China’s National Medical Products Administration (NMPA) has granted approval for PADCEV (enfortumab vedotin) to treat locally advanced or metastatic urothelial cancer (la/mUC) in adult patients. This significant decision follows prior treatments with platinum-containing chemotherapy and programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. The approval marks a pivotal development in the fight against this aggressive form of cancer, which affects the urinary tract and has limited treatment options.

The Urgent Need for New Treatments in Urothelial Cancer

Urothelial cancer, characterized by its high recurrence rate and resistance to conventional therapies, remains a critical health challenge. In 2022, China reported over 92,000 new cases of bladder cancer, with approximately 41,000 deaths. This high mortality rate underscores the urgent need for effective new treatments. Advanced urothelial cancer, which has spread beyond the bladder or urethra, is particularly difficult to treat, making PADCEV’s approval a beacon of hope for many patients.

Expert Reactions and Clinical Trial Insights

Professor Guo Jun, the Principal Investigator of the EV-203 trial and Director of the Department of Melanoma and Urological Oncology at Beijing Cancer Hospital, highlighted the significance of this approval. “The NMPA’s decision to approve enfortumab vedotin is a landmark achievement. It provides a new treatment option for patients who have limited choices after previous therapies,” Professor Jun remarked. The approval is based on robust data from global and local studies, including the EV-203 trial conducted specifically in China.

Professor Dingwei Ye, an Academic Leader at Fudan University-Affiliated Cancer Hospital, echoed this sentiment. “The introduction of enfortumab vedotin into the Chinese market is a major advancement. This new treatment will offer hope to patients with advanced urothelial carcinoma who have previously undergone extensive therapy.”

Clinical Trials Showcase PADCEV’s Efficacy

The NMPA’s approval is supported by results from both the global EV-301 trial and the China-specific EV-203 trial. The EV-203 trial, a Phase 2, multicenter, single-arm study, involved 40 patients with la/mUC who had previously received PD-1/PD-L1 inhibitors and platinum-based chemotherapy. The trial achieved a 37.5% objective response rate (ORR), with 2.5% of patients experiencing a complete response and 35% showing a partial response. These results align with global data, demonstrating the drug’s efficacy.

The global EV-301 trial, a Phase 3 randomized study, compared PADCEV to standard chemotherapy in 608 patients. The trial revealed that patients receiving enfortumab vedotin had a median overall survival of 12.88 months, compared to 8.97 months for those receiving chemotherapy. Additionally, progression-free survival was longer in the enfortumab vedotin group (5.55 months vs. 3.71 months). The trial’s results, published in the New England Journal of Medicine, underscore PADCEV’s potential to significantly improve patient outcomes.

Impact and Future Prospects

Astellas Pharma Inc., the manufacturer of PADCEV, has included the anticipated impact of this approval in its financial forecast for the fiscal year ending March 31, 2025. The company is committed to advancing cancer treatment worldwide and views this approval as a crucial step forward. “The approval of enfortumab vedotin by the CDE marks a significant milestone in our efforts to provide new treatment options for patients with advanced urothelial cancer,” said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Oncology Development at Astellas.

PADCEV’s Innovative Mechanism of Action

PADCEV is a first-in-class antibody-drug conjugate (ADC) targeting Nectin-4, a protein highly expressed on bladder cancer cells. The drug’s mechanism involves binding to Nectin-4-expressing cells, leading to internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE). This process results in cell cycle arrest and programmed cell death, offering a targeted approach to treating urothelial cancer.

  Astellas Pharma Inc., Beijing Cancer Hospital, China National Medical Products Administration, enfortumab vedotin, EV-203 trial, EV-301 trial, Fudan University-Affiliated Cancer Hospital, PADCEV, Peking University First Hospital, urothelial cancer