Astellas and Seagen Submit Two sBLAs to FDA for PADCEV in PD-(L)1 Inhibitor–Refractory Urothelial Cancer

Bladder Cancer - (Image source: medscape.com)

February 19, 2021 /BioonBIOON/ -- SeattleGeneticsSeagen, Inc. and Astellas Pharma, Inc. recently jointly announced the completion of submission to the U.S. Food and Drug Administration (FDA) submitted two supplemental Biologics License Applications (sBLAs) for the antibody-drug conjugate (ADC) Padcev (enfortumab vedotin). One application, based on the Phase 3 EV-301 trial, aims to convert the accelerated approval of Padcev to regular approval. The second application, based on Cohort 2 of the pivotal EV-201 trial, seeks to expand the current labeling to include patients with locally advanced or metastatic urothelial carcinoma (UC) who have previously received a PD-1/PD-L1 inhibitor and are ineligible for cisplatin-based therapy.

FDAin real timeTumorReview of these two applications under the Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to explore a more efficient review process to ensure timely patient access to safe and effective therapies.

Padcev is a first-in-class antibody-drug conjugate (ADC) that targets a cell surface protein highly expressed in bladder cancer. The drug consists of enfortumab, a human IgG1 monoclonal antibody targeting Nectin-4, conjugated to the cytotoxic agent MMAE (monomethyl auristatin E), a microtubule-disrupting agent. Nectin-4 is a protein expressed in various solid tumors, including urothelial carcinoma (UC).TumorTherapeutic targets with moderate-to-high expression. In this drug, the ADC linker technology is from Seattle.HeredityAstellas is responsible for target identification.

In December 2019, Padcev received U.S.FDAAccelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC, the most common type of bladder cancer), specifically those who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy regimen in the neoadjuvant/adjuvant setting or for the treatment of locally advanced or metastatic disease.

Notably, Padcev is the first antibody-drug conjugate (ADC) approved for the treatment of urothelial carcinoma (UC), and the first drug approved for patients with locally advanced or metastatic UC who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. The drug was approved through the FDA’s Priority Review program. Previously,FDAPadcev Has Been Granted Breakthrough Therapy Designation for the Treatment of the Above-Mentioned UC Patients.

The sBLA seeking regular approval for Padcev is based on data from the global Phase 3 EV-301 confirmatory trial. This trial compared Padcev with chemotherapy in adult patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based chemotherapy and a PD-1/L1 inhibitor. The results showed that, with a median follow-up of 11.1 months, Padcev significantly prolonged overall survival (median OS: 12.88 months vs. 8.97 months; HR=0.70; p=0.001) and progression-free survival (median PFS: 5.55 months vs. 3.71 months; HR=0.62; p<0.001) compared to the chemotherapy group.

The second sBLA is based on results from Cohort 2 of the pivotal Phase 2 EV-201 trial. This cohort enrolled patients with locally advanced or metastatic urothelial carcinoma who had previously received one PD-1/PD-L1 inhibitor and were ineligible for cisplatin-based therapy. The results showed that among patients treated with Padcev, the confirmed objective response rate (ORR) was 52%, including a complete response (CR) rate of 20%; the median duration of response (mDOR) was 10.9 months, and the median progression-free survival (mPFS) and median overall survival (mOS) were 5.8 months and 14.7 months, respectively. (Bioon.com)

Original Source: Astellas and Seagen Announce Submission of Two Supplemental Biologics License Applicationsapplications to the U.S. FDA for PADCEV® (enfortumab vedotin-ejfv) in Locally Advanced or Metastatic Urothelial Cancer