FDA Accepts Astellas' Resubmitted Biologics License for Zolbetuximab, Sets New Action Date

On May 30, 2024, Astellas Pharma Inc. announced that the U.S. Food and Drug Administration (FDA) has acknowledged the resubmission of their Biologics License Application (BLA) for zolbetuximab. This investigational claudin (CLDN) 18.2-targeted monoclonal antibody is intended for first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma, provided the tumors are CLDN18.2 positive. If approved, zolbetuximab would be the first CLDN18.2-targeted treatment for this patient group in the United States. The FDA has set a new target action date of November 9, 2024, under the Prescription Drug User Fee Act (PDUFA).

In the United States, gastric cancer remains a significant health issue, with an estimated 26,890 new diagnoses and 10,880 deaths anticipated in 2024. Gastric cancer often remains undiagnosed until it has reached an advanced or metastatic stage due to early-stage symptoms resembling more common digestive conditions. The five-year relative survival rate for metastatic gastric cancer patients is notably low at 7%.

Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development at Astellas, expressed the company's commitment to developing new targeted therapies for challenging cancers. This FDA acknowledgment represents a critical step towards providing a new treatment option for advanced gastric or GEJ cancer patients in the U.S.

Astellas resubmitted the zolbetuximab BLA on May 9, 2024, following a complete response letter from the FDA dated January 4, 2024. This letter cited manufacturing deficiencies at a third-party facility identified during pre-license inspection but did not raise concerns about the clinical data, efficacy, or safety of zolbetuximab. The FDA did not request additional clinical studies to support the BLA.

The BLA for zolbetuximab is based on the results from the Phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT trial examined zolbetuximab combined with mFOLFOX6 (a chemotherapy regimen including oxaliplatin, leucovorin, and fluorouracil) against a placebo with mFOLFOX6. The GLOW trial compared zolbetuximab plus CAPOX (a chemotherapy regimen including capecitabine and oxaliplatin) to placebo plus CAPOX. Both trials found that about 38% of screened patients had CLDN18.2 positive tumors.

In Japan, the Ministry of Health, Labour and Welfare approved zolbetuximab on March 26, 2024, making it the first CLDN18.2-targeted treatment available for patients with advanced or recurrent gastric cancer. Astellas has filed applications for zolbetuximab with other regulatory agencies globally, and reviews are ongoing.

Zolbetuximab is an investigational claudin 18.2-directed cytolytic antibody being studied in combination with fluoropyrimidine- and platinum-based chemotherapies for treating HER2-negative gastric or GEJ adenocarcinoma. It operates by targeting and binding to the CLDN18.2 protein, leading to the destruction of cancer cells. However, there is no assurance that zolbetuximab will receive regulatory approval in the U.S. or become commercially available.

Gastric cancer, also known as stomach cancer, is the fifth most common cancer worldwide. In the U.S., approximately 130,263 people live with gastric cancer, categorizing it as a rare disease. Symptoms include indigestion, abdominal pain, nausea, vomiting, and more severe signs like unexplained weight loss and blood in vomit or stool. Risk factors include older age, male gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease (GERD). GEJ adenocarcinoma starts where the esophagus meets the stomach, and early symptoms often lead to late-stage diagnoses.

Astellas continues to investigate the potential of zolbetuximab and other CLDN18.2-targeted therapies through ongoing clinical trials and exploratory studies. The company remains at the forefront of introducing innovative treatments for patients with significant unmet needs.