FDA Cites Manufacturing Concerns in Missed Gastric Cancer Drug Deadline

The FDA will not be approving zolbetuximab for some with gastric cancer by the expected deadline, as manufacturing concerns persist.

The Food and Drug Administration (FDA) will not be meeting the deadline for their approval decision on zolbetuximab for the treatment of patients with unresectable (unable to be removed via surgery) or metastatic (spread to other parts of the body) HER2-negative, CLDN 18.2-positive gastric or gastroesophageal junction adenocarcinoma, according to a statement by Astellas, the manufacturer of the novel drug.

The FDA set a decision deadline of Jan. 12, 2024, per the Prescription Drug User Fee Act.However, on Jan. 4, the agency sent a complete response letter to Astellas stating that they cannot approve zolbetuximab by Jan. 12, due to “unresolved deficiencies following its pre-license inspection of a third-party manufacturing facility,” the release stated.

Of note, the FDA did not cite any clinical concerns about zolbetuximab, including safety and efficacy (how well the drug works to treat cancer). The agency is not requesting additional clinical studies be conducted.

“We remain confident in zolbetuximab’s clinical profile and potential to fill a significant therapeutic gap for those diagnosed with advanced gastric or GEJ cancer whose tumors are CLDN18.2 positive,” Moitreyee Chatterjee-Kishore, senior vice president and head of immuno-oncology development at Astellas said in