FDA Issues CRL for Zolbetuximab Biologics License Application


The FDA cited issues with a third-party manufacturing company. Zolbetuximab is being reviewed to treat patients with stomach cancer.

The FDA has issued a complete response letter for Astellas Pharma’s biologics license application for zolbetuximab to treat patients with advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The FDA indicated the CRL was because of unresolved deficiencies following its inspection of a third-party manufacturing facility. Regulators did not raise any concerns related to the clinical data of zolbetuximab and is not requesting additional clinical studies. Astellas is working closely with the FDA and the manufacturer to resolve the issues.

In the United States, it is estimated that 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023. These cancers are often diagnosed in the advanced or metastatic stage. The five-year relative survival rate for patients at the metastatic stage is 6.6%.

Zolbetuximab is first-in-class monoclonal antibody that targets and binds to Claudin 18.2 (CLDN18.2), a transmembrane protein. Transmembrane proteins are involved in signal transduction, transport, and protein trafficking, and a study published last year indicated these proteins may contribute to the spread of cancer. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells, which then induces cancer cell death by activating two distinct immune system pathways.

Related: FDA Sets Action Date for Zolbetuximab for Stomach Cancers

Astella’s application is based on results from the phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared with placebo plus mFOLFOX6. The GLOW study evaluated zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared with placebo plus CAPOX.

Results from SPOTLIGHT were published in The Lancet in April 2023. Data from the GLOW study were presented at the March 2023 American Society of Clinical Oncology.

Regulatory applications for zolbetuximab are also under review in several other countries and regions, including Japan, Europe, and China.

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