Astellas Resubmits Claudin18.2 Antibody Marketing Application

Recently, Astellas, a pharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has agreed to review the resubmitted Biologics License Application (BLA) for their investigational monoclonal antibody, zolbetuximab. This antibody targets the protein Claudin (CLDN) 18.2 and is intended for the first-line treatment of CLDN18.2-positive, HER2-negative, locally advanced, unresectable, or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

If it gains approval, zolbetuximab would be the first and only targeted therapy available for CLDN18.2-positive patients in the United States. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of November 9, 2024, for this application.

Gastric cancer is a significant health issue in the U.S., with an estimated 26,890 new cases and 10,880 deaths expected in 2024. Early-stage gastric cancer often presents with symptoms similar to less severe gastric conditions, which often leads to late-stage, metastatic diagnosis. The 5-year relative survival rate for patients with metastatic gastric cancer is a dismal 7%.

The resubmission of the zolbetuximab BLA is supported by data from the Phase 3 GLOW and SPOTLIGHT clinical trials. These trials assessed the effectiveness of zolbetuximab combined with chemotherapy, compared to a placebo with chemotherapy. Findings showed that around 38% of trial participants were CLDN18.2-positive, characterized by moderate to strong membrane staining in at least 75% of tumor cells.

In March 2024, Japan's Ministry of Health, Labor and Welfare (MHLW) approved zolbetuximab, making it the first targeted therapy for CLDN18.2-positive, unresectable, advanced, or recurrent gastric cancer in that country. Astellas has also submitted marketing applications for zolbetuximab to regulatory agencies worldwide, and these applications are currently under review.