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Astellas Innovation Management LLC

Seattle Genetics and Astellas Announce Positive Topline Results from Pivotal Trial of Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Cancer - Companies Plan to Submit Biologics License Application Later This Year –

BOTHELL, Wash. and TOKYO, Mar 28, 2019Seattle Genetics, Inc. (Nasdaq:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced positive topline results from the first cohort of patients in a pivotal phase 2 single-arm clinical trial known as EV-201. The cohort is evaluating enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer who have received previous treatment with both platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. Results showed a 44 percent objective response rate (ORR) per blinded independent central review. The duration of response was consistent with that recently reported in the previous phase 1 study (EV-101). The most common treatment-related adverse events included fatigue, alopecia, decreased appetite, rash and peripheral neuropathy. The data will be submitted for presentation at an upcoming medical meeting. 

Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a therapeutic target that is highly expressed in multiple solid tumors including urothelial cancers. Based on preliminary results from a phase 1 trial (EV-101), enfortumab vedotin was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for patients with locally advanced or metastatic urothelial cancer whose disease has progressed during or following treatment with a PD-1 or PD-L1 inhibitor.

The companies plan to submit a Biologics License Application (BLA) to the FDA later this year based on the results from the EV-201 trial (cohort 1). A global, randomized phase 3 clinical trial (EV-301) is ongoing and intended to support global registration as well as to serve as the confirmatory randomized trial for enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. 

“Despite recent approvals of multiple checkpoint inhibitors for previously treated locally advanced or metastatic urothelial cancer, there remains a high unmet need for effective treatments upon progression after initial chemotherapy and immunotherapy,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “These results for enfortumab vedotin indicate it may be able to help patients whose urothelial cancer progresses following treatment with standard chemotherapy and a PD-1 or PD-L1 inhibitor.”

“After progression on platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, patients with locally advanced or metastatic urothelial cancer are left with no approved standard of care treatment options,” said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas. “These data are very encouraging, and we look forward to discussing the data with relevant health authorities.”

Urothelial cancer is the most common type of bladder cancer (90 percent of cases).1 In 2018, more than 82,000 people were diagnosed with bladder cancer in the United States.2 Globally, approximately 549,000 people were diagnosed with bladder cancer last year, and there were approximately 200,000 deaths worldwide.3 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.4 There are currently no approved therapies for metastatic urothelial cancer once it has progressed after chemotherapy and a PD-1 or PD-L1 inhibitor.5

In addition to the ongoing confirmatory phase 3 study intended to also support global registration, development of enfortumab vedotin is underway in earlier lines of treatment for locally advanced or metastatic urothelial cancer, including in newly diagnosed patients in combination with pembrolizumab and/or platinum chemotherapy.