Astellas and Seagen Announce CDE Acceptance of BLA for Enfortumab Vedotin in Previously Treated Locally Advanced or Metastatic Urothelial Cancer in China

- The clinical data from Chinese patients submitted is consistent with the global data and supports enfortumab vedotin as a platinum-free therapy for the treatment of patients with locally advanced or metastatic urothelial cancer who have previously received PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

March 10, 2023, Tokyo and WashingtonBosaiAstellas Pharma, Inc. (TSE:4503, President and CEO: Dr. Kenji Yasukawa, "Astellas"), Seagen, Inc. (NASDAQ: SGEN) announced today that the National Medical Products Administration of ChinaManagementThe Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) has accepted the Biologics License Application (BLA) for enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer (la/mUC) who have previously received PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Therapeutic Area Development at Astellas, stated, "In 2020, there were nearly 86,000 new cases of bladder cancer in China. We are working closely with the NMPA and look forward to bringing this innovative drug to patients in China as soon as possible. Enfortumab vedotin has become a second- and third-line therapy for many patients globally with locally advanced or metastatic urothelial cancer who have been previously treated. If approved, it will provide a new treatment option for patients in China."

The Biologics License Application for Enfortumab Vedotin is based on data from a single-arm, open-label, multicenter Phase II clinical trial [EV-203 trial (NCT04995419)]. This trial aimed to evaluate the efficacy, safety, and pharmacokinetic profile of Enfortumab Vedotin in Chinese patients with locally advanced or metastatic urothelial carcinoma who were previously treated with PD-1/PD-L1 inhibitors and platinum-based chemotherapy. The results showed that EV-203 met its primary endpoint, with the objective response rate (ORR) confirmed by an Independent Review Committee (IRC) reachingStatisticsStatistical significance. EV-203 is a bridging study of the EV-301 trial and Cohort 1 of the EV-201 trial, with efficacy and pharmacokinetic data consistent with global data. The EV-301 trial is a randomized Phase III study, the results of which supported the submission of enfortumab vedotin for global marketing authorization.

Please see important safety information at the end of this press release, includingBlack Box Warning,Obtain additional safety information related to enfortumab vedotin, including severe skin reactions.

Enfortumab vedotin monotherapy and its combination with other therapies are part of a clinical development program aimed at addressing the comprehensive management of urothelial cancer, as well as unmet treatment needs in other solid tumors.

About Bladder Cancer and Urothelial Carcinoma

It is reported that there are approximately 573,000 new cases of bladder cancer worldwide each year, with 212,000 deaths.

Urothelial carcinoma accounts for 90% of all bladder cancer cases and can also occur in the renal pelvis, ureter, and urethra. Approximately 12% of cases are locally advanced or metastatic urothelial carcinoma at the time of diagnosis.

In China, the incidence rate of bladder cancer ranked 12th among all cancers in 2020, with an estimated 85,649 new cases. The five-year prevalence rate of bladder cancer in China is estimated at 16.26/100,000, equating to 235,393 cases.

About the EV-203 Trial

EV-203 Trial (NCT04995419) is a Phase II, multi-center, single-arm bridging study conducted in China, aiming to evaluate the efficacy, safety, and pharmacokinetic profile of enfortumab vedotin in Chinese patients. The study enrolled a total of 40 patients.

About EV-301 Trial

The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized Phase III clinical trial designed to evaluate the efficacy of enfortumab vedotin compared to physician’s choice of chemotherapy (docetaxel, paclitaxel, or vinflunine) in patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/PD-L1 inhibitor and platinum-based chemotherapy. The trial enrolled 608 patients, with overall survival as the primary endpoint and secondary endpoints including progression-free survival, overall response rate, duration of response, disease control rate, as well as safety/tolerability assessments.Quality of LifeParameter Evaluation.

About the EV-201 Trial

The EV-201 trial (NCT03219333) is a single-arm, multi-cohort, multi-center, pivotal Phase II clinical trial for patients with locally advanced or metastatic urothelial carcinoma who have previously received PD-1 or PD-L1 inhibitor treatment, including patients previously treated with platinum-based chemotherapy (Cohort 1) and patients who have not received platinum-based chemotherapy and are cisplatin-ineligible (Cohort 2). This trial recruited patients across multiple centers globally, with 125 patients in Cohort 1 and 89 patients in Cohort 2. The primary endpoint is the objective response rate confirmed by blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety, and tolerability.

The clinical trial results of EV-301 and EV-201 Cohort 2 supported the U.S. Food and Drug Administration's regular approval of enfortumab vedotin-ejfv in July 2021. Furthermore, the results of EV-301 and EV-201 Cohort 1 served as core data to support the submission of marketing authorization applications for enfortumab vedotin in global markets, including the European Union, Japan, and Singapore.

Aboutenfortumab vedotin

Enfortumab vedotin is a first-in-class antibody-drug conjugate (ADC) that directly targets Nectin-4, a protein located on the cell surface and highly expressed in bladder cancer. Non-clinical data show that the anti-cancer activity of PADCEV is due to its binding to cells expressing the Nectin-4 protein, followed by internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, leading to cell cycle arrest and programmed cell death (apoptosis).