Astellas Submits New Drug Application Targeting First ADC Approval for Metastatic Urothelial Cancer in Japan

Urothelial cancer accounts for up to 90% of bladder cancers. Each year, 24,300 new cases and 200,000 deaths are reported in Japan. It is especially challenging for advanced and metastatic urothelial cancer patients because of the costly treatment and poor five-year survival rate, which is a mere 7%. What’s worse, patients who progressed after chemotherapy or immunotherapy don’t have a standard treatment.

Targeting First Japanese Approval for ADC in Urothelial Cancer

Astellas Pharma has submitted a New Drug Application (NDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer that has progressed after anti-cancer medication.

Enfortumab vedotin is an antibody-drug conjugate (ADC) that targets a highly expressed protein in bladder cancer called Nectin-4. It can bind to Nectin-4 and release anti-tumor agent monomethyl auristatin E (MMAE) to stop the cell from reproduction and begin apoptosis.

It should be noted that if the drug is approved, it will be the first ADC approved for the indication in Japan.

Meeting Primary Endpoints in Two Clinical Trials

The NDA comes after enfortumab vedotin met the primary endpoints in two clinical trials conducted in Japan.

In Phase 2 clinical trial EV-201 (NCT03219333), enfortumab vedotin was examined with 2 groups of patients: those who have also been treated with platinum-containing chemotherapy and those who have not received platinum-containing chemotherapy and who are ineligible for cisplatin. The primary endpoint is the ORR per blinded independent central review.

In Phase 3 clinical trial EV-301 (NCT03474107), enfortumab vedotin was evaluated with about 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1 or PD-L1 inhibitor and platinum-based therapies. It is compared to the control group that took physician’s choice of chemotherapy like docetaxel, paclitaxel, or vinflunine.

After 11 months of follow-up, enfortumab vedotin showed better median OS (3.9 months), progression-free survival (5.6 months), ORR (40.6%), and DCR (71.9%) than chemotherapy.

Andrew Krivoshik, M.D., Ph.D., Senior Vice President, and Oncology Therapeutic Area Head, Astellas said, “Based on data from two global clinical trials, and following the Ministry of Health, Labour and Welfare’s review, enfortumab vedotin may offer a new option for these patients.”

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Author

Tyler Chen

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