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Astellas Pharmaceutical Group (Tokyo Stock Exchange: 4503, President and Chief Executive Officer: Naoki Okamura, "Astellas") announced on August 20 that the Center for Drug Evaluation (CDE) of the China National Drug Administration has approved Vientumab for injection. Vientumab is intended for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) in adult patients who have previously received platinum-containing chemotherapy and PD-1 or PD-L1 inhibitors.

Urothelial carcinoma is a severe and prevalent cancer affecting the lower urinary tract (including the bladder and urethra) as well as the upper urinary tract (including the ureters and renal pelvis). In 2022, more than 92,000 individuals in China were diagnosed with bladder cancer, and approximately 41,000 succumbed to the disease. For patients with advanced or metastatic urothelial cancer, survival rates are particularly poor, highlighting the urgent need for new treatments to improve patient outcomes.

Professor Guo Jun, Director of the Department of Melanoma and Sarcoma and Urologic Oncology at Peking University Cancer Hospital, emphasized the significance of this approval: "On August 13, 2024, the National Medical Products Administration (NMPA) officially approved Vientumab for injectable use in adult patients with locally advanced or metastatic urothelial carcinoma who have previously received platinum-containing chemotherapy and PD-1 or PD-L1 inhibitors. This approval is based on a global Phase 3 registration study and a bridging study in the Chinese population. This marks a landmark event for the accessibility of new antibody-drug conjugate (ADC) therapies for the entire population of UC."

Ahsan Arozullah, MD, MPH, senior vice president and head of oncology area Development at Astellas, expressed the company's commitment: "We are dedicated to advancing scientific research that will significantly alter the course of cancer care globally. The approval of Vientumab by the CDE of the China National Drug Administration introduces another treatment option for patients with locally advanced or metastatic urothelial carcinoma in China, potentially leading to better treatment outcomes."

The approval of Vientumab is supported by data from the global study EV-301 and the Chinese bridging study EV-203. The randomized Phase 3 study EV-301 supports the worldwide registration of Vientumab. The EV-203 study (NCT04995419) is a single-arm, open-label, multicenter phase 2 study involving Chinese patients with locally advanced or metastatic urothelial carcinoma who had previously been treated with PD-1/PD-L1 inhibitors and platinum-containing chemotherapy. Results from EV-203 revealed that the study met its primary endpoint, with a confirmed objective response rate (ORR) of 37.5% as assessed by an Independent Review Committee (IRC) in patients treated with Vientumab monotherapy compared to historical controls. The efficacy and pharmacokinetic data from the study aligned with global data, and safety results indicated mainly grade 1-2 treatment-related adverse events.

Astellas has already factored in the impact of the approval of Vientumab in China in its financial forecast for the fiscal year 2024 (ending March 31, 2025).

The EV-203 Phase II clinical trial (NCT04995419) was conducted in China to evaluate the efficacy, safety, and pharmacokinetics of Vientumab in Chinese patients. The study enrolled 40 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. The primary endpoint was achieved, with a confirmed objective response rate in patients treated with Vientumab monotherapy of 37.5%. No new safety signals were found, with most adverse events being grade 1-2.

The EV-301 clinical trial (NCT03474107) is a global Phase III trial designed to evaluate the efficacy of Vientumab compared to chemotherapy in patients with locally advanced or metastatic urothelial carcinoma. The primary endpoint was overall survival, and secondary endpoints included progression-free survival, overall response rate, and safety/tolerability. The results demonstrated longer median overall survival and progression-free survival in the Vientumab group compared to the chemotherapy group, with similar rates of treatment-related adverse events in both groups. These findings were published in the New England Journal of Medicine.

In China, bladder cancer ranked 11th among all cancers in 2022, with over 92,000 new cases that year. Continuous treatment and monitoring make bladder cancer one of the most expensive cancers to treat.

Vientumab is an innovative antibody-drug conjugate (ADC) targeting the Nectin-4 protein, which is highly expressed in bladder cancer. By binding to cells with the Nectin-4 protein, the anti-tumor component monomethyloratatin E (MMAE) is internalized and released into cells, causing cell cycle arrest and programmed cell death, thus exerting its anticancer activity.

Ongoing research includes the EV-302, EV-103, EV-104, EV-304, EV-303, and EV-202 clinical trials, which are exploring the efficacy of Vientumab in various combinations and stages of urothelial cancer, as well as other advanced solid tumors.