommending the approval of TUKYSA® (tucatinib) 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 2 prior anti-HER2 treatment regimens. TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.1,2

    The CHMP positive opinion will now be considered by the European Commission (EC), which has the…

    - Recommendation for Approval in the European Union Based on Results of Pivotal HER2CLIMB Trial -

    Seagen Inc. (NASDAQ:SGEN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion recommending the approval of TUKYSA® (tucatinib) 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 2 prior anti-HER2 treatment regimens. TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.1,2

    The CHMP positive opinion will now be considered by the European Commission (EC), which has the authority to approve medicines in the European Union (EU). TUKYSA is approved in the United States, Canada, Switzerland, Singapore and Australia.

    "We are pleased the CHMP has recognized TUKYSA as a meaningful clinical advance for people with advanced HER2-positive metastatic breast cancer, including those with cancer that has spread to the brain," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "This opinion brings us one step closer to making TUKYSA available to patients in the EU and aligns with our commitment to bring innovative therapies to patients around the world."

    The positive CHMP opinion is based on results of the pivotal trial HER2CLIMB and were published in The New England Journal of Medicine in December 2019.

    About HER2CLIMB

    HER2CLIMB is a randomized, double-blind, placebo-controlled, active comparator, global trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). The results for the primary endpoint showed patients who received TUKYSA in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (PFS) compared to patients who received trastuzumab and capecitabine alone (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001). A secondary endpoint showed that the addition of TUKYSA reduced the risk of death (OS) by 34 percent compared to trastuzumab and capecitabine alone (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048). Based on the results, TUKYSA was approved in the U.S. in combination with trastuzumab and capecitabine for treatment of 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.

    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.3 Between 15 and 20 percent of breast cancer cases are HER2-positive.4 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.5,4,6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.7,8,9

    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.1

    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 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. 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 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 September 30, 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 https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-tukysa_en.pdf

    2 Anita Kulukian, Patrice Lee, Janelle Taylor, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor ModelsMol Cancer Ther 2020;19:976-987.

    3 Breast. Globocan 2018. World Health Organization. 2019. https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf

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

    6 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.

    7 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.

    8 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.

    9 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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  15. - New analyses from the pivotal HER2CLIMB trial describe outcomes by hormone receptor status -

    Seagen Inc. (NASDAQ:SGEN) today announced the presentation of new data from TUKYSA (tucatinib), its HER2-positive metastatic breast cancer therapy, at the San Antonio Breast Cancer Symposium (SABCS) Virtual Symposium, taking place December 8-11, 2020. Nine abstracts – including two spotlight posters – highlight the company's commitment to addressing unmet needs in breast cancer.

    "Following this year's FDA approval of TUKYSA, we continue to broadly study if more patients may benefit from this important medicine," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Data presented at the meeting from the HER2CLIMB trial demonstrate TUKYSA's…

    - New analyses from the pivotal HER2CLIMB trial describe outcomes by hormone receptor status -

    Seagen Inc. (NASDAQ:SGEN) today announced the presentation of new data from TUKYSA (tucatinib), its HER2-positive metastatic breast cancer therapy, at the San Antonio Breast Cancer Symposium (SABCS) Virtual Symposium, taking place December 8-11, 2020. Nine abstracts – including two spotlight posters – highlight the company's commitment to addressing unmet needs in breast cancer.

    "Following this year's FDA approval of TUKYSA, we continue to broadly study if more patients may benefit from this important medicine," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Data presented at the meeting from the HER2CLIMB trial demonstrate TUKYSA's efficacy regardless of patients' hormone receptor status, while other clinical and preclinical findings provide new insights about TUKYSA's potential to help patients living with HER2-positive metastatic breast cancer."

    Highlights for key data presentations at the meeting include:

    Efficacy Outcomes by Hormone Receptor Status from HER2CLIMB Trial

    Outcomes for TUKYSA® (tucatinib) in combination with trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer from the pivotal HER2CLIMB trial by hormone receptor (HR) status will be featured in a spotlight poster (Abstract #PD3-08). Results will be presented by Erika P. Hamilton, M.D., Director, Breast Cancer and Gynecologic Cancer Research Program at the Sarah Cannon Research Institute.

    As previously reported, the addition of TUKYSA to trastuzumab and capecitabine resulted in clinically meaningful improvements in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) compared to the addition of placebo. The new exploratory analyses presented at SABCS demonstrated that the PFS, OS and ORR improvements with TUKYSA were observed consistently across hormone receptor status subgroups, including in patients with brain metastases.

    SABCS 2020 Data Presentations for Seagen Medicines and Pipeline Agents:

    Below are presentation details related to TUKYSA and the investigational agent ladiratuzumab vedotin at SABCS. Published abstracts can be found here. Poster presentations will be available on December 9, 2020.

    Abstract Title

    Abstract No.

    Presentation

    Type / Date

    Presenter

    Tucatinib versus placebo in combination with trastuzumab and capecitabine for patients with locally advanced unresectable or HER2-positive metastatic breast cancer (HER2CLIMB): outcomes by hormone receptor status

    #PD3-08

    Spotlight Poster Discussion 3 – Wednesday, Dec. 9 from 6:45 - 7:45 p.m. CT

    E. Hamilton

    Impact of tucatinib on health-related quality of life in patients with HER2+ metastatic breast cancer with stable and active brain metastases

    #PD13-04

    Spotlight Poster Discussion 13 – Friday, Dec. 11 from 1 – 2:15 p.m. CT

    A. Wardley

    Tucatinib favourably modulates the immune microenvironment and synergises with anti-PD1 therapy in a trastuzumab resistant HER2+ murine model

    #PS10-04

    Poster Session 10 / Wednesday, Dec. 9 at 8 a.m. CT

    R. Li

    Tucatinib potentiates the activity of the antibody-drug conjugate T-DM1 in preclinical models of HER2-positive breast cancer

    #PS10-08

    Poster Session 10 / Wednesday, Dec. 9 at 8 a.m. CT

    A. Kulukian

    Real world treatment patterns and healthcare resource utilization among HER2+ metastatic breast cancer patients with and without brain metastases: a retrospective cohort study

    #PS14-15

    Poster Session 14 / Wednesday, Dec. 9 at 8 a.m. CT

    C. Ike

    Interim safety and efficacy analysis of phase IB/II clinical trial of tucatinib, palbociclib and letrozole in patients with hormone receptor and HER2-positive metastatic breast cancer

    #PS10-03

    Poster Session 10 / Wednesday, Dec. 9 at 8 a.m. CT

    E. Shagisultanova

    Trials-in-Progress

    HER2CLIMB-02: A randomized, double-blind, phase 3 study of tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer

    #OT-28-01

    Ongoing Trials Posters / Wednesday, Dec. 9 at 8 a.m. CT

    S. Hurvitz

    SGNLVA-001: a phase 1 open-label dose escalation and expansion study of SGN-LIV1A administered weekly in breast cancer

    #OT-03-03

    Ongoing Trials Posters / Wednesday, Dec. 9 at 8 a.m. CT

    H.C. Beckwith

    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. In the U.S., TUKYSA is approved in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases (disease that has spread to the brain), who have received one or more prior anti-HER2-based regimens in the metastatic setting. TUKYSA is approved in the U.S., Switzerland, Canada, Singapore and Australia and is under review in the European Union. As part of a strategic collaboration announced in September 2020 with Merck, known as MSD outside the United States and Canada, Merck has exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe.

    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 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. 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 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 September 30, 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.

    View Full Article Hide Full Article
  16. - Five-Year Update of the ECHELON-1 Clinical Trial Shows Treatment with ADCETRIS in Combination with AVD Chemotherapy Results in Superior Long-Term Outcomes when Compared to ABVD in Frontline Advanced Hodgkin Lymphoma -

    - Five-Year Results of the ECHELON-2 Clinical Trial Continue to Demonstrate Significant Durable Improvement in Progression-Free Survival and Overall Survival of ADCETRIS Plus CHP Chemotherapy when Compared to CHOP in Frontline Peripheral T-Cell Lymphoma -

    - Nineteen Presentations Across Seagen Programs, Including First Results from Phase 2 Clinical Trial of ADCETRIS plus Opdivo® (Nivolumab) in Mediastinal Gray Zone Lymphoma -

    Seagen Inc. (NASDAQ:SGEN) today announced multiple ADCETRIS® (brentuximab vedotin) data presentations…

    - Five-Year Update of the ECHELON-1 Clinical Trial Shows Treatment with ADCETRIS in Combination with AVD Chemotherapy Results in Superior Long-Term Outcomes when Compared to ABVD in Frontline Advanced Hodgkin Lymphoma -

    - Five-Year Results of the ECHELON-2 Clinical Trial Continue to Demonstrate Significant Durable Improvement in Progression-Free Survival and Overall Survival of ADCETRIS Plus CHP Chemotherapy when Compared to CHOP in Frontline Peripheral T-Cell Lymphoma -

    - Nineteen Presentations Across Seagen Programs, Including First Results from Phase 2 Clinical Trial of ADCETRIS plus Opdivo® (Nivolumab) in Mediastinal Gray Zone Lymphoma -

    Seagen Inc. (NASDAQ:SGEN) today announced multiple ADCETRIS® (brentuximab vedotin) data presentations at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually December 5-8, 2020. Data presentations include five-year updates from the phase 3 ECHELON-1 and ECHELON-2 clinical trials evaluating ADCETRIS plus a chemotherapy combination regimen in frontline advanced stage classical Hodgkin lymphoma (HL) and CD30-expressing frontline peripheral T-cell lymphoma (PTCL), respectively. In addition, first results were presented from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with Opdivo® (nivolumab) in relapsed or refractory mediastinal gray zone lymphoma (MGZL), a rare type of non-Hodgkin lymphoma that express CD30 with no standard of care. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and expressed on the surface of several types of non-Hodgkin lymphoma, including PTCL. ADCETRIS is being evaluated globally in more than 70 corporate- and investigator-sponsored clinical trials across multiple settings in lymphoma and other indications. ADCETRIS and Opdivo are not approved alone or in combination for the treatment of relapsed or refractory MGZL.

    "After five years of follow-up, an important clinical milestone, both the ECHELON-1 and ECHELON-2 clinical trials demonstrate that ADCETRIS plus chemotherapy resulted in superior and durable outcomes when compared with standard chemotherapy regimens," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "As most relapses in Hodgkin lymphoma occur within five years of frontline treatment, the results of the ECHELON-1 study suggest that patients treated with ADCETRIS plus chemotherapy are more likely to experience long-term remissions compared to those treated with the ABVD regimen."

    Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study (Abstract #2973, poster presentation on Monday, December 7, 2020)

    The ECHELON-1 clinical trial is evaluating ADCETRIS in combination with AVD (Adriamycin [doxorubicin], vinblastine, dacarbazine) compared to ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) in patients with Stage III or IV frontline classical HL. As previously reported, the ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified progression-free survival (PFS) compared to the control arm of ABVD as assessed by independent review facility (IRF; hazard ratio (HR), 0.77; p=0.035). A five-year exploratory analysis was conducted to examine PFS outcomes per investigator assessment in the intent-to-treat population of 1,334 patients. Results include:

    • Patients in the ADCETRIS plus AVD arm had a 32 percent reduction in the risk of a progression event compared to patients in the ABVD arm. The five-year PFS rate for patients in the ADCETRIS plus AVD arm was 82.2 percent compared to 75.3 percentin the ABVD arm, an absolute difference of 6.9 percent (HR, 0.681 [95% CI: 0.534, 0.867]). Median follow-up time was 60.9 months.
    • Consistent benefit in PFS was observed among patients treated with ADCETRIS plus AVD compared with ABVD, independent of disease stage, age and prognostic score.
      • Consistent improvements compared to ABVD were observed in patients with Stage III (HR, 0.593; [95% CI: 0.385, 0.915]) and Stage IV (HR, 0.731; [95% CI: 0.545, 0.980]) disease.
    • As previously reported for the primary analysis, on the ADCETRIS plus AVD arm, peripheral neuropathy events were observed in 67 percent of patients compared to 43 percent in the ABVD arm. The five-year update shows that among patients with peripheral neuropathy, 85 percent in the ADCETRIS plus AVD arm and 86 percent in the ABVD arm reported complete resolution or improvement at last follow-up.
    • There were fewer secondary malignancies in the ADCETRIS plus AVD arm. Among 48 patients with reported secondary malignancies, 19 [(nine hematological malignancies and 10 solid tumors)] were in the ADCETRIS plus AVD arm and 29 [(15 hematological malignancies and 14 solid tumors)] were in the ABVD arm.
    • There were a higher number of pregnancies in the ADCETRIS plus AVD arm compared to the ABVD arm. A total of 150 pregnancies were reported among study participants and their partners, including 89 on the ADCETRIS plus AVD arm and 61 on the ABVD arm.

