China’s National Medical Products Administration (NMPA) Approves PADCEV™ (enfortumab vedotin) for Treatment of Locally Advanced or Metastatic Urothelial Cancer

– Approval based on the global EV-301 and China EV-203 trials, where enfortumab vedotin significantly improved overall survival (OS) and objective response rate (ORR) respectively in patients following prior treatment with platinum-based chemotherapy and PD-1/L1 inhibitors1,2

– Enfortumab vedotin will provide a much needed new treatment option for patients with locally advanced or metastatic urothelial cancer in China

TOKYO, Aug. 19, 2024 /PRNewswire/ — Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, “Astellas”) today announced that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has approved PADCEV™ (enfortumab vedotin) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) after prior treatment with platinum-containing chemotherapy and programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors.

Urothelial cancer is a debilitating and often aggressive cancer that affects both the lower urinary tract (bladder and urethra) and upper urinary tract (ureter and renal pelvis).3,4,5 Over 92,000 people were diagnosed with bladder cancer in China in 2022, and approximately 41,000 deaths were reported as a result of the disease.6 Survival rates are particularly poor with locally advanced or metastatic urothelial cancer, driving the urgent need for new therapies that extend patients’ lives.

Professor Guo Jun, Principal Investigator, EV-203 trial and Director of the Department of Melanoma and Urological Oncology, Beijing Cancer Hospital, China”On August 13, 2024, the NMPA officially approved the use of enfortumab vedotin for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (la/mUC) after prior treatment with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. This approval, based on a global Phase 3 registration study as well as a bridging study in Chinese patients, is a milestone event where patients will now have access to this new antibody-drug conjugate (ADC) treatment in China.”

Professor Dingwei Ye, Academic Leader, Department of Urology and Principal Expert, Urological Oncology MDT Management, Fudan University-Affiliated Cancer Hospital, China
“Enfortumab vedotin will benefit patients in our country, bringing a new treatment to those with locally advanced or metastatic urothelial carcinoma (la/mUC) who have previously received platinum-containing chemotherapy and PD-1/PD-L1 inhibitors.”

Professor Zhisong He, Deputy Director, Institute of Urology, Peking University First Hospital, China”Enfortumab vedotin is an ADC that is directed against Nectin-4. The approval of the EV-203 indication expands doctors’ treatment choices.”

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas”We remain committed to driving scientific progress that leads to meaningful changes in the course of cancer across the globe. The approval of enfortumab vedotin by the CDE provides patients in China with another treatment option for locally advanced or metastatic urothelial cancer, providing hope of better outcomes for those affected by this condition.”

The CDE’s approval of enfortumab vedotin is supported by data from the global EV-301 and China EV-203 trials. EV-203 serves as a bridging trial to EV-301, a Phase 3 randomized trial that has supported global registrations of enfortumab vedotin. EV-203 (NCT04995419) is a single-arm, open-label, multicenter Phase 2 trial of enfortumab vedotin in Chinese patients with la/mUC who previously received a PD-1/PD-L1 inhibitor and platinum-based chemotherapy.1 Results showed that EV-203 met its primary endpoint, demonstrating statistical significance in ORR for patients treated with enfortumab vedotin alone compared to historical controls (37.5% [n/N=15/40; 95% CI: 22.7–54.2]), as confirmed by the independent review committee.1 The efficacy and pharmacokinetic data from the trial are consistent with global data, with safety findings demonstrating that the majority of treatment related adverse events were grade 1–2.1

Astellas has already reflected the impact from the approval for enfortumab vedotin in China in its financial forecast for the current fiscal year ending March 31, 2025.

For more information, please see the press release “Astellas and Seagen Announce China’s National Medical Products Administration Accepts Biologics License Application for Enfortumab Vedotin in Certain Patients with Locally Advanced or Metastatic Urothelial Cancer” issued on March 9, 2023: https://www.astellas.com/en/news/27441

About EV-203
The China EV-203 trial is a Phase 2, multicenter, single-arm bridging trial designed to evaluate the efficacy, safety, and pharmacokinetic performance of enfortumab vedotin as a treatment for patients in China. The trial enrolled a total of 40 patients with la/mUC who previously received a PD-1/PD-L1 inhibitor and platinum-based chemotherapy.1

The trial met the primary endpoint of confirmed objective response rate (ORR) by independent review committee, achieved by 37.5% of patients who received treatment with enfortumab vedotin (n/N=15/40, 95% CI: 22.7-54.2). Complete response was achieved in 1 (2.5%) patient and partial response in 14 (35.0%) patients.1

No new safety signals were identified during the trial. Most treatment-related adverse events reported with enfortumab vedotin were grade 1–2. Two patients discontinued treatment with enfortumab vedotin due to experiencing treatment-related adverse events (acute coronary syndrome and hyperglycemia/rash).1

For more information on the EV-203 trial (NCT04995419) go to https://clinicaltrials.gov.

About EV-301
The global EV-301 trial (NCT03474107) is a multicenter, open-label, randomized Phase 3 trial designed to evaluate enfortumab vedotin versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in 608 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/PD-L1 inhibitor and platinum-containing therapies.2 The primary endpoint was overall survival and secondary endpoints included progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

Results from EV-301 showed that median overall survival was longer in the enfortumab vedotin group than in the chemotherapy group (12.88 vs. 8.97 months respectively; HR= 0.70; 95% CI: 0.56-0.89; p=0.001).2 Progression-free survival was also longer in the enfortumab vedotin group than in the chemotherapy group (5.55 vs. 3.71 months respectively; HR=0.62; 95% CI: 0.51-0.75; P