SGEN Seagen Inc.

153.39
+6.44  (+4%)
Previous Close 146.95
Open 152
52 Week Low 133.2
52 Week High 213.94
Market Cap $27,836,768,688
Shares 181,477,076
Float 65,914,277
Enterprise Value $24,195,193,318
Volume 1,447,130
Av. Daily Volume 748,287
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Upcoming Catalysts

Drug Stage Catalyst Date
Tisotumab Vedotin
Cervical Cancer
PDUFA priority review
PDUFA priority review
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Drug Pipeline

Drug Stage Notes
PADCEV (enfortumab vedotin) - EV-301
Urothelial cancer
Approved
Approved
FDA approval announced July 9, 2021.
PADCEV (enfortumab vedotin) and KEYTRUDA (pembrolizumab) - EV-103
Urothelial cancer
Phase 1/2
Phase 1/2
Phase 1/2 data presented at ASCO June 4-8, 2021.
PADCEV (enfortumab vedotin) - EV-202
Solid tumors
Phase 2
Phase 2
Phase 2 trial initiated January 2020.
PADCEV (enfortumab vedotin)
Urothelial cancer
Approved
Approved
FDA Approval announced December 18, 2019.
ADCETRIS (brentuximab vedotin)
Frontline CD30-positive mature T-cell lymphomas - cancer
Approved
Approved
FDA Approval announced November 16, 2018.
ADCETRIS (brentuximab vedotin)
Post-transplant Hodgkin lymphoma (HL) cancer
Approved
Approved
Approved August 17, 2015.
ADCETRIS (brentuximab vedotin)
Hodgkin lymphoma and Anaplastic large cell lymphoma
Approved
Approved
Approval announced August 19, 2011.
ADCETRIS (brentuximab vedotin)
Cancer - ALCANZA trial for relapsed CD30-positive cutaneous T-cell lymphoma
Approved
Approved
Approval announced November 9, 2017.
ADCETRIS (brentuximab vedotin)
Frontline Hodgkin lymphoma
Approved
Approved
sBLA approval announced March 20, 2018. PDUFA date under priority review was May 1, 2018.
Polatuzumab vedotin and bendamustine plus RITUXAN (rituximab)
Diffuse large B-cell lymphoma (DLBCL)
Approved
Approved
FDA approval announced June 10, 2019.
BLENREP (belantamab mafodotin)
Multiple myeloma
Approved
Approved
FDA approval granted August 5, 2020.
TUKYSA (Tucatinib) and HERCEPTIN (Trastuzumab) and XELODA (capecitabine)
HER2+ Metastatic Breast Cancer (MBC)
Approved
Approved
FDA Approval announced April 17, 2020.
Tucatinib - MOUNTAINEER
HER2 amplified metastatic colorectal cancer
Phase 2
Phase 2
Phase 2 enrollment to be completed by end of 2021.
Tisotumab Vedotin (innovaTV 301)
Cervical Cancer
Phase 3
Phase 3
Phase 3 trial initiation announced January 5, 2021.
SEA-TGT
Solid tumors
Phase 1
Phase 1
Phase 1 trial initiation announced June 18, 2020.
SGN-B6A
Solid Tumors
Phase 1
Phase 1
Phase 1 trial initiation announced June 18, 2020.
Tucatinib + ado-trastuzumab emtansine (T-DM1, Kadcyla), - HER2CLIMB-02
HER2+ Metastatic Breast Cancer (MBC)
Phase 3
Phase 3
Phase 3 trial initiation announced October 10, 2019.
Vadastuximab Talirine (CASCADE)
Acute myeloid leukemia (AML) - cancer
Phase 3
Phase 3
Phase 3 trial discontinued due to higher rate of deaths - June 19, 2017.

Latest News

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

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

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

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

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

    "The commercial…

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

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

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

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

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

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

    PROGRAM HIGHLIGHTS

    PADCEV

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

    TUKYSA

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

    ADCETRIS

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

    Tisotumab Vedotin

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

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

    SECOND QUARTER AND SIX-MONTHS 2021 FINANCIAL RESULTS

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

    • Net Product Sales:

    Three months ended June 30,

     

    Six months ended June 30,

    (dollars in millions)

    2021

     

    2020

    % Change

     

    2021

     

    2020

    % Change

    Total Net Product Sales

    $

    347.3

     

     

    $

    240.5

     

    44%

     

    $

    649.9

     

     

    $

    439.0

     

    48%

    ADCETRIS

    181.9

     

     

    167.5

     

    9%

     

    344.5

     

     

    331.6

     

    4%

    PADCEV

    82.4

     

     

    57.2

     

    44%

     

    152.2

     

     

    91.6

     

    66%

    TUKYSA

    83.0

     

     

    15.8

     

    427%

     

    153.3

     

     

    15.8

     

    873%

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

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

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

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

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

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

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

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

    2021 FINANCIAL OUTLOOK

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

    Revenues

    ADCETRIS net product sales

    $675 million to $700 million

    PADCEV net product sales

    $310 million to $325 million

    TUKYSA net product sales

    $300 million to $315 million

    Royalty revenues

    $125 million to $135 million

    Collaboration and license agreement revenues

    Less than $20 million

    Operating expenses and other costs

    Cost of Sales

    $270 million to $300 million

    R&D expenses

    $900 million to $1,000 million

    SG&A expenses

    $650 million to $725 million

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

    $225 million to $245 million

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

    Conference Call Details

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

    About Seagen

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

    Forward-Looking Statements

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

    Seagen Inc.