    The ECHELON-2 Trial: 5-Year Results of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in Frontline Treatment of Patients with CD30-Positive Peripheral T-Cell Lymphoma (Abstract #1150, poster presentation on Saturday, December 5, 2020)

    The ECHELON-2 clinical trial is evaluating ADCETRIS in combination with CHP (cyclophosphamide, Adriamycin [doxorubicin], prednisone) compared to CHOP (cyclophosphamide, Adriamycin [doxorubicin], vincristine, prednisone) in frontline CD30-expressing PTCL. As previously reported, the ECHELON-2 trial met its primary endpoint with the combination of ADCETRIS plus CHP resulting in a statistically significant improvement in PFS versus the control arm of CHOP per blinded independent central review (HR, 0.71; p=0.0110). A five-year post-hoc exploratory analysis was conducted to examine PFS outcome and overall survival (OS) per investigator assessment in the intent-to-treat population of 452 patients. Key findings include:

    • Patients in the ADCETRIS plus CHP arm had a 30 percent reduction in the risk of a progression event compared to patients in the CHOP arm. The five-year PFS rate for patients in the ADCETRIS plus CHP arm was 51.4 percent compared to 43 percent in the CHOP arm, an absolute difference of 8.4 percent (HR, 0.70 [95% CI: 0.53, 0.91]).
    • OS in the ADCETRIS plus CHP arm was improved compared to CHOP (HR=0.72 [95% CI: 0.53, 0.99]). This represents a 28 percent reduction in the risk of death. Median follow-up time was 66.8 months.
    • Among 316 systemic anaplastic large-cell lymphoma (sALCL) patients on study, patients in the ADCETRIS plus CHP arm had a 45 percent reduction in the risk of a progression event compared to patients in the CHOP arm (HR, 0.55 [95% CI: 0.39, 0.79]). There was a 34 percent reduction in the risk of death. Median follow-up time for PFS was 42.7 months.
    • Consistent improvement in both PFS and OS was observed among patients treated with ADCETRIS plus CHP arm compared to the CHOP arm across the majority of pre-specified subgroups.
    • The five-year update shows that among patients with peripheral neuropathy, 72 percent in the ADCETRIS plus CHP arm and 78 percent in the CHOP arm reported complete resolution or improvement at last follow-up. For ongoing peripheral neuropathy events, 98 percent in the ADCETRIS plus CHP arm and 98 percent in the CHOP arm were Grade 1 or 2.

    Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Mediastinal Gray Zone Lymphoma: Primary Efficacy and Safety Analysis of the Phase 2 CheckMate 436 Study (Abstract #2045, poster presentation on Sunday, December 6, 2020)

    Data from the ongoing CheckMate 436 phase 2 clinical trial of 10 patients with relapsed or refractory MGZL who received a combination of ADCETRIS plus Opdivo treatment after autologous stem cell transplant or two or more lines of multi-agent chemotherapy if ineligible for transplant will be presented for the first time. Patients were treated once every three weeks or until disease progression or unacceptable toxicity. The median age of patients was 35 years. Key findings include:

    • Of 10 response-evaluable patients, seven patients (70 percent) had an objective response, including five patients (50 percent) with a complete response and two patients (20 percent) with a partial response. Two patients (20 percent) had progressive disease and in one patient (10 percent) death occurred prior to disease assessment.
    • Median follow-up time was 12.4 months. Time to complete response was 1.2-4.8 months and the duration was 1.5+ to 3.2+ months before patients were assessed for subsequent therapy. All patients who achieved a complete response underwent a hematopoietic cell transplant and follow-up is ongoing.
    • The most common adverse events of any grade in at least 20 percent of patients were neutropenia and paresthesia (30 percent each); thrombocytopenia, anemia and peripheral sensory neuropathy (20 percent each). The most common Grade 3 adverse events were neutropenia and thrombocytopenia (10 percent each). Three patient deaths occurred due to disease progression.

    About ADCETRIS

    ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagen's proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing cells.

    ADCETRIS for injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

    Health Canada granted ADCETRIS approval with conditions in 2013 for patients with (1) HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates and (2) sALCL after failure of at least one multi-agent chemotherapy regimen. Non-conditional approval was granted for (3) post-ASCT consolidation treatment of patients with HL at increased risk of relapse or progression in 2017, (4) adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy in 2018, (5) for previously untreated patients with Stage IV HL in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and (6) for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.

    ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (4) for the treatment of adult patients with previously untreated sALCL in combination with cyclophosphamide, doxorubicin and prednisone (CHP), (5) for the treatment of adult patients with relapsed or refractory sALCL, and (6) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

    ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See U.S. important safety information, including Boxed Warning, below.

    Seagen and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

    ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

    BOXED WARNING

    PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

    Contraindication

    ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

    Warnings and Precautions

    • Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.
    • Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.
    • Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.

    Administer G-CSF primary prophylaxis beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.

    Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

    • Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for bacterial, fungal, or viral infections.
    • Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
    • Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid use in patients with severe renal impairment.
    • Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment.
    • Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
    • PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
    • Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
    • Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
    • Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.
    • Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.
    • Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

    Most Common (≥20% in any study) Adverse Reactions

    Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

    Drug Interactions

    Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE).

    Use in Specific Populations

    Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

    Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

    Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

    Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS 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 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 therapeutic potential of ADCETRIS plus chemotherapy combination regimens in frontline advanced stage Hodgkin lymphoma, and frontline peripheral T-cell lymphoma, and in combination with Opdivo® (nivolumab) in relapsed or refractory mediastinal gray zone lymphoma (MGZL). Actual results or developments may differ materially from those projected or implied in these forward-looking statements due to factors such as unexpected adverse events, adverse regulatory actions, the degree of utilization and adoption of an approved treatment regimen by prescribing physicians, the difficulty and uncertainty of pharmaceutical product development, negative or disappointing clinical trial results and risks related to the duration and severity of the COVID-19 pandemic. 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 September 30, 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. - Presentations Demonstrate Ability of Seagen Antibody-Drug Conjugates to Elicit Immunogenic Cell Death Effect Across Multiple Tumor Types -

    - Data Features Seagen's Sugar-Engineered Antibodies as part of an Emerging, Innovative Immuno-Oncology Pipeline -

    Seagen Inc. (NASDAQ:SGEN) today announced the presentation of immuno-oncology data from its broad pipeline of therapies at the Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting 2020, taking place virtually November 9-14, 2020. Six abstracts will highlight the company's continued progress in advancing innovative research for marketed and late-stage antibody-drug conjugates (ADCs) and innovative empowered antibody pipeline utilizing its proprietary sugar-engineering…

    - Presentations Demonstrate Ability of Seagen Antibody-Drug Conjugates to Elicit Immunogenic Cell Death Effect Across Multiple Tumor Types -

    - Data Features Seagen's Sugar-Engineered Antibodies as part of an Emerging, Innovative Immuno-Oncology Pipeline -

    Seagen Inc. (NASDAQ:SGEN) today announced the presentation of immuno-oncology data from its broad pipeline of therapies at the Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting 2020, taking place virtually November 9-14, 2020. Six abstracts will highlight the company's continued progress in advancing innovative research for marketed and late-stage antibody-drug conjugates (ADCs) and innovative empowered antibody pipeline utilizing its proprietary sugar-engineering antibody (SEA) technology.

    Data presented at SITC will demonstrate how Seagen's monomethyl auristatin E (MMAE)-based ADCs induce immunogenic cell death (ICD) by activating the innate immune cells and changing the tumor microenvironment to a more inflammatory state thereby enhancing the efficacy of other cancer immunotherapies. These findings will be presented for tisotumab vedotin, ladiratuzumab vedotin and across vedotin-based ADCs (Abstracts #617, #618 and #323).

    "Our vedotin-based ADC research at SITC illustrates the impact of immunogenic cell death on the tumor microenvironment," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Importantly, these data support the mechanistic rationale for combining vedotin-based ADCs with immuno-oncology therapies in the clinic."

    Data will also be presented utilizing Seagen's proprietary SEA technology, which produces nonfucosylated antibodies that uniquely enhance activity targeting key immune modulating receptors. Preclinical data will be presented from SEA-TGT (Abstract #250), a novel investigational nonfucosylated human IgG1 TIGIT antibody. SEA-TGT is in an ongoing phase 1 clinical trial for patients with solid tumors and lymphoma (NCT04254107). In addition, preclinical data will be presented for SEA-CD40 (Abstract #438), a novel investigational, nonfucosylated human IgG1 antibody targeted to CD40, an immune stimulatory receptor found on antigen-presenting cells. SEA-CD40 is in a phase 1 trial for pancreatic cancer in combination with chemotherapy and a PD-1 inhibitor (NCT02376699).

    "We believe our immuno-oncology candidates have a best-in-class potential, creating a strong foundation for our immunotherapy pipeline," said Scott Peterson, Ph.D., Senior Vice President of Research at Seagen. "Data presented at SITC demonstrate that our sugar-engineered antibodies are differentiated and have the potential to improve efficacy and address unmet needs in cancer."

    Data regarding ADCETRIS® (brentuximab vedotin) will be presented demonstrating its ability to selectively target and kill CD30-positive T regulatory cells (Tregs) that contribute to resistance to cancer immunotherapies (Abstract #696). These data support that ADCETRIS may have an immunomodulatory effect through selective depletion of highly active Tregs.

    The abstracts published in advance of the SITC Annual Meeting can be found here. All data presentations will be available on-demand starting on November 11, 2020.

    Details of Seagen Presentations at SITC Annual Meeting 2020:

    Abstract Title

    Abstract No.

    Presentation

    Type / Date

    Presenter

    Brentuximab vedotin, a CD30 targeting antibody-drug conjugate, selectively depletes activated Tregs in vitro and in vivo

    #696

    E-Poster /

    November 11-14

    B. Grogan

    Tisotumab vedotin shows immunomodulatory activity through induction of immunogenic cell death

    #617

    E-Poster /

    November 11-14

    E. Gray

    Systemic administration of ladiratuzumab vedotin alone or in combination with pembrolizumab results in significant immune activation in the tumor microenvironment in metastatic breast cancer patients

    #323

    E-Poster /

    November 11-14

    L. Pusztai

    Synergy between SEA-CD40 and chemotherapeutics drives curative anti-tumor activity in pre-clinical models

    #438

    E-Poster /

    November 11-14

    W. Zeng

    SEA-TGT is a nonfucosylated antibody with distinct and amplified effector function activity that leverages the dependencies of anti-TIGIT anti-tumor activity upon FcγR engagement

    #250

    E-Poster /

    November 11-14

    A. Smith

    Vedotin ADCs induce ER stress and elicit hallmarks of ICD across multiple cancer indications

    #618

    E-Poster /

    November 11-14

    K. Klussman

    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 ability of vedotin-based ADCs to enhance the efficacy of immune-oncology therapies, the potential of the Company's SEA-TGT and SEA-CD40 product candidates and the potential of the Company's immunotherapy 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 the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the inability to show sufficient activity 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 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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  18. - Five-Year Update to be Presented from ADCETRIS Phase 3 ECHELON-1 and ECHELON-2 Clinical Trials -

    - Additional Data Analyses Highlight Activities Across Broad ADCETRIS Development Program -

    Seagen Inc. (NASDAQ:SGEN) today announced multiple ADCETRIS® (brentuximab vedotin) data presentations at the upcoming 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually December 5-8, 2020. Data presentations will include five-year updates from the phase 3 ECHELON-1 and ECHELON-2 clinical trials evaluating ADCETRIS plus a chemotherapy combination regimen in frontline advanced stage Hodgkin lymphoma (HL) or frontline peripheral T-cell lymphoma (PTCL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30…

    - Five-Year Update to be Presented from ADCETRIS Phase 3 ECHELON-1 and ECHELON-2 Clinical Trials -

    - Additional Data Analyses Highlight Activities Across Broad ADCETRIS Development Program -

    Seagen Inc. (NASDAQ:SGEN) today announced multiple ADCETRIS® (brentuximab vedotin) data presentations at the upcoming 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually December 5-8, 2020. Data presentations will include five-year updates from the phase 3 ECHELON-1 and ECHELON-2 clinical trials evaluating ADCETRIS plus a chemotherapy combination regimen in frontline advanced stage Hodgkin lymphoma (HL) or frontline peripheral T-cell lymphoma (PTCL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and expressed on the surface of several types of PTCL. ADCETRIS is being evaluated globally in more than 70 corporate- and investigator-sponsored clinical trials across multiple settings in lymphoma and other indications.

