Astellas Gets CHMP Approval for PADCEV with KEYTRUDA for Advanced Bladder Cancer

Astellas Pharma Inc. has announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has given a positive opinion recommending the approval of PADCEV™ (enfortumab vedotin) in combination with KEYTRUDA® (pembrolizumab) for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer who are suitable candidates for platinum-containing chemotherapy.

This recommendation is based on data from the Phase 3 EV-302 clinical trial, which showed that the combination therapy nearly doubled the median overall survival compared to the current standard platinum-containing chemotherapy. Specifically, the trial revealed that patients treated with enfortumab vedotin and pembrolizumab had a median overall survival of 31.5 months compared to 16.1 months for those on chemotherapy. This translates to a 53% reduction in the risk of death. Additionally, the median progression-free survival was 12.5 months for the combination therapy versus 6.3 months for chemotherapy, indicating a 55% reduction in the risk of cancer progression or death.

Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Oncology Development at Astellas, highlighted that current treatment options for unresectable or metastatic urothelial cancer are largely limited to platinum-containing chemotherapy. He emphasized that the CHMP’s positive opinion acknowledges the potential of this new combination to transform the first-line treatment landscape for this patient population.

Bladder cancer, particularly urothelial cancer, is a significant health concern in Europe, which has the highest incidence rate of this disease globally. Each year, over 165,000 people in the European Union are diagnosed with bladder cancer, resulting in more than 50,000 deaths annually. The disease often severely impacts both physical functioning and the quality of life of patients and caregivers, with late detection and complex diagnostic pathways exacerbating these issues. 

Following the CHMP's positive opinion, the European Commission will review the recommendation and has the authority to approve the combination therapy for use in the 27 EU member states, as well as in Iceland, Liechtenstein, and Norway. This approval process follows the U.S. Food and Drug Administration's (FDA) decision in December 2023 to approve enfortumab vedotin in combination with pembrolizumab for treating adult patients with locally advanced or metastatic urothelial cancer.

PADCEV™ is already approved in the EU as a monotherapy for adults with locally advanced or metastatic urothelial cancer who have previously been treated with platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. The ongoing EV-302 trial supports this new combination therapy, with 886 patients enrolled who were eligible for cisplatin- or carboplatin-containing chemotherapy. The trial’s primary endpoints included overall survival and progression-free survival, with secondary endpoints focusing on overall response rate, duration of response, and safety.

The combination therapy's safety profile was consistent with previous findings, with common severe adverse events including maculo-papular rash, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia. No new safety concerns were identified.

Bladder cancer, particularly urothelial cancer, accounts for 90% of all bladder cancers and can also occur in other parts of the urinary tract. It is a costly disease due to the lifelong need for treatment and surveillance. PADCEV™ works by targeting Nectin-4, a protein highly expressed in bladder cancer cells, and delivering a cytotoxic agent that inhibits cell reproduction and induces cell death.

Multiple ongoing trials are further evaluating enfortumab vedotin in combination with pembrolizumab across various stages of urothelial cancer and other solid tumors, including phases 3 clinical trials for muscle-invasive bladder cancer and head and neck squamous cell carcinoma. These expansive research efforts aim to validate the efficacy and safety of this combination therapy in broader cancer treatment applications.

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