Astellas Resubmits BLA for Zolbetuximab, Aiming for First-in-Class CLDN18.2-Targeted Therapy in the U.S.

Recently, Astellas Pharma, Inc. announced that the U.S. Food and Drug Administration (FDA) has acknowledged the resubmission of the company’s Biologics License Application (BLA) for zolbetuximab. Zolbetuximab is an investigational first-in-class monoclonal antibody targeting Claudin (CLDN)18.2, intended for the first-line treatment of patients with CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. If approved, zolbetuximab will become the first targeted therapy option in the United States for the CLDN18.2 patient population. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a new target action date for November 9, 2024.

In the United States, it is estimated that 26,890 people will be diagnosed with stomach cancer in 2024, and 10,880 people will die from the disease.¹The symptoms of early gastric cancer often overlap with more common benign gastric diseases, often leading to the diagnosis of gastric cancer at an advanced or metastatic stage, or after the cancer cells have spread from the primary tumor site to other tissues or organs in the body.²Just diagnosed. The five-year relative survival rate for patients with metastatic gastric cancer is only 7%.¹

Zolbetuximab BLA Resubmitted on May 9, 2024. A Complete Response Letter was issued by the U.S. FDA on January 4, 2024, due to deficiencies in third-party manufacturing identified during the pre-approval inspection. The FDA did not raise any concerns related to zolbetuximab's clinical data (including efficacy or safety) and did not request additional clinical studies to support the BLA approval.

This BLA submission is based on the results of the GLOW and SPOTLIGHT Phase III clinical trials.^3,4The SPOTLIGHT trial evaluated the efficacy of zolbetuximab combined with mFOLFOX6 (a combination chemotherapy regimen including oxaliplatin, leucovorin, and modified 5-fluorouracil) compared to placebo combined with mFOLFOX6. The GLOW trial assessed the efficacy of zolbetuximab combined with CAPOX (a combination chemotherapy regimen including capecitabine and oxaliplatin) compared to placebo combined with CAPOX.

In the GLOW and SPOTLIGHT clinical trials, approximately 38% of tumor patients participating in the trials met the positive criteria for CLDN18.2 expression (defined as moderate to strong CLDN18 membrane staining in ≥75% of tumor cells), as determined by a validated immunohistochemical analysis.^3,4

On March 26, 2024, Japan's Ministry of Health, Labour and Welfare (MHLW) approved the marketing of zolbetuximab, making it the first and currently the only approved treatment targeting CLDN18.2-positive, unresectable, advanced or recurrent gastric cancer patients.⁵Astellas has also submitted new drug marketing applications for zolbetuximab to regulatory authorities around the world, and these applications are currently under review.

Astellas has already reflected the impact of the FDA's confirmation of the resubmission of the zolbetuximab BLA in its financial forecast for the fiscal year 2024 (ending March 31, 2025).

About Zolbetuximab

Zolbetuximab is a cytolytic antibody targeting claudin 18.2, being used in combination with fluoropyrimidine- and platinum-based chemotherapy for the first-line treatment of adult patients with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive, advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. As an investigational first-in-class monoclonal antibody (mAb), zolbetuximab targets and binds to CLDN18.2, a transmembrane protein. In preclinical studies, zolbetuximab eliminated CLDN18.2-positive cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).⁶. There is no guarantee that the drug will receive regulatory approval in the United States or be used for the indications under investigation and enter the commercial market.

Editor: Muyan

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