    "At this year's ASH meeting, ADCETRIS will be featured in 18 data presentations, including five-year analyses from the ECHELON-1 and ECHELON-2 phase 3 frontline trials," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Reaching five-years without disease recurrence represents a significant clinical milestone for patients, as they may be considered disease-free at this time point. The five-year data presentations from our phase 3 ECHELON-1 and ECHELON-2 trials demonstrate ADCETRIS plus chemotherapy resulted in superior clinical activity and durable benefit when compared to outcomes with a standard chemotherapy regimen. We will also present additional analyses from trials evaluating ADCETRIS in combination with other therapies, with the goal of identifying potential new treatment strategies that improve outcomes for patients."

    Details of Seagen Presentations at ASH:

    Abstract Title

    Abstract #

    Presentation

    Type / Date

    Presenter

    Company-Sponsored Trials

    Frontline Brentuximab Vedotin as Monotherapy or in Combination for Older Hodgkin Lymphoma Patients

    #471

    Oral presentation / Sunday, Dec. 6 at 2:15 p.m. PT

    C. Yasenchak

    Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin lymphoma: 5-year Update of the ECHELON-1 Study

    #2973

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    D. Straus

    The ECHELON-2 Trial: 5-Year Results of a Randomized, Double-Blind, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in Frontline Treatment of Patients with CD30-positive Peripheral T-cell Lymphoma

    #1150

    Poster presentation / Saturday, Dec. 5, 7:00 a.m. - 3:30 p.m. PT

    S. Horwitz

    Economic Assessment of Diagnostic Revision in Peripheral T-cell Lymphoma

    #1606

    Poster presentation / Saturday, Dec. 5, 7:00 a.m. - 3:30 p.m. PT

    N. Liu

    Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Mediastinal Gray Zone Lymphoma: Primary Efficacy and Safety Analysis of the Phase 2 CheckMate 436 Study

    #2045

    Poster presentation / Sunday, Dec. 6, 7:00 a.m. - 3:30 p.m. PT

    A. Santoro

    Real-World Characteristics of Patients with Classical Hodgkin Lymphoma Receiving Frontline Brentuximab Vedotin with Chemotherapy: A Retrospective Analysis with Propensity Score Matching

    #2499

    Poster presentation / Sunday, Dec. 6, 7:00 a.m. - 3:30 p.m. PT

    T. Phillips

    Real-World Adherence to National Comprehensive Cancer Network (NCCN) Guidelines Regarding the Usage of PET/CT and Reported Deauville Scores in Advanced Stage Classical Hodgkin Lymphoma: A Community Oncology Practice Perspective

    #2033

    Poster presentation / Sunday, Dec. 6, 7:00 a.m. - 3:30 p.m. PT

    C. Yasenchak

    SGN-CD30C, an Investigational CD30-Directed Camptothecin Antibody-Drug Conjugate (ADC), Shows Strong Anti Tumor Activity and Superior Tolerability in Preclinical Studies

    #2089

    Poster presentation / Sunday, Dec. 6, 7:00 a.m. - 3:30 p.m. PT

    M. Ryan

    Real-World Characteristics of Patients with Peripheral T-Cell Lymphoma Receiving Frontline Brentuximab Vedotin with Chemotherapy: A Retrospective Analysis with Propensity Score Matching

    #3418

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    J. Burke

    Nodal Peripheral T-Cell Lymphoma with T Follicular-Helper Phenotype: A Different Entity? Results of the Spanish Retrospective Real-T Study

    #2972

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    AM. Garcia-Sancho

    Results from the International, Multi-Center, Retrospective B-Holistic Study: Describing Treatment Pathways and Outcomes for Classical Hodgkin Lymphoma

    #2979

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    B. Ferhanoglu

    Investigator-Sponsored Trials

    Increased Tumor Specific Cytotoxic T Cell Responses and Reversion to a Favorable Cytokine Profile after Treatment in Patients with Newly Diagnosed High Risk Hodgkin Lymphoma Treated on Children's Oncology Group Trial- AHOD1331

    #595

    Oral presentation / Monday, Dec. 7 at 9:15 a.m. PT

    H. Dave

    Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Results of a LYSA Multicenter, Phase II Study. "The TOTAL Trial"

    #1161

    Poster presentation / Saturday, Dec. 5, 7:00 a.m. - 3:30 p.m. PT

    O. Tournilhac

    A Pilot Study of Brentuximab Vedotin, Rituximab and Dose Attenuated CHP in Patients 75 Years and Older with Diffuse Large B-Cell Lymphoma

    #2102

    Poster presentation / Sunday, Dec. 6, 7:00 a.m. - 3:30 p.m. PT

    P. Reagan

    Dose-Dense Brentuximab Vedotin Plus Ifosfamide, Carboplatin, and Etoposide (ICE) Is Highly Active for Second Line Treatment in Relapsed/Refractory Classical Hodgkin Lymphoma: Final Results of a Phase I/II Study

    #2964

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    R. Lynch

    A Phase I Trial Assessing the Feasibility of Romidepsin Combined with Brentuximab Vedotin for Patients Requiring Systemic Therapy for Cutaneous T-Cell Lymphoma

    #2970

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    S. Barta

    Trials-in-Progress

    Trial-in-Progress: Brentuximab Vedotin in Combination with Lenalidomide and Rituximab in Subjects with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

    #2112

    Poster presentation / Sunday, Dec. 6, 7:00 a.m. - 3:30 p.m. PT

    N. Bartlett

    A Phase 1 Study of Sea-CD70 in Myeloid Malignancies

    #2874

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    A. Aribi

    Trial-in-Progress: Frontline Brentuximab Vedotin and CHP (A+CHP) in Patients with Peripheral T-Cell Lymphoma with Less Than 10% CD30 Expression

    #2976

    Poster presentation / Monday, Dec. 7, 7:00 a.m. - 3:30 p.m. PT

    D. Jagadeesh

    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 therapeutic potential of ADCETRIS plus chemotherapy combination regimens in frontline advanced stage Hodgkin lymphoma (HL) and frontline peripheral T-cell lymphoma (PTCL), and in other indications. Actual results or developments may differ materially from those projected or implied in these forward-looking statements due to factors such as unexpected adverse events, adverse regulatory actions, the degree of utilization and adoption of an approved treatment regimen by prescribing physicians, the difficulty and uncertainty of pharmaceutical product development, negative or disappointing clinical trial results and risks related to the duration and severity of the COVID-19 pandemic. 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 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 September 30, 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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  19. Seagen Inc. (NASDAQ:SGEN) announced today that it will host a virtual R&D day for investors and analysts on Monday, November 16, 2020 beginning at 10:00 a.m. Eastern Time. The program will include a presentation by members of Seagen leadership on the broad clinical development of the Company's marketed products, ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib), and its deep pipeline of innovative therapies for cancer.

    Access to the event will be available at the Company's website www.seagen.com in the Investors section. A replay will be archived on the Company's website following the live presentation.

    About Seagen

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

    Seagen Inc. (NASDAQ:SGEN) announced today that it will host a virtual R&D day for investors and analysts on Monday, November 16, 2020 beginning at 10:00 a.m. Eastern Time. The program will include a presentation by members of Seagen leadership on the broad clinical development of the Company's marketed products, ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib), and its deep pipeline of innovative therapies for cancer.

    Access to the event will be available at the Company's website www.seagen.com in the Investors section. A replay will be archived on the Company's website following the live presentation.

    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.

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  20. -Net Product Sales $267.5 Million in 3Q20, an Increase of 60 Percent Over 3Q19-

    -Collaborations with Merck for Ladiratuzumab Vedotin and TUKYSA; Seagen Received $725M in Upfront Payments and $1B Equity Investment-

    -Positive Data from Two PADCEV Clinical Trials to Support Global Registration Applications and Expand U.S. Indication-

    -Positive Data from Tisotumab Vedotin Pivotal Trial; BLA Planned to Support U.S. Accelerated Approval-

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

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the third quarter and nine months ended September 30, 2020. The Company also highlighted ADCETRIS® (brentuximab vedotin), PADCEV® (enfortumab vedotin-ejfv) and TUKYSA® (tucatinib) commercial and development…

    -Net Product Sales $267.5 Million in 3Q20, an Increase of 60 Percent Over 3Q19-

    -Collaborations with Merck for Ladiratuzumab Vedotin and TUKYSA; Seagen Received $725M in Upfront Payments and $1B Equity Investment-

    -Positive Data from Two PADCEV Clinical Trials to Support Global Registration Applications and Expand U.S. Indication-

    -Positive Data from Tisotumab Vedotin Pivotal Trial; BLA Planned to Support U.S. Accelerated Approval-

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

    Seagen Inc. (NASDAQ:SGEN) today reported financial results for the third quarter and nine months ended September 30, 2020. 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.

    "Our third quarter and year-to-date strong financial performance was driven by product sales across our diverse portfolio of three marketed products as well as the positive financial impact of our recent collaborations with Merck on ladiratuzumab vedotin and TUKYSA," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seagen. "We plan to report clinical and preclinical data across our programs at several medical meetings during the remainder of 2020. In addition, we are pursuing multiple regulatory submissions, including our TUKYSA MAA that is under review by the EMA, a planned tisotumab vedotin BLA in the U.S. and global marketing applications for PADCEV. With our significant financial resources, robust drug development pipeline, expanding footprint in Europe and strategic oncology collaborations, we are well-positioned to continue building Seagen to address the unmet medical needs of cancer patients around the globe."

    COMMERCIAL PRODUCTS HIGHLIGHTS

    ADCETRIS

    • Presenting Data in Multiple Abstracts at ASH: ADCETRIS will be featured in multiple abstracts at the 62nd Annual Meeting of the American Society of Hematology (ASH), which will be a virtual event taking place December 5-8, 2020. Data will include five-year follow-up results from the ECHELON-1 trial in frontline stage III and IV Hodgkin lymphoma and the ECHELON-2 trial in frontline CD30-expressing peripheral T-cell lymphomas.

    PADCEV

    • Announced Positive Topline Results from EV-301 Phase 3 Trial: In September 2020, Seagen and Astellas announced that PADCEV alone improved overall survival compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The trial was stopped early due to efficacy at the planned interim analysis. Data from EV-301 will be submitted for presentation at an upcoming scientific congress. In addition, the results will be submitted to the U.S. Food and Drug Administration (FDA) as the confirmatory trial following PADCEV's accelerated approval in 2019, and EV-301 is also intended to support global registrations.
    • Announced Positive Topline Results from Second Cohort in EV-201 Phase 2 Pivotal Trial: In October 2020, Seagen and Astellas reported durable objective responses in patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor, have not received a platinum-containing chemotherapy and are ineligible for cisplatin. Data from this second cohort of the EV-201 trial will be submitted for presentation at an upcoming scientific congress and may support a supplemental Biologics License Application (BLA) to extend use of PADCEV in the U.S.
    • Entered Into Additional Clinical Trial Collaboration with Merck: In October 2020, Seagen, Astellas and Merck entered into a clinical trial collaboration and supply agreement under which PADCEV and KEYTRUDA will be evaluated in a planned phase 3 trial to be conducted by Merck in cisplatin-eligible muscle invasive bladder cancer to complement the ongoing study in cis-ineligible patients in the same setting.

    TUKYSA

    • Received Approval in Fifth Country Under the FDA's Project Orbis Initiative: In August 2020, Seagen announced TUKYSA's approval in Australia for patients with metastatic HER2-positive breast cancer, including patients with brain metastases. Australia joined the U.S., Switzerland, Canada and Singapore in approving TUKYSA under Project Orbis, an initiative of the FDA Oncology Center of Excellence. In April 2020, TUKYSA became the first new medicine approved in the U.S. under Project Orbis. A TUKYSA marketing authorization application (MAA) is currently under review by the European Medicines Agency (EMA).
    • Entered into Exclusive License and Co-Development Agreement with Merck for TUKYSA: In September 2020, Seagen granted Merck an exclusive license to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. The collaboration is intended to accelerate global availability of TUKYSA. Seagen received an upfront payment of $125 million and is eligible for progress-dependent milestones of up to $65 million as well as tiered royalties on sales of TUKYSA in Merck's territory.
    • Expanded Clinical Development Program in HER2-Positive Cancers: Seagen initiated multiple trials to broadly evaluate TUKYSA in combination with other agents, including in gastrointestinal and other solid tumors.

