Astellas and Seagen Secure FDA Priority Review for PADCEV in PD-(L)1 Inhibitor–Refractory Urothelial Cancer

April 20, 2021 News /BioonBIOON/ -- SeattleGeneticsSeagen and Astellas recently announced jointly that the U.S. Food and Drug Administration (FDA) has accepted two supplemental Biologics License Applications (sBLAs) for the antibody-drug conjugate (ADC) Padcev (enfortumab vedotin) for the treatment of urothelial cancer (UC), which will be reviewed as part of the Real-Time Oncology Review (RTOR) pilot program. Both sBLAs have been granted priority review, with a target action date of August 17, 2021. The review of these two sBLAs will also take place in the United StatesFDATumorReviewed under the Oribis project initiated by the Center of Excellence (OCE).

FDAThe RTOR pilot project aims to explore a more efficient review process to ensure timely patient access to safe and effective therapies, while the Orbis Project facilitates simultaneous submission and review by participating international regulatory authorities.TumorThe drug provides a collaborative framework.

Of the two sBLAs, the first sBLA was based on data from the Phase 3 EV-301 trial and aimed to convert the accelerated approval of Padcev to regular approval. The second sBLA was based on data from Cohort 2 of the pivotal EV-201 trial and aimed to expand the current drug label to include patients with locally advanced or metastatic UC who had previously received one PD-1/L1 inhibitor and were ineligible for cisplatin therapy. Data from the EV-301 trial and EV-201 Cohort 2 have been presented at the 2021 American Society of Clinical OncologyTumorPresented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GCS).

Bladder Cancer - (Image source: medscape.com)

Urothelial carcinoma (UC) is the most common type of bladder cancer, accounting for approximately 90% of bladder cancer cases. 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 found 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 was 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 have been treated with a platinum-containing chemotherapy regimen in the neoadjuvant/adjuvant setting or for locally advanced or metastatic disease.

It is worth mentioning that,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 aforementioned UC patients.

In March this year, Padcev was submitted for marketing approval in the European Union and Japan. If approved, it will become the first antibody-drug conjugate (ADC) therapy for urothelial carcinoma (UC) in Europe and Japan.

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 with the chemotherapy group.

The second sBLA is based on the 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/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 U.S.FDA Acceptance of Two Supplemental Biologics License applications for PADCEV (enfortumab vedotin-ejfv) in Locally Advanced or Metastatic Urothelial Cancer