Seattle Genetics and Astellas' Padcev Wins Breakthrough Therapy Designation in Bladder Cancer

Bladder Cancer

Bladder cancer drug Padcev, which was approved by the U.S. Food and Drug Administration in December, secured Breakthrough Therapy designation for the treatment of patients with another type of bladder cancer.

Seattle Genetics and Astellas Pharma, the co-developers of Padcev (enfortumab vedotin-ejfv) said the new designation was awarded to the bladder cancer drug in combination with Merck’s checkpoint inhibitor Keytruda for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. The Breakthrough Therapy designation was granted based on results from the dose-escalation cohort and expansion cohort A of the phase Ib/II trial EV-103, evaluating patients in this setting with the combination treatment. The FDA’s Breakthrough Therapy process is designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition.

Initial results from the trial were presented at the European Society of Medical Oncology 2019 Congress, and updated findings at the 2020 Genitourinary Cancers Symposium. The data from the trial demonstrated the combination of Padcev and Keytruda shrank tumors in the majority of patients, resulting in a confirmed objective response rate of 73.3%. Responses included 15.6% of patients who had a complete response and 57.8% of patients who had a partial response. The median progression-free survival was 12.3 months and the 12-month overall survival rate was 81.6%, the companies announced at the 2020 symposium.

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 cancers.

Andrew Krivoshik, Oncology Therapeutic Area Head at Astellas, said the Breakthrough Therapy designation awarded to the combination treatment reflects the “encouraging preliminary evidence” of Padcev and Keytruda in this bladder cancer indication. Krivoshik said the research teams are progressing their clinical development program as quickly as possible in hopes of providing another treatment possibility for patients who are in need of effective treatment options.

“This is an important step in our investigation of PADCEV in combination with pembrolizumab as a first-line therapy for patients with advanced urothelial cancer who are unable to receive cisplatin-based chemotherapy,” Roger Dansey, Chief Medical Officer at Seattle Genetics said in a statement. “Based on encouraging early clinical activity, we recently initiated a phase 3 trial of this platinum-free combination and look forward to potentially addressing an unmet need for patients.”

It is estimated that approximately 81,000 people in the U.S. will be diagnosed with bladder cancer in 2020. Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter and urethra. The recommended first-line treatment for patients with advanced urothelial cancer is a cisplatin-based chemotherapy. However, fewer than half of patients respond to carboplatin-based regimens and outcomes are typically poorer compared to cisplatin-based regimens, the companies noted.

In December, the FDA approved Padcev for adult patients 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 setting. It was approved under the FDA’s Accelerated Review Program based on tumor response rate. Accelerated approval was granted after the companies released data from a pivotal Phase II trial in June that showed Padcev rapidly shrank tumors in most patients.

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