    PIPELINE HIGHLIGHTS

    • Entered into a Global Co-Development and Co-Commercialization Agreement with Merck for Seagen's Ladiratuzumab Vedotin (LV): In September 2020, Seagen and Merck entered into an agreement under which the companies will jointly develop and equally share future costs and profits worldwide for LV, Seagen's investigational antibody-drug conjugate (ADC). Merck made an upfront payment to Seagen of $600 million. In October 2020, following expiration of the waiting period under the Hart-Scott-Rodino Act, Merck made a $1.0 billion equity investment in 5.0 million shares of Seagen at $200 per share. In addition, Seagen is eligible for progress-dependent milestone payments of up to $2.6 billion.
    • Presented Results from Tisotumab Vedotin (TV) Pivotal Trial at ESMO: In September 2020, Seagen and Genmab presented positive results at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 from the phase 2 single-arm clinical trial known as innovaTV 204. The trial is evaluating TV for the treatment of patients who have relapsed or progressed on or after prior treatment for recurrent or metastatic cervical cancer. The companies plan to submit a BLA to the FDA, which could support accelerated approval in the U.S.
    • Presenting Multiple Preclinical Abstracts at SITC: Several Seagen programs will be featured in presentations at the Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting 2020, taking place virtually November 9-14, 2020. Abstracts encompass preclinical findings on the ADCs ADCETRIS, TV and LV, as well as the Company's novel empowered antibody programs SEA-TGT and SEA-CD40.

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

    OTHER CORPORATE HIGHLIGHTS

    • Received Milestone Payments Under ADC Collaboration with GlaxoSmithKline (GSK): In August 2020, Seagen achieved two milestones totaling $26 million under its ADC collaboration with GSK, triggered by FDA and EMA approval of BlenrepTM (belantamab mafodotin) for multiple myeloma.
    • Announced Seagen R&D Day to be Held on November 16: The R&D day will highlight the broad clinical development of Seagen's marketed products as well as provide an overview of its deep pipeline of innovative cancer therapies.

    THIRD QUARTER AND NINE-MONTHS 2020 FINANCIAL RESULTS

    Revenues: Total revenues for the third quarter and nine months ended September 30, 2020 increased to $1.1 billion and $1.6 billion, respectively, compared to $213.3 million and $626.9 million for the same periods in 2019. Growth over 2019 was driven by the addition of PADCEV and TUKYSA to the Company's commercial portfolio and impact of the Company's recent collaborations with Merck. Revenues are composed of the following three components:

    • Net Product Sales:

     

    Three months ended September 30,

     

    Nine months ended September 30,

    (dollars in millions)

    2020

     

    2019

    % Change

     

    2020

     

    2019

    % Change

    Total Net Product Sales

    $

    267.5

     

     

    $

    167.6

     

    60

    %

     

    $

    706.5

     

     

    $

    461.6

     

    53

    %

    ADCETRIS

    163.3

     

     

    167.6

     

    (3

    )%

     

    494.9

     

     

    461.6

     

    7

    %

    PADCEV

    61.8

     

     

    N/A

     

     

    153.5

     

     

    N/A

     

    TUKYSA

    42.4

     

     

    N/A

     

     

    58.1

     

     

    N/A

     

    • Royalty Revenues: Royalty revenues for the third quarter and year-to-date in 2020 were $35.9 million and $87.5 million, respectively, compared to $27.3 million and $66.2 million for the same periods in 2019. Royalty revenues are primarily driven by sales of ADCETRIS outside the U.S. and Canada by Takeda. To a lesser extent, royalty revenues include sales of Polivy® (polatuzumab vedotin) by Roche, which is an ADC that uses Seagen technology.
    • Collaboration and License Agreement Revenues: Amounts earned under the Company's product, development and technology collaborations were $758.3 million and $780.3 million in the third quarter and year-to-date in 2020, respectively, compared to $18.4 million and $99.1 million for the same periods in 2019. The 2020 periods included $725 million in upfront license revenue related to the Merck collaborations for LV and TUKYSA that were entered into in September 2020. In addition, during the third quarter of 2020 Seagen received $26 million in total milestone payments from GSK, triggered by FDA and EMA approvals of Blenrep.

    Research and Development (R&D) Expenses: R&D expenses for the third quarter and year-to-date in 2020 were $217.7 million and $610.9 million, respectively, compared to $196.1 million and $518.3 million for the same periods in 2019. The increases in 2020 primarily reflect continued investment in the Company's pipeline.

    Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the third quarter and year-to-date in 2020 were $127.6 million and $375.5 million, respectively, compared to $96.1 million and $258.7 million for the same periods in 2019. The increases were primarily attributed to increased field sales personnel in the U.S. for Seagen's recently commercialized products, PADCEV and TUKYSA, as well as higher infrastructure costs to support the Company's continued growth and international expansion.

    Cost of Sales: Cost of sales for the third quarter and year-to-date in 2020 were $78.3 million and $156.0 million, respectively, compared to $10.8 million and $32.0 million for the same periods in 2019. The increases in 2020 were primarily due to the gross profit share with Astellas based on PADCEV sales, which were $29.1 million and $72.6 million in the third quarter and year-to-date, respectively. Cost of sales also increased in 2020 due a payment owed to a third-party technology licensor related to the TUKYSA license agreement with Merck, 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.

    Non-cash, share-based compensation cost for the first nine months of 2020 was $107.5 million, compared to $79.7 million for the same period in 2019.

    Net Income (Loss): Net income for the third quarter of 2020 was $636.2 million, or $3.50 per diluted share, compared to net loss of $91.9 million, or $0.55 per diluted share, for the third quarter of 2019. Net income for the nine months ended September 30, 2020 was $446.6 million, or $2.47 per diluted share, compared to net loss of $184.5 million, or $1.13 per diluted share, for the same period in 2019. Net income for the periods in 2020 is the result of the upfront license payments received from Merck. This includes an income tax provision of $3.2 million in the third quarter of 2020. Seagen utilized federal net operating loss carryforwards as allowed, however the Company incurred income taxes in some states that did not have deferred tax assets available.

    Cash and Investments: As of September 30, 2020, Seagen had $1.7 billion in cash and investments. The $1.0 billion equity investment by Merck, which closed in October 2020, will be reflected in the Company's December 31, 2020 cash and investments.

    2020 FINANCIAL OUTLOOK

    Seagen's 2020 financial guidance is shown below, which includes the impact of the Company's collaborations with Merck.

     

    Current

    Previous

    Revenues

    ADCETRIS net product sales

    $650 million to $660 million

    $675 million to $700 million

    PADCEV net product sales

    $215 million to $235 million

    Unchanged

    Royalty revenues

    $125 million to $130 million

    $105 million to $115 million

    Collaboration and license agreement revenues

    $1.03 billion to $1.04 billion

    $30 million to $50 million

    Operating expenses and other costs

    R&D expenses

    $820 million to $870 million

    Unchanged

    SG&A expenses

    $475 million to $525 million

    Unchanged

    Cost of Sales

    $205 million to $225 million

    $185 million to $205 million

    Non-cash costs1 (primarily attributable to

    share-based compensation)

    $180 million to $200 million

    Unchanged

    1. Non-cash costs 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 third quarter 2020 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 and supporting slides 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 10148256. 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 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, 2020 filed with the Securities and Exchange Commission (SEC), and the Company's subsequent periodic and current reports 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 applicable law.

    Seagen Inc.

    Condensed Consolidated Statements of Operations

    (Unaudited)

    (In thousands, except per share amounts)

     

    Three Months Ended September 30,

     

    Nine Months Ended September 30,

     

    2020

     

    2019

     

    2020

     

    2019

    Revenues:

     

     

     

     

     

     

     

    Net product sales

    $

    267,494

     

     

    $

    167,582

     

     

    $

    706,473

     

     

    $

    461,563

     

    Royalty revenues

    35,924

     

     

    27,261

     

     

    87,520

     

     

    66,218

     

    Collaboration and license agreement revenues

    758,313

     

     

    18,420

     

     

    780,250

     

     

    99,128

     

    Total revenues

    1,061,731

     

     

    213,263

     

     

    1,574,243

     

     

    626,909

     

    Costs and expenses:

     

     

     

     

     

     

     

    Cost of sales

    78,296

     

     

    10,827

     

     

    155,962

     

     

    32,024

     

    Research and development

    217,670

     

     

    196,119

     

     

    610,945

     

     

    518,313

     

    Selling, general and administrative

    127,579

     

     

    96,101

     

     

    375,470

     

     

    258,703

     

    Total costs and expenses

    423,545

     

     

    303,047

     

     

    1,142,377

     

     

    809,040

     

    Income (loss) from operations

    638,186

     

     

    (89,784)

     

     

    431,866

     

     

    (182,131)

     

    Investment and other income (loss), net

    1,223

     

     

    (2,129)

     

     

    17,951

     

     

    (2,349)

     

    Income (loss) before income taxes

    639,409

     

     

    (91,913)

     

     

    449,817

     

     

    (184,480)

     

    Provision for income taxes

    (3,242)

     

     

     

     

    (3,242)

     

     

     

    Net income (loss)

    $

    636,167

     

     

    $

    (91,913)

     

     

    $

    446,575

     

     

    $

    (184,480)

     

    Net income (loss) per share - basic

    $

    3.65

     

     

    $

    (0.55)

     

     

    $

    2.58

     

     

    $

    (1.13)

     

    Net income (loss) per share - diluted

    $

    3.50

     

     

    $

    (0.55)

     

     

    $

    2.47

     

     

    $

    (1.13)

     

    Shares used in computation of per share amounts - basic

    174,460

     

     

    168,109

     

     

    173,409

     

     

    163,428

     

    Shares used in computation of per share amounts - diluted

    181,877

     

     

    168,109

     

     

    180,939

     

     

    163,428

     

    Seagen Inc.

    Condensed Consolidated Balance Sheets

    (Unaudited)

    (In thousands)

     

    September 30, 2020

     

    December 31, 2019

    Assets

     

     

     

    Cash, cash equivalents and investments

    $

    1,718,375

     

     

    $

    868,338

     

    Other assets

    1,286,586

     

     

    1,337,528

     

    Total assets

    $

    3,004,961

     

     

    $

    2,205,866

     

    Liabilities and Stockholders' Equity

     

     

     

    Accounts payable and accrued liabilities

    $

    342,688

     

     

    $

    259,357

     

    Deferred revenue

    250,450

     

     

     

    Long-term liabilities

    153,793

     

     

    70,222

     

    Stockholders' equity

    2,258,030

     

     

    1,876,287

     

    Total liabilities and stockholders' equity

    $

    3,004,961

     

     

    $

    2,205,866

     

     

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  21. -Merck's Equity Stake in Seagen in Connection with Agreement to Co-Develop and Commercialize Ladiratuzumab Vedotin-

    Seagen Inc. (NASDAQ:SGEN) today announced the closing of a $1.0 billion equity investment by Merck in 5.0 million newly-issued shares of Seagen common stock at a price of $200 per share. The closing occurred following expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act). The investment was made in connection with a global collaboration with Merck to co-develop and commercialize ladiratuzumab vedotin, an investigational antibody-drug conjugate (ADC) targeting LIV-1, which is currently in clinical trials for breast cancer and other solid tumors.

    "This investment by Merck further…

    -Merck's Equity Stake in Seagen in Connection with Agreement to Co-Develop and Commercialize Ladiratuzumab Vedotin-

    Seagen Inc. (NASDAQ:SGEN) today announced the closing of a $1.0 billion equity investment by Merck in 5.0 million newly-issued shares of Seagen common stock at a price of $200 per share. The closing occurred following expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act). The investment was made in connection with a global collaboration with Merck to co-develop and commercialize ladiratuzumab vedotin, an investigational antibody-drug conjugate (ADC) targeting LIV-1, which is currently in clinical trials for breast cancer and other solid tumors.

    "This investment by Merck further strengthens our balance sheet, and provides us with considerable financial resources to continue building Seagen as a global, multi-product oncology company," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seagen. "We are investing in broad clinical development of our approved products, advancing our late-stage programs and conducting R&D to ensure a robust early-stage pipeline of innovative therapies for the treatment of cancer."

    The financial impact of the collaboration, including the stock purchase agreement, will be discussed during Seagen's third quarter financial results conference call on October 29, 2020.

    Ladiratuzumab Vedotin Collaboration Details

    Under the terms of the agreement, Seagen and Merck will collaborate and equally share costs on the global development of ladiratuzumab vedotin and other LIV-1-targeting ADCs. The companies have agreed to jointly develop and share future costs and profits for ladiratuzumab vedotin on a 50:50 basis worldwide. Merck paid Seagen $600 million upfront and made a $1.0 billion equity investment in 5.0 million shares of Seagen common stock at a price of $200 per share in connection with entry into the agreement. In addition, Seagen will be eligible to receive up to $2.6 billion in milestone payments, including $850 million in development milestones and $1.75 billion in sales milestones.

    The companies will jointly develop and commercialize ladiratuzumab vedotin and equally share profits worldwide. The companies will co-commercialize in the U.S. and Europe. Seagen will be responsible for marketing applications for approval in the U.S. and Canada, and will record sales in the U.S., Canada and Europe. Merck will be responsible for marketing applications for approval in countries outside the U.S. and Canada, and for sales efforts in countries outside the U.S., Europe and Canada. Including the upfront payment, equity investment proceeds and potential milestone payments, Seagen is eligible to receive up to $4.2 billion.

    About Ladiratuzumab Vedotin

    Ladiratuzumab vedotin is a novel investigational ADC targeted to LIV-1. Most metastatic breast cancers express LIV-1, which also has been detected in several other cancers, including lung, head and neck, esophageal and gastric. Ladiratuzumab vedotin utilizes Seagen's proprietary ADC technology and consists of a LIV-1-targeted monoclonal antibody linked to a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE) by a protease-cleavable linker. This novel ADC is designed to bind to LIV-1 on cancer cells and release the cell-killing agent into target cells upon internalization. Ladiratuzumab vedotin may also cause antitumor activity through other mechanisms, including activation of an immune response by induction of immunogenic cell death.

    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. Our U.S. headquarters are in the Seattle, Washington area, with 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 @Seagen on Twitter.

    Forward Looking Statements

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to Seagen's potential receipt of milestone payments, including development- and sales-based milestone payments, under the ladiratuzumab vedotin collaboration with Merck (the Collaboration Agreement); anticipated activities of the parties under the Collaboration Agreement; Seagen's expectation of investing in clinical trials aimed at maximizing the potential of its commercial products, expanding globally and advancing its deep pipeline of innovative therapies for the treatment of cancer; and any 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, risks and uncertainties related to: Seagen's ability to maintain the Collaboration Agreement, including the risk that if Merck were to breach or terminate the Collaboration Agreement, Seagen would not obtain all of the anticipated financial and other benefits of the Collaboration Agreement, and the development and/or commercialization of ladiratuzumab vedotin could be delayed, perhaps substantially; delays, setbacks or failures in clinical development activities for a variety of reasons, including 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; the risk that the parties may not be successful in their joint development efforts under the Collaboration Agreement and that, even if successful, the parties may be unable to successfully launch and commercialize ladiratuzumab vedotin; and 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 Seagen's Quarterly Report on Form 10-Q for the quarter ended June 30, 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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  22. Seagen Inc. (NASDAQ:SGEN) announced today that it will report its third quarter 2020 financial results on Thursday, October 29, 2020 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 general corporate update. Access to the event can be obtained as follows:

    Thursday, October 29, 2020
    1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time

    • Telephone 844-763-8274 (domestic) or +1 412-717-9224 (international); conference ID 10148256
    • 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 Inc. is a global biotechnology company that…

    Seagen Inc. (NASDAQ:SGEN) announced today that it will report its third quarter 2020 financial results on Thursday, October 29, 2020 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 general corporate update. Access to the event can be obtained as follows:

    Thursday, October 29, 2020

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

    • Telephone 844-763-8274 (domestic) or +1 412-717-9224 (international); conference ID 10148256
    • 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 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.

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  23. - Durable Responses Observed in Patients Who Had Previously Received Immunotherapy but Were Ineligible for Cisplatin in Locally Advanced or Metastatic Setting -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced positive topline results from the second cohort of patients in the pivotal phase 2 single-arm clinical trial known as EV-201. The cohort is evaluating the antibody-drug conjugate PADCEV® (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and have not received a platinum-containing chemotherapy and are ineligible for cisplatin. Results showed a 52 percent…

    - Durable Responses Observed in Patients Who Had Previously Received Immunotherapy but Were Ineligible for Cisplatin in Locally Advanced or Metastatic Setting -

    Seagen Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced positive topline results from the second cohort of patients in the pivotal phase 2 single-arm clinical trial known as EV-201. The cohort is evaluating the antibody-drug conjugate PADCEV® (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and have not received a platinum-containing chemotherapy and are ineligible for cisplatin. Results showed a 52 percent objective response rate (ORR) [95% Confidence Interval (CI): 40.8, 62.4] per blinded independent central review and a median duration of response of 10.9 months. The most frequently reported treatment-related adverse events Grade 3 or greater that occurred in more than 5 percent of patients were: neutropenia, rash, fatigue, increased lipase, diarrhea, decreased appetite, anemia and hyperglycemia. Data from cohort 2 of the trial will be submitted for presentation at an upcoming scientific congress and will be discussed with regulatory authorities.

    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.1, 2 The U.S. Food and Drug Administration (FDA) granted accelerated approval to PADCEV in 2019 based on results from the first cohort in this trial, which included patients whose disease had progressed during or following platinum-based chemotherapy and a PD-1/L1 inhibitor.

    "Advanced urothelial cancer in patients who have received immunotherapy and are ineligible for cisplatin is a particularly difficult disease to treat," 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. "Typically, these patients are frail, suffer from multiple comorbidities beyond their urothelial cancer and are not able to tolerate additional treatment beyond immunotherapy, leading many to discontinue therapy altogether."

    "This is the first trial to report objective responses in patients with advanced urothelial cancer who had previously received immunotherapy but were ineligible for cisplatin in this setting due to inadequate kidney function or other conditions," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "These promising new data from EV-201 may support a regulatory application to extend use of PADCEV in U.S. patients whose cancer has progressed after immunotherapy and who are ineligible for cisplatin."

    "We are committed to developing new treatments for patients with hard-to-treat cancers, such as those with locally advanced or metastatic urothelial cancer that has progressed following treatment with a PD-1 or PD-L1 inhibitor and who are ineligible for cisplatin therapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "We look forward to discussing these data with regulatory authorities including the FDA."

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the urothelial cells that line the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.3 Globally, approximately 580,000 people will be diagnosed with bladder cancer in 2020, and bladder cancer will be attributed to approximately 210,000 deaths worldwide.4

    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.5 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.

    For more information about the EV-201 clinical trial, please visit clinicaltrials.gov.

    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.1

    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.1,2 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).2 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 PADCEV (enfortumab vedotin-ejfv) 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 the potential submission of a regulatory application to extend the use of PADCEV in U.S. patients or plans to discuss data from cohort 2 of the EV-201 trial with regulatory 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 that the data from cohort 2 of the EV-201 trial may not be selected for presentation at scientific congresses; the possibility of delays in the submission of any regulatory application to extend the use of PADCEV in U.S. patients; that the results from cohort 2 of the EV-201 trial may not be enough to support any approvals by regulatory authorities; that any product labeling that is approved may be narrower or less desirable than anticipated; the risk of adverse events or safety signals; and the possibility 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, 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.

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

    2 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.

    3 American Society of Clinical Oncology. Bladder Cancer: Introduction (10-2017). https://www.cancer.net/cancertypes/bladder-cancer/introduction. Accessed 05-09-2019.

    4 International Agency for Research on Cancer. Cancer Tomorrow: Bladder. http://gco.iarc.fr/tomorrow. Accessed 07-31-2020.

    5 ClinicalTrials.gov Identifier: NCT03219333. A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201). https://clinicaltrials.gov/ct2/show/NCT03219333. Accessed on 08-03-2020.

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  24. TOKYO and BOTHELL, Wash., Oct. 12, 2020 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced positive topline results from the second cohort of patients in the pivotal phase 2 single-arm clinical trial known as EV-201. The cohort is evaluating the antibody-drug conjugate PADCEV® (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and have not received a platinum-containing chemotherapy and are ineligible for cisplatin. Results showed a 52 percent objective response rate (ORR) [95% Confidence Interval (CI): 40.8, 62.4] per blinded independent central…

    TOKYO and BOTHELL, Wash., Oct. 12, 2020 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO:  Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (NASDAQ:SGEN) today announced positive topline results from the second cohort of patients in the pivotal phase 2 single-arm clinical trial known as EV-201. The cohort is evaluating the antibody-drug conjugate PADCEV® (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and have not received a platinum-containing chemotherapy and are ineligible for cisplatin. Results showed a 52 percent objective response rate (ORR) [95% Confidence Interval (CI): 40.8, 62.4] per blinded independent central review and a median duration of response of 10.9 months. The most frequently reported treatment-related adverse events Grade 3 or greater that occurred in more than 5 percent of patients were: neutropenia, rash, fatigue, increased lipase, diarrhea, decreased appetite, anemia and hyperglycemia. Data from cohort 2 of the trial will be submitted for presentation at an upcoming scientific congress and will be discussed with regulatory authorities.

    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.1,2 The U.S. Food and Drug Administration (FDA) granted accelerated approval to PADCEV in 2019 based on results from the first cohort in this trial, which included patients whose disease had progressed during or following platinum-based chemotherapy and a PD-1/L1 inhibitor.

    "Advanced urothelial cancer in patients who have received immunotherapy and are ineligible for cisplatin is a particularly difficult disease to treat," 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. "Typically, these patients are frail, suffer from multiple comorbidities beyond their urothelial cancer and are not able to tolerate additional treatment beyond immunotherapy, leading many to discontinue therapy altogether."

    "We are committed to developing new treatments for patients with hard-to-treat cancers, such as those with locally advanced or metastatic urothelial cancer that has progressed following treatment with a PD-1 or PD-L1 inhibitor and who are ineligible for cisplatin therapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "We look forward to discussing these data with regulatory authorities including the FDA."

    "This is the first trial to report objective responses in patients with advanced urothelial cancer who had previously received immunotherapy but were ineligible for cisplatin in this setting due to inadequate kidney function or other conditions," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "These promising new data from EV-201 may support a regulatory application to extend use of PADCEV in U.S. patients whose cancer has progressed after immunotherapy and who are ineligible for cisplatin."

    Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the urothelial cells that line the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.3 Globally, approximately 580,000 people will be diagnosed with bladder cancer in 2020, and bladder cancer will be attributed to approximately 210,000 deaths worldwide.4

    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.5 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.

    For more information about the EV-201 clinical trial, please visit clinicaltrials.gov.

    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.1

    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.1,2 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).2 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 PADCEV (enfortumab vedotin-ejfv) 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 cohort 2 of the EV-201 trial for presentation at an upcoming scientific congress; intended regulatory actions, including the potential submission of a regulatory application to extend the use of PADCEV in U.S. patients or plans to discuss data from cohort 2 of the EV-201 trial with regulatory 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 that the data from cohort 2 of the EV-201 trial may not be selected for presentation at scientific congresses; the possibility of delays in the submission of any regulatory application to extend the use of PADCEV in U.S. patients; that the results from cohort 2 of the EV-201 trial may not be enough to support any approvals by regulatory authorities; that any product labeling that is approved may be narrower or less desirable than anticipated; the risk of adverse events or safety signals; and the possibility 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, 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.

    1PADCEV [package insert]. Northbrook, IL: Astellas, Inc.

    2Challita-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.

    3American Society of Clinical Oncology. Bladder cancer: introduction (10-2017). https://www.cancer.net/cancertypes/bladder-cancer/introduction. Accessed 05-09-2019.

    4International Agency for Research on Cancer. Cancer Tomorrow: Bladder. http://gco.iarc.fr/tomorrow. Accessed 07-31-2020.

    5ClinicalTrials.gov Identifier: NCT03219333. A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201). https://clinicaltrials.gov/ct2/show/NCT03219333. Accessed on 08-03-2020.

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/astellas-and-seagen-announce-positive-topline-results-from-second-cohort-of-patients-in-phase-2-pivotal-trial-of-padcev-enfortumab-vedotin-ejfv-in-advanced-urothelial-cancer-301149817.html

    SOURCE Astellas Pharma Inc.

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  25. - New Name Reflects Company's Expanding Global Presence and Therapeutic Portfolio -

    Seagen Inc. is the new corporate name for Seattle Genetics, Inc. (NASDAQ:SGEN), a global biotechnology company dedicated to developing innovative cancer medicines that make a meaningful difference in people's lives around the world. The evolution of the corporate name reflects the transformation of Seagen as it expands operations globally to bring its marketed medicines to more patients, pursues new indications for approved medicines and continues to advance its pipeline of novel therapies for solid tumors and blood-related cancers. The Company's common stock will continue to trade under its current ticker symbol: "SGEN."

    "The change in our corporate name…

    - New Name Reflects Company's Expanding Global Presence and Therapeutic Portfolio -

    Seagen Inc. is the new corporate name for Seattle Genetics, Inc. (NASDAQ:SGEN), a global biotechnology company dedicated to developing innovative cancer medicines that make a meaningful difference in people's lives around the world. The evolution of the corporate name reflects the transformation of Seagen as it expands operations globally to bring its marketed medicines to more patients, pursues new indications for approved medicines and continues to advance its pipeline of novel therapies for solid tumors and blood-related cancers. The Company's common stock will continue to trade under its current ticker symbol: "SGEN."

    "The change in our corporate name from Seattle Genetics to Seagen reflects who we are today, as we expand our presence beyond the Pacific Northwest and outside of the United States to support the commercialization of TUKYSA globally," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seagen. "We have three marketed products and a robust development pipeline of novel targeted product candidates. As we increase our global presence by adding new team members and locations outside of the United States as well as through strategic partnerships, we are better positioned to bring important new therapies to cancer patients around the world. Our passion for helping patients is stronger than ever."

    Seagen is focused on discovering safe and effective novel therapeutics to advance cancer care. As a pioneer in antibody-drug conjugates (ADCs), Seagen has been a leader in novel cancer therapeutics for more than 20 years. ADCETRIS® (brentuximab vedotin) is approved in over 70 countries around the world and continues to make a difference in the lives of patients with several types of lymphomas. In the last year, Seagen successfully launched two new cancer medicines that address significant unmet medical needs. PADCEV® (enfortumab vedotin) was the first antibody-drug conjugate (ADC) approved for locally advanced or metastatic urothelial (bladder) cancer following treatment with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. TUKYSA® (tucatinib) was approved in the U.S. for metastatic HER2-positive breast cancer following an expedited U.S. Food and Drug Administration (FDA) approval. TUKYSA has also received approval in Australia, Canada, Singapore and Switzerland under the Project Orbis initiative of the FDA Oncology Center of Excellence and is under review with the European Medicines Agency (EMA).

    The company also recently entered into two strategic collaborations with Merck that will accelerate and broaden the global development of the investigational ADC ladiratuzumab vedotin and the commercialization of TUKYSA in Asia, the Middle East, Latin America and other regions outside of the U.S., Canada and Europe. These strategic collaborations will further expand Seagen's global presence in oncology and ability to deliver cancer medicines around the world.

    Along with the new name, the company will adopt a new logo and will change its corporate website from www.seattlegenetics.com to www.seagen.com. Seagen will provide further updates to customers, suppliers and partners regarding these changes in the implementation of the new name.

    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 pipeline, its ability to develop and commercialize innovative cancer medicines, its ability to expand its operations globally and bring TUKYSA and other potential new therapies to patients around the world, including in collaboration with Merck. 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; inability to show sufficient activity in clinical trials; the possibility of adverse regulatory actions; the possibility that the Company may encounter challenges in commercializing its therapeutic agents outside of the United States, including with respect to regulatory, reimbursement, compliance, operational or other matters; the possibility that the Company may encounter challenges in its collaborations with Merck or other collaborators which may delay or limit its ability to deliver its current and future potential therapeutic agents globally; and 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 June 30, 2020 filed with the Securities and Exchange Commission. The Company 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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  26. Media Release


    COPENHAGEN, Denmark and BOTHELL, Wash., 21 September 2020

    • Data featured in late-breaking proffered paper oral presentation
       
    • Biologics license application submission planned to support accelerated approval pathway with the FDA


    Genmab A/S (NASDAQ:GMAB) and Seattle Genetics, Inc. (NASDAQ:SGEN) today presented data from the innovaTV 204 pivotal phase 2, single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent and/or metastatic cervical cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
    Patients had previously received a doublet chemotherapy and, if eligible, bevacizumab as first-line therapy. Results from the trial showed a 24 percent confirmed…

    Media Release





    COPENHAGEN, Denmark and BOTHELL, Wash., 21 September 2020

    • Data featured in late-breaking proffered paper oral presentation

       
    • Biologics license application submission planned to support accelerated approval pathway with the FDA



    Genmab A/S (NASDAQ:GMAB) and Seattle Genetics, Inc. (NASDAQ:SGEN) today presented data from the innovaTV 204 pivotal phase 2, single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent and/or metastatic cervical cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
    Patients had previously received a doublet chemotherapy and, if eligible, bevacizumab as first-line therapy. Results from the trial showed a 24 percent confirmed objective response rate (ORR) by independent central review with a median duration of response (DOR) of 8.3 months. The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia, epistaxis (nose bleeds), nausea, conjunctivitis, fatigue and dry eye. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor (TF), which is prevalent on solid tumors including cervical cancer and can promote tumor growth, angiogenesis and metastasis.1  

    Current therapies for previously treated recurrent and/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.1-8

    "Following resistance to or progression on first-line standard of care therapy, there are limited treatment options for women with metastatic cervical cancer," said Robert L. Coleman, M.D., Chief Scientific Officer for US Oncology Research and lead investigator of the innovaTV 204 clinical trial. "The current treatment approaches for this disease setting have low objective response rates with poor outcomes. The results of the tisotumab vedotin phase 2 clinical trial are encouraging as they demonstrate clinically meaningful, durable responses with a manageable side effect profile."

    "We are encouraged by the innovaTV 204 trial results, which suggests that tisotumab vedotin as a monotherapy could potentially become an important option for women with metastatic and or recurrent cervical cancer," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Seattle Genetics and Genmab are committed to making a difference in the lives of cancer patients and we look forward to working with the FDA with a goal to make this potential treatment option available to women as quickly as possible."

    "Tisotumab vedotin has demonstrated meaningful clinical activity in patients with recurrent and/or metastatic cervical cancer for whom there is a high unmet need for new therapies," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "Based on these results, we look forward to submitting a Biologics License Application to the FDA under the accelerated approval pathway."

    Data presented at ESMO include the primary endpoint of confirmed ORR as assessed by independent central review in 101 patients treated with tisotumab vedotin in the trial. Secondary endpoints included DOR, time to response, progression-free survival (PFS), overall survival (OS), safety and tolerability.

    Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer: Results from the Phase 2 innovaTV 204/GOG-3023/ENGOT-cx6 Study (Abstract #3435, late-breaking proffered paper oral presentation at 17:04 CET on Monday, September 21, 2020)

    Efficacy:

    • The primary endpoint of ORR (complete response + partial response) showed a 24 percent confirmed ORR [95% Confidence Interval (CI): 15.9%-33.3%], including 7 patients (7 percent) with a complete response and 17 patients (17 percent) with a partial response.
      • After a median follow-up of 10 months, the median DOR was 8.3 months (95% CI: 4.2, not reached).
    • The median time to response was 1.4 months (range, 1.1-5.1), with activity generally observed within the first two treatment cycles.
    • Subgroup analyses demonstrated that responses were generally consistent across subgroups regardless of tumor histology, lines of prior therapy, responses to prior systemic regimen, and doublet chemotherapy with bevacizumab as first-line treatment.
    • The median PFS was 4.2 months (95% CI: 3.0, 4.4) and the six-month PFS rate was 30 percent (95% CI: 20.8, 40.1).
    • The median OS was 12.1 months (95% CI: 9.6, 13.9) and the six-month OS rate was 79 percent (95% CI: 69.3, 85.6).

    Safety:

    • The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia (Grade 1/2 at 38 percent), epistaxis (nose bleeds, Grade 1/2 at 30 percent), nausea (Grade 1/2 at 27 percent), conjunctivitis (Grade 1/2 at 26 percent), fatigue (Grade 1/2 at 24 percent, Grade 3 or higher at 2 percent) and dry eye (Grade 1/2 at 23 percent). Most treatment-related adverse events were Grade 1 or 2 and no new safety signals were reported. One death due to septic shock was considered by the investigator to be related to therapy.
    • Pre-specified adverse events of interest with tisotumab vedotin treatment included ocular events, bleeding and peripheral neuropathy. Ocular adverse events considered to be related to therapy that occurred in patients were mostly mild to moderate (Grade 1 at 25 percent, Grade 2 at 27 percent, Grade 3 at 2 percent) of which a majority of the events resolved (86 percent) and were managed with an eye care plan. Bleeding events considered to be related to therapy that occurred in patients were mostly mild (Grade 1 at 34 percent, Grade 2 at 3 percent, Grade 3 at 2 percent) of which a majority of the events resolved (90 percent). The most common bleeding events included Grade 1 epistaxis (28 percent). Peripheral neuropathy events considered to be related to therapy were mostly mild to moderate (Grade 1 at 17 percent, Grade 2 at 9 percent, Grade 3 at 7 percent) and managed with dose modifications. Resolution of peripheral neuropathy was limited by follow-up period.

    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.9 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.10 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.

    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 and/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 in collaboration with European Network of Gynaecological Oncological Trial Groups (ENGOT) and Gynecologic Oncology Group (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 Tisotumab Vedotin



    Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab's fully human monoclonal antibody specific for tissue factor and Seattle Genetics' 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 protein that can promote tumor growth, angiogenesis and metastasis.1 Based on its high expression on many 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 Seattle Genetics, 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 ongoing clinical trials as monotherapy in a range of solid tumors, including recurrent and/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.

    About Genmab

    Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. Founded in 1999, the company is the creator of the following approved antibodies: DARZALEX® (daratumumab, under agreement with Janssen Biotech, Inc.) for the treatment of certain multiple myeloma indications in territories including the U.S., Europe and Japan, Kesimpta® (subcutaneous ofatumumab, under agreement with Novartis AG), for the treatment of adults with relapsing forms of multiple sclerosis in the U.S. and TEPEZZA® (teprotumumab, under agreement with Roche granting sublicense to Horizon Therapeutics plc) for the treatment of thyroid eye disease in the U.S. A subcutaneous formulation of daratumumab, known as DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) in the U.S., has been approved in the U.S. and Europe for the treatment of adult patients with certain multiple myeloma indications. The first approved Genmab created therapy, Arzerra® (ofatumumab, under agreement with Novartis AG), approved for the treatment of certain chronic lymphocytic leukemia indications, is available in Japan and is also available in other territories via compassionate use or oncology access programs. Daratumumab is in clinical development by Janssen for the treatment of additional multiple myeloma indications, other blood cancers and amyloidosis. Genmab also has a broad clinical and pre-clinical product pipeline. Genmab's technology base consists of validated and proprietary next generation antibody technologies - the DuoBody® platform for generation of bispecific antibodies, the HexaBody® platform, which creates effector function enhanced antibodies, the HexElect® platform, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing therapeutic potency and the DuoHexaBody® platform, which enhances the potential potency of bispecific antibodies through hexamerization. The company intends to leverage these technologies to create opportunities for full or co-ownership of future products. Genmab has alliances with top tier pharmaceutical and biotechnology companies. Genmab is headquartered in Copenhagen, Denmark with sites in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.

    About Seattle Genetics



    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. ADCETRIS® (brentuximab vedotin) and PADCEV® (enfortumab vedotin-ejfv) use the Company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSA® (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

    CONTACTS:

    Genmab A/S

    Media:

    Marisol Peron, Corporate Vice President, Communications & Investor Relations

    +1 609 524 0065

    Investors:

    Andrew Carlsen, Senior Director, Investor Relations

    +45 3377 9558

    Seattle Genetics

    Media:

    Monique Greer

    (425) 527-4641

    Investors:

    Peggy Pinkston

    (425) 527-4160

    Genmab Forward Looking Statement



    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®; HexElect®; and UniBody®. Arzerra® and Kesimpta® are trademarks of Novartis AG or its affiliates. DARZALEX® and DARZALEX FASPRO™ are trademarks of Janssen Pharmaceutica NV. TEPEZZA® is a trademark of Horizon Therapeutics plc.

    Seattle Genetics Forward Looking Statement



    Certain of the statements made in this press release are forward looking, such as those, among others, relating to plans to submit a Biologics License Application (BLA) to FDA under FDA's Accelerated Approval program based on the results of the innovaTV 204, 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 the possibility of delays in the submission of a BLA to the FDA, that the data from innovaTV 204 may not be sufficient to support accelerated approval of tisotumab vedotin, 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 Seattle Genetics is contained under the caption "Risk Factors" included in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 filed with the Securities and Exchange Commission. Seattle Genetics 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 Van de Berg YW et al. Blood 2012;119:924.

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

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

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

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

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

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

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

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

    10 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/.