    Condensed Consolidated Statements of Operations

    (Unaudited)

    (In thousands, except per share amounts)

     

     

    Three Months Ended June 30,

     

    Six Months Ended June 30,

     

    2021

     

    2020

     

    2021

     

    2020

    Revenues:

     

     

     

     

     

     

     

    Net product sales

    $

    347,338

     

     

    $

    240,465

     

     

    $

    649,926

     

     

    $

    438,979

     

    Royalty revenues

    36,296

     

     

    31,235

     

     

    63,514

     

     

    51,595

     

    Collaboration and license agreement revenues

    4,844

     

     

    6,298

     

     

    7,020

     

     

    21,938

     

    Total revenues

    388,478

     

     

    277,998

     

     

    720,460

     

     

    512,512

     

    Costs and expenses:

     

     

     

     

     

     

     

    Cost of sales

    78,090

     

     

    48,244

     

     

    142,225

     

     

    77,665

     

    Research and development

    234,861

     

     

    198,077

     

     

    465,286

     

     

    393,276

     

    Selling, general and administrative

    165,130

     

     

    125,642

     

     

    324,972

     

     

    247,891

     

    Total costs and expenses

    478,081

     

     

    371,963

     

     

    932,483

     

     

    718,832

     

    Loss from operations

    (89,603

    )

     

    (93,965

    )

     

    (212,023

    )

     

    (206,320

    )

    Investment and other income, net

    5,027

     

     

    72,775

     

     

    6,027

     

     

    16,728

     

    Net loss

    $

    (84,576

    )

     

    $

    (21,190

    )

     

    $

    (205,996

    )

     

    $

    (189,592

    )

    Net loss per share - basic and diluted

    $

    (0.47

    )

     

    $

    (0.12

    )

     

    $

    (1.14

    )

     

    $

    (1.10

    )

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

    181,628

     

     

    173,406

     

     

    181,390

     

     

    172,878

     

    Seagen Inc.

    Condensed Consolidated Balance Sheets

    (Unaudited)

    (In thousands)

     

     

    June 30, 2021

     

    December 31, 2020

    Assets

     

     

     

    Cash, cash equivalents and investments

    $

    2,451,612

     

    $

    2,660,250

    Other assets

     

    1,500,546

     

     

    1,340,656

    Total assets

    $

    3,952,158

     

    $

    4,000,906

    Liabilities and Stockholders' Equity

     

     

     

    Accounts payable and accrued liabilities

    $

    433,834

     

    $

    388,138

    Long-term liabilities

     

    127,050

     

     

    124,668

    Stockholders' equity

     

    3,391,274

     

     

    3,488,100

    Total liabilities and stockholders' equity

    $

    3,952,158

     

    $

    4,000,906

     

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

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

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

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

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

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

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

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

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

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

    About the EV-301 Trial

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

    About the EV-201 Trial

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

    About PADCEV® (enfortumab vedotin-ejfv)

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

    BOXED WARNING: SERIOUS SKIN INFECTIONS

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

    U.S. Indication

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

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

    Important Safety Information 

    Warnings and Precautions  

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

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

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

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

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

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

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

    Adverse Reactions  

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

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

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

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

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

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

    Drug Interactions  

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

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

    Specific Populations 

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

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

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

    About Astellas  

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

    About Seagen  

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

    About the Astellas and Seagen Collaboration 

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

    Astellas Cautionary Notes 

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

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

    Seagen Forward Looking Statements 

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

    References

    ____________________

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

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

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

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

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

     

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

    SOURCE Astellas Pharma Inc.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    About the EV-301 Trial

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

    About the EV-201 Trial

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

    About PADCEV® (enfortumab vedotin-ejfv)

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

    BOXED WARNING: SERIOUS SKIN INFECTIONS

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

    U.S. Indication

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

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

    Important Safety Information

    Warnings and Precautions

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

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

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

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

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

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

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

    Adverse Reactions

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

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

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

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

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

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

    Drug Interactions

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

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

    Specific Populations

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

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

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

    About Seagen

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

    About Astellas

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

    About the Seagen and Astellas Collaboration

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

    Seagen Forward Looking Statements

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

    Astellas Cautionary Notes

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

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

    References


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

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

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

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

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

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

    Thursday, July 29, 2021

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

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

    About Seagen

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

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

    Thursday, July 29, 2021

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

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

    About Seagen

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

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

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

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

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

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

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

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

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

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

    Overall Survival (OS):

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

    Progression Free Survival (PFS):

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

    Safety

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

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

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

    About HER2CLIMB

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

    About HER2-Positive Breast Cancer

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

    About TUKYSA (tucatinib)

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

    U.S. Important Safety Information

    Warnings and Precautions

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



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



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

    Adverse Reactions

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

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

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

    Lab Abnormalities

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

    Drug Interactions

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

    Use in Specific Populations

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

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

    About Seagen

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

    Forward Looking Statements

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

    ____________________

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

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

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

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

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

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

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

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

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