FDA Expands Indication for First-in-Class ADC Padcev (enfortumab vedotin-ejfv) in Locally Advanced or Metastatic Urothelial Cancer

On the 10th, Seagen and Astellas Pharma, Inc. jointly announced that the U.S. FDA has approved an expanded indication for its antibody-drug conjugate (ADC) Padcev (enfortumab vedotin-ejfv) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have previously received at least one prior therapy and are ineligible for cisplatin-containing chemotherapy. The press release noted that this is the first FDA-approved therapy for this patient population. Additionally, based on data from the Phase 3 EV-301 clinical trial, the FDA converted the previous accelerated approval of Padcev to a full approval.

In 2020, approximately 580,000 individuals worldwide were diagnosed with bladder cancer. Urothelial carcinoma accounts for 90% of all bladder cancers and can also arise in the renal pelvis, ureters, and urethra. The press release noted that approximately half of patients with advanced bladder cancer are ineligible for cisplatin-based chemotherapy. These patients typically receive first-line immunotherapy; however, if they do not respond to immunotherapy or experience disease recurrence, their treatment options are limited and their prognosis is poor.

Padcev is an antibody-drug conjugate that links an anti-nectin-4 monoclonal antibody to a microtubule inhibitor. Nectin-4 is a cell adhesion molecule highly expressed in urothelial carcinoma. Based on response rate data, this therapy received accelerated approval from the U.S. FDA in December 2019 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have previously received cisplatin-containing chemotherapy and a PD-1 or PD-L1 inhibitor.

The approval for the expanded indication is based on positive results with Padcev in cohort 2 of the pivotal Phase 2 clinical trial EV-201. Trial results showed that, at a median follow-up of 16 months, the objective response rate for patients treated with Padcev was 51% (95% CI: 39.8, 61.3) among patients with locally advanced or metastatic urothelial carcinoma who were previously treated with PD-1/PD-L1 inhibitors and were ineligible for cisplatin-containing chemotherapy. The median duration of response was 13.8 months (95% CI: 6.4, not yet reached).

The conversion of Padcev’s accelerated approval to full approval is based on positive data from the Phase 3 clinical trial EV-301. These data, published in *The New England Journal of Medicine*, demonstrated that Padcev extended patients’ overall survival by 3.9 months compared with chemotherapy.

“For patients with locally advanced or metastatic disease who have previously received immunotherapy and are ineligible for cisplatin-based chemotherapy, Padcev is the first FDA-approved therapy,” said Dr. Roger Dansey, Chief Medical Officer of Seagen. “Thanks to the FDA’s Real-Time Oncology Review program, we were able to bring it to these patients as quickly as possible, who have limited treatment options due to age or comorbidities.”

References:

[1] U.S. FDA Grants Regular Approval and Expands Indication for PADCEV® (enfortumab vedotin-ejfv) for Patients with Locally Advanced or Metastatic Urothelial Cancer. Retrieved July 9, 2021, from https://www.businesswire.com/news/home/20210709005414/en

▽Follow [WuXi KangVirtue】WeChat Official Account