    Media Release no. 12

    CVR no. 2102 3884

    LEI Code 529900MTJPDPE4MHJ122

    Genmab A/S

    Kalvebod Brygge 43

    1560 Copenhagen V

    Denmark

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  27. - Data Featured in Late-Breaking Proffered Paper Oral Presentation -

    - Biologics License Application Submission Planned to Support Accelerated Approval Pathway with the FDA -

    Seattle Genetics, Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today presented data from the innovaTV 204 pivotal phase 2, single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent and/or metastatic cervical cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. Patients had previously received a doublet chemotherapy and, if eligible, bevacizumab as first-line therapy. Results from the trial showed a 24 percent confirmed objective response rate (ORR) by independent central review…

    - Data Featured in Late-Breaking Proffered Paper Oral Presentation -

    - Biologics License Application Submission Planned to Support Accelerated Approval Pathway with the FDA -

    Seattle Genetics, Inc. (NASDAQ:SGEN) and Genmab A/S (NASDAQ:GMAB) today presented data from the innovaTV 204 pivotal phase 2, single-arm clinical trial evaluating tisotumab vedotin as monotherapy in patients with previously treated recurrent and/or metastatic cervical cancer at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. Patients had previously received a doublet chemotherapy and, if eligible, bevacizumab as first-line therapy. Results from the trial showed a 24 percent confirmed objective response rate (ORR) by independent central review with a median duration of response (DOR) of 8.3 months. The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia, epistaxis (nose bleeds), nausea, conjunctivitis, fatigue and dry eye. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor (TF), which is prevalent on solid tumors including cervical cancer and can promote tumor growth, angiogenesis and metastasis.1

    Current therapies for previously treated recurrent and/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.1-8

    "Following resistance to, or progression on first-line standard of care therapy, there are currently limited treatment options for women with metastatic cervical cancer," said Robert L. Coleman, M.D., Chief Scientific Officer for US Oncology Research and lead investigator of the innovaTV 204 clinical trial. "The current treatment approaches for this disease setting have low objective response rates with poor outcomes. The results of the tisotumab vedotin phase 2 clinical trial are encouraging as they demonstrate clinically meaningful, durable responses with a manageable side effect profile."

    "Tisotumab vedotin has demonstrated meaningful clinical activity in patients with recurrent and/or metastatic cervical cancer for whom there is a high unmet need for new therapies," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "Based on these results, we look forward to submitting a Biologics License Application to the FDA under the accelerated approval pathway."

    "We are encouraged by the innovaTV 204 trial results, which suggests that tisotumab vedotin as a monotherapy could potentially become an important option for women with metastatic and or recurrent cervical cancer," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Seattle Genetics and Genmab are committed to making a difference in the lives of cancer patients, and we look forward to working with the FDA with a goal to make this potential treatment option available to women as quickly as possible."

    Data presented at ESMO include the primary endpoint of confirmed ORR as assessed by independent central review in 101 patients treated with tisotumab vedotin in the trial. Secondary endpoints included DOR, time to response, progression-free survival (PFS), overall survival (OS), safety and tolerability.

    Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer: Results from the Phase 2 innovaTV 204/GOG-3023/ENGOT-cx6 Study (Abstract #3435, late-breaking proffered paper oral presentation at 17:04 CET on Monday, September 21, 2020)

    Efficacy:

    • The primary endpoint of ORR (complete response + partial response) showed a 24 percent confirmed ORR [95% Confidence Interval (CI): 15.9%-33.3%], including 7 patients (7 percent) with a complete response and 17 patients (17 percent) with a partial response.
      • After a median follow-up of 10 months, the median DOR was 8.3 months (95% CI: 4.2, not reached).
    • The median time to response was 1.4 months (range, 1.1-5.1), with activity generally observed within the first two treatment cycles.
    • Subgroup analyses demonstrated that responses were generally consistent across subgroups regardless of tumor histology, lines of prior therapy, responses to prior systemic regimen, and doublet chemotherapy with bevacizumab as first-line treatment.
    • The median PFS was 4.2 months (95% CI: 3.0, 4.4) and the six-month PFS rate was 30 percent (95% CI: 20.8, 40.1).
    • The median OS was 12.1 months (95% CI: 9.6, 13.9) and the six-month OS rate was 79 percent (95% CI: 69.3, 85.6).

    Safety:

    • The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia (Grade 1/2 at 38 percent), epistaxis (nose bleeds, Grade 1/2 at 30 percent), nausea (Grade 1/2 at 27 percent), conjunctivitis (Grade 1/2 at 26 percent), fatigue (Grade 1/2 at 24 percent, Grade 3 or higher at 2 percent) and dry eye (Grade 1/2 at 23 percent). Most treatment-related adverse events were Grade 1 or 2 and no new safety signals were reported. One death due to septic shock was considered by the investigator to be related to therapy.
    • Pre-specified adverse events of interest with tisotumab vedotin treatment included ocular events, bleeding and peripheral neuropathy. Ocular adverse events considered to be related to therapy that occurred in patients were mostly mild to moderate (Grade 1 at 25 percent, Grade 2 at 27 percent, Grade 3 at 2 percent) of which a majority of the events resolved (86 percent) and were managed with an eye care plan. Bleeding events considered to be related to therapy that occurred in patients were mostly mild (Grade 1 at 34 percent, Grade 2 at 3 percent, Grade 3 at 2 percent) of which a majority of the events resolved (90 percent). The most common bleeding events included Grade 1 epistaxis (28 percent). Peripheral neuropathy events considered to be related to therapy were mostly mild to moderate (Grade 1 at 17 percent, Grade 2 at 9 percent, Grade 3 at 7 percent) and managed with dose modifications. Resolution of peripheral neuropathy was limited by follow-up period.

    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.9 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.10 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.

    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 and/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 in collaboration with European Network of Gynaecological Oncological Trial Groups (ENGOT) and Gynecologic Oncology Group (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 Tisotumab Vedotin

    Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab's fully human monoclonal antibody specific for tissue factor and Seattle Genetics' 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 protein that can promote tumor growth, angiogenesis and metastasis.1 Based on its high expression on many 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 Seattle Genetics, 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 ongoing clinical trials as monotherapy in a range of solid tumors, including recurrent and/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.

    About Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. ADCETRIS® (brentuximab vedotin) and PADCEV® (enfortumab vedotin-ejfv) use the Company's industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSA® (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

    About Genmab

    Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. Founded in 1999, the company is the creator of the following approved antibodies: DARZALEX® (daratumumab, under agreement with Janssen Biotech, Inc.) for the treatment of certain multiple myeloma indications in territories including the U.S., Europe and Japan, Kesimpta® (subcutaneous ofatumumab, under agreement with Novartis AG), for the treatment of adults with relapsing forms of multiple sclerosis in the U.S. and TEPEZZA® (teprotumumab, under agreement with Roche granting sublicense to Horizon Therapeutics plc) for the treatment of thyroid eye disease in the U.S. A subcutaneous formulation of daratumumab, known as DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) in the U.S., has been approved in the U.S. and Europe for the treatment of adult patients with certain multiple myeloma indications. The first approved Genmab created therapy, Arzerra® (ofatumumab, under agreement with Novartis AG), approved for the treatment of certain chronic lymphocytic leukemia indications, is available in Japan and is also available in other territories via compassionate use or oncology access programs. Daratumumab is in clinical development by Janssen for the treatment of additional multiple myeloma indications, other blood cancers and amyloidosis. Genmab also has a broad clinical and pre-clinical product pipeline. Genmab's technology base consists of validated and proprietary next generation antibody technologies - the DuoBody® platform for generation of bispecific antibodies, the HexaBody® platform, which creates effector function enhanced antibodies, the HexElect® platform, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing therapeutic potency and the DuoHexaBody® platform, which enhances the potential potency of bispecific antibodies through hexamerization. The company intends to leverage these technologies to create opportunities for full or co-ownership of future products. Genmab has alliances with top tier pharmaceutical and biotechnology companies. Genmab is headquartered in Copenhagen, Denmark with sites in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.

    Seattle Genetics Forward Looking Statement

    Certain of the statements made in this press release are forward looking, such as those, among others, relating to plans to submit a Biologics License Application (BLA) to FDA under FDA's Accelerated Approval program based on the results of the innovaTV 204, 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 the possibility of delays in the submission of a BLA to the FDA, that the data from innovaTV 204 may not be sufficient to support accelerated approval of tisotumab vedotin, 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 Seattle Genetics is contained under the caption "Risk Factors" included in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 filed with the Securities and Exchange Commission. Seattle Genetics 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 Statement

    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®; HexElect®; and UniBody®. Arzerra® and Kesimpta® are trademarks of Novartis AG or its affiliates. DARZALEX® and DARZALEX FASPRO™ are trademarks of Janssen Pharmaceutica NV. TEPEZZA® is a trademark of Horizon Therapeutics plc.

    References:

    1 Van de Berg YW et al. Blood 2012;119:924.

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

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

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

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

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

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

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

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

    10 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/.

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  28. TOKYO and BOTHELL, Wash., Sept. 18, 2020 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (NASDAQ:SGEN) today announced that a phase 3 trial of PADCEV® (enfortumab vedotin-ejfv) met its primary endpoint of overall survival compared to chemotherapy. The results were reviewed by an independent Data Monitoring Committee following a planned interim analysis. The global EV-301 clinical trial 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.

    TOKYO and BOTHELL, Wash., Sept. 18, 2020 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (NASDAQ:SGEN) today announced that a phase 3 trial of PADCEV® (enfortumab vedotin-ejfv) met its primary endpoint of overall survival compared to chemotherapy. The results were reviewed by an independent Data Monitoring Committee following a planned interim analysis. The global EV-301 clinical trial 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.

    In the trial, PADCEV significantly improved overall survival (OS), with a 30 percent reduction in risk of death (Hazard Ratio [HR]=0.70; [95% Confidence Interval (CI): 0.56, 0.89]; p=0.001). PADCEV also significantly improved progression-free survival (PFS), a secondary endpoint, with a 39 percent reduction in risk of disease progression or death (HR=0.61 [95% CI: 0.50, 0.75]; p<0.00001).

    For patients in the PADCEV arm of the trial, adverse events were consistent with those listed in the U.S. Prescribing Information, with rash, hyperglycemia, decreased neutrophil count, fatigue, anemia and decreased appetite as the most frequent Grade 3 or greater adverse event(s) occurring in more than 5 percent of patients.  Data from EV-301 will be submitted for presentation at an upcoming scientific congress. Patients in the chemotherapy arm of the trial will be offered the opportunity to receive PADCEV.

    The results will be submitted to the U.S. Food and Drug Administration (FDA) as the confirmatory trial following the drug's accelerated approval in 2019. EV-301 is also intended to support global registrations. 

    "EV-301 is the first randomized trial to show overall survival results compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who previously have received platinum-based treatment and a PD-1 or PD-L1 inhibitor, and we are encouraged by the potential this may have in helping patients who have otherwise limited alternatives," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "We look forward to discussing these results with global health authorities."

    "These survival results from the confirmatory trial for PADCEV are welcome news for patients whose cancer has progressed after platinum-based chemotherapy and immunotherapy," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "We continue to explore PADCEV's activity across the spectrum of urothelial cancer including its potential for use in earlier lines of therapy."

    Globally, approximately 580,000 people will be diagnosed with bladder cancer in 2020.1 Urothelial cancer accounts for 90 percent of all bladder cancers 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.2 Approximately 80 percent of people do not respond to PD-1 or PD-L1 inhibitors after a platinum-containing therapy has failed as an initial treatment for advanced disease.3

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate PADCEV 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 or PD-L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival of participants treated with PADCEV compared to those treated with chemotherapy. Secondary endpoints include progression-free survival, duration of response, and overall response rate, as well as assessment of safety/tolerability and quality-of-life parameters.

    For more information about the EV-301 clinical trial, please visit www.clinicaltrials.gov.

    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.

    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).4 PADCEV is co-developed by Astellas and Seattle Genetics.

    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 Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in people's lives. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

    About the Astellas and Seattle Genetics Collaboration

    Astellas and Seattle Genetics are co-developing PADCEV (enfortumab vedotin-ejfv) under a 50:50 worldwide development and commercialization 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.

    Seattle Genetics 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 discuss the results with global health authorities and seek global registrations; conduct of a comprehensive clinical development program for PADCEV, which includes exploring PADCEV's activity in other types of urothelial cancer and its potential for use in earlier lines of therapy; the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses, and anticipated development activities, including ongoing and future clinical trials. 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 that the data from the EV-301 trial may not be selected for presentation at scientific congresses; the possibility of delays in the submission of results to the FDA; that the results from the EV-301 trial may not be enough 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; the possibility that ongoing and subsequent clinical trials may fail to establish sufficient activity; the risk of adverse events or safety signals; and the possibility that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 filed with the Securities and Exchange Commission. Seattle Genetics 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 International Agency for Research on Cancer. Cancer Tomorrow: Bladder. http://gco.iarc.fr/tomorrow. Accessed 07-31-2020.

    2 American Society of Clinical Oncology. Bladder cancer: introduction (10-2017).

    3 Shah, Manasee V., et al "Targeted Literature Review of the Burden of Illness in UC" (PCN108), Nov 2018.

    PADCEV [package insert] Northbrook, IL: Astellas, 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:http://www.prnewswire.com/news-releases/astellas-and-seattle-genetics-announce-padcev-enfortumab-vedotin-ejfv-significantly-improved-overall-survival-in-phase-3-trial-in-previously-treated-locally-advanced-or-metastatic-urothelial-cancer-301133747.html

    SOURCE Astellas Pharma Inc.

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  29. - Trial Stopped Early Due to Positive Results at Planned Interim Analysis -

    - Data Intended to Support Global Registrations and Convert Accelerated to Regular Approval in U.S. -

    Seattle Genetics, Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced that a phase 3 trial of PADCEV® (enfortumab vedotin-ejfv) met its primary endpoint of overall survival compared to chemotherapy. The results were reviewed by an independent Data Monitoring Committee following a planned interim analysis. The global EV-301 clinical trial compared PADCEV to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy…

    - Trial Stopped Early Due to Positive Results at Planned Interim Analysis -

    - Data Intended to Support Global Registrations and Convert Accelerated to Regular Approval in U.S. -

    Seattle Genetics, Inc. (NASDAQ:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced that a phase 3 trial of PADCEV® (enfortumab vedotin-ejfv) met its primary endpoint of overall survival compared to chemotherapy. The results were reviewed by an independent Data Monitoring Committee following a planned interim analysis. The global EV-301 clinical trial 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.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200918005101/en/

    PADCEV® (enfortumab vedotin-ejfv) (Photo: Business Wire)

    PADCEV® (enfortumab vedotin-ejfv) (Photo: Business Wire)

    In the trial, PADCEV significantly improved overall survival (OS), with a 30 percent reduction in risk of death (Hazard Ratio [HR]=0.70; [95% Confidence Interval (CI): 0.56, 0.89]; p=0.001). PADCEV also significantly improved progression-free survival (PFS), a secondary endpoint, with a 39 percent reduction in risk of disease progression or death (HR=0.61 [95% CI: 0.50, 0.75]; p<0.00001).

    For patients in the PADCEV arm of the trial, adverse events were consistent with those listed in the U.S. Prescribing Information, with rash, hyperglycemia, decreased neutrophil count, fatigue, anemia and decreased appetite as the most frequent Grade 3 or greater adverse event(s) occurring in more than 5 percent of patients. Data from EV-301 will be submitted for presentation at an upcoming scientific congress. Patients in the chemotherapy arm of the trial will be offered the opportunity to receive PADCEV.

    The results will be submitted to the U.S. Food and Drug Administration (FDA) as the confirmatory trial following the drug's accelerated approval in 2019. EV-301 is also intended to support global registrations.

    "These survival results from the confirmatory trial for PADCEV are welcome news for patients whose cancer has progressed after platinum-based chemotherapy and immunotherapy," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "We continue to explore PADCEV's activity across the spectrum of urothelial cancer including its potential for use in earlier lines of therapy."

    "EV-301 is the first randomized trial to show overall survival results compared to chemotherapy in patients with locally advanced or metastatic urothelial cancer who previously have received platinum-based treatment and a PD-1 or PD-L1 inhibitor, and we are encouraged by the potential this may have in helping patients who have otherwise limited alternatives," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "We look forward to discussing these results with global health authorities."

    Globally, approximately 580,000 people will be diagnosed with bladder cancer in 2020.1 Urothelial cancer accounts for 90 percent of all bladder cancers 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.2 Approximately 80 percent of people do not respond to PD-1 or PD-L1 inhibitors after a platinum-containing therapy has failed as an initial treatment for advanced disease.3

    About the EV-301 Trial

    The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate PADCEV 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 or PD-L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival of participants treated with PADCEV compared to those treated with chemotherapy. Secondary endpoints include progression-free survival, duration of response, and overall response rate, as well as assessment of safety/tolerability and quality-of-life parameters.

    For more information about the EV-301 clinical trial, please visit www.clinicaltrials.gov.

    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.4

    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).4 PADCEV is co-developed by Astellas and Seattle Genetics.

    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 Seattle Genetics

    Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in people's lives. The company is headquartered in the Seattle, Washington area, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics 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 Seattle Genetics and Astellas Collaboration

    Seattle Genetics and Astellas are co-developing PADCEV (enfortumab vedotin-ejfv) under a 50:50 worldwide development and commercialization collaboration that was entered into in 2007 and expanded in 2009.

    Seattle Genetics 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 discuss the results with global health authorities and seek global registrations; conduct of a comprehensive clinical development program for PADCEV, which includes exploring PADCEV's activity in other types of urothelial cancer and its potential for use in earlier lines of therapy; the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses, and anticipated development activities, including ongoing and future clinical trials. 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 that the data from the EV-301 trial may not be selected for presentation at scientific congresses; the possibility of delays in the submission of results to the FDA; that the results from the EV-301 trial may not be enough 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; the possibility that ongoing and subsequent clinical trials may fail to establish sufficient activity; the risk of adverse events or safety signals; and the possibility that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 filed with the Securities and Exchange Commission. Seattle Genetics 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 International Agency for Research on Cancer. Cancer Tomorrow: Bladder. http://gco.iarc.fr/tomorrow. Accessed 07-31-2020.

    2 American Society of Clinical Oncology. Bladder cancer: introduction (10-2017).

    3 Shah, Manasee V., et al "Targeted Literature Review of the Burden of Illness in UC" (PCN108), Nov 2018.

    4 PADCEV [package insert] Northbrook, IL: Astellas, 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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  30. Companies to Co-Develop and Co-Commercialize Seattle Genetics' Antibody-Drug Conjugate Ladiratuzumab Vedotin Globally; Merck to Acquire $1 Billion Equity Stake in Seattle Genetics Common Stock

    Companies Enter Exclusive License and Co-Development Agreement to Accelerate Global Reach of TUKYSA for HER2-Postive Cancers in Regions Outside the United States, Canada and Europe

    Seattle Genetics to Host Conference Call Today at 9:00 a.m. ET

    Seattle Genetics, Inc. (NASDAQ:SGEN) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced two new strategic oncology collaborations.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200914005237/en/

    The companies will…

    Companies to Co-Develop and Co-Commercialize Seattle Genetics' Antibody-Drug Conjugate Ladiratuzumab Vedotin Globally; Merck to Acquire $1 Billion Equity Stake in Seattle Genetics Common Stock

    Companies Enter Exclusive License and Co-Development Agreement to Accelerate Global Reach of TUKYSA for HER2-Postive Cancers in Regions Outside the United States, Canada and Europe

    Seattle Genetics to Host Conference Call Today at 9:00 a.m. ET

    Seattle Genetics, Inc. (NASDAQ:SGEN) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced two new strategic oncology collaborations.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200914005237/en/

    The companies will globally develop and commercialize Seattle Genetics' ladiratuzumab vedotin, an investigational antibody-drug conjugate (ADC) targeting LIV-1, which is currently in phase 2 clinical trials for breast cancer and other solid tumors. The collaboration will pursue a broad joint development program evaluating ladiratuzumab vedotin as monotherapy and in combination with Merck's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in triple-negative breast cancer, hormone receptor-positive breast cancer and other LIV-1-expressing solid tumors. Under the terms of the agreement, Seattle Genetics will receive a $600 million upfront payment and Merck will make a $1.0 billion equity investment in 5.0 million shares of Seattle Genetics common stock at a price of $200 per share. In addition, Seattle Genetics is eligible for progress-dependent milestone payments of up to $2.6 billion.

    Separately, Seattle Genetics has granted Merck an exclusive license to commercialize TUKYSA® (tucatinib), a small molecule tyrosine kinase inhibitor, for the treatment of HER2-positive cancers, in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. Seattle Genetics will receive $125 million from Merck as an upfront payment and is eligible for progress-dependent milestones of up to $65 million.

    "Collaborating with Merck on ladiratuzumab vedotin will allow us to accelerate and broaden its development program in breast cancer and other solid tumors, including in combination with Merck's KEYTRUDA, while also positioning us to leverage our U.S. and European commercial operations," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "The strategic collaboration for TUKYSA will help us reach more patients globally and benefit from the established commercial strength of one of the world's premier pharmaceutical companies."

    "These two strategic collaborations will enable us to further diversify Merck's broad oncology portfolio and pipeline, and to continue our efforts to extend and improve the lives of as many patients with cancer as possible," said Dr. Roger M. Perlmutter, President, Merck Research Laboratories. "We look forward to working with the team at Seattle Genetics to advance the clinical program for ladiratuzumab vedotin, which has shown compelling signals of efficacy in early studies, and to bring TUKYSA to even more patients with cancer around the world."

    Ladiratuzumab Vedotin Collaboration Details

    Under the terms of the agreement, Seattle Genetics and Merck will collaborate and equally share costs on the global development of ladiratuzumab vedotin and other LIV-1-targeting ADCs. The companies have agreed to jointly develop and share future costs and profits for ladiratuzumab vedotin on a 50:50 basis worldwide. Merck will pay Seattle Genetics $600 million upfront and make a $1.0 billion equity investment in 5.0 million shares of Seattle Genetics common stock at a price of $200 per share. In addition, Seattle Genetics will be eligible to receive up to $2.6 billion in milestone payments, including $850 million in development milestones and $1.75 billion in sales milestones.

    The companies will jointly develop and commercialize ladiratuzumab vedotin and equally share profits worldwide. The companies will co-commercialize in the U.S. and Europe. Seattle Genetics will be responsible for marketing applications for approval in the U.S. and Canada, and will record sales in the U.S., Canada and Europe. Merck will be responsible for marketing applications for approval in Europe and in countries outside the U.S. and Canada, and will record sales in countries outside the U.S., Europe and Canada. Including the upfront payment, equity investment proceeds and potential milestone payments, Seattle Genetics is eligible to receive up to $4.2 billion.

    The closing of the equity investment is contingent on completion of review under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act).

    TUKYSA Collaboration Details

    Under the terms of the agreement, Merck has been granted exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. Seattle Genetics retains commercial rights and will record sales in the U.S., Canada and Europe. Merck will be responsible for marketing applications for approval in its territory, supported by the positive results from the HER2CLIMB clinical trial.

    Merck will also co-fund a portion of the TUKYSA global development plan, which encompasses several ongoing and planned trials across HER2-positive cancers, including breast, colorectal, gastric and other cancers set forth in a global product development plan. Seattle Genetics will continue to lead ongoing TUKYSA global development planning and operational execution. Merck will solely fund and conduct country-specific clinical trials necessary to support anticipated regulatory applications in its territory.

    Seattle Genetics will receive from Merck $125 million as an upfront payment and is eligible to receive progress-dependent milestones of up to $65 million. Seattle Genetics will also receive $85 million in prepaid research and development payments to be applied to Merck's global development funding obligations. In addition, Seattle Genetics would receive tiered royalties on sales of TUKYSA in Merck's territory.

    The financial impact of these collaborations is not included in Seattle Genetics' 2020 guidance.

    Seattle Genetics Conference Call Details

    Seattle Genetics' management will host a conference call to discuss these collaborations today at 6:00 a.m. Pacific Time (PT); 9:00 a.m. Eastern Time (ET). The event will be simultaneously webcast and available for replay from the Seattle Genetics website at www.seattlegenetics.com, under the Investors section. Investors may also participate in the conference call by calling 844-763-8274 (domestic) or +1 412-717-9224 (international). The conference ID is 10147850.

    About Ladiratuzumab Vedotin

    Ladiratuzumab vedotin is a novel investigational ADC targeted to LIV-1. Most metastatic breast cancers express LIV-1, which also has been detected in several other cancers, including lung, head and neck, esophageal and gastric. Ladiratuzumab vedotin utilizes Seattle Genetics' proprietary ADC technology and consists of a LIV-1-targeted monoclonal antibody linked to a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE) by a protease-cleavable linker. This novel ADC is designed to bind to LIV-1 on cancer cells and release the cell-killing agent into target cells upon internalization. Ladiratuzumab vedotin may also cause antitumor activity through other mechanisms, including activation of an immune response by induction of immunogenic cell death.

    About TUKYSA (tucatinib)

    TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth. 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 addition, TUKYSA received approval in Canada, Singapore, Australia and Switzerland under the Project Orbis initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology products among international partners. A marketing application is under review in the European Union.

    TUKYSA is being evaluated in several ongoing clinical trials and additional studies are planned. Current trials include the following:

    • HER2CLIMB-02: a randomized, double-blind phase 3 trial evaluating TUKYSA in combination with T-DM1 (trastuzumab emtansine; Kadcyla®) versus T-DM1 in first- and second-line metastatic HER2-positive breast cancer.
    • CompassHER2 RD: a randomized, double-blind phase 3 trial of TUKYSA in combination with T-DM1 versus T-DM1 in the adjuvant breast cancer setting for patients at high risk of relapse.
    • MOUNTAINEER: a pivotal phase 2 trial evaluating TUKYSA in combination with trastuzumab (Herceptin®) in metastatic HER2-positive colorectal cancer.
    • MOUNTAINEER-02: a randomized phase 2/3 trial evaluating TUKYSA in combination with trastuzumab, ramucirumab and paclitaxel versus ramucirumab and paclitaxel in second-line metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma (GEC).
    • Gastrointestinal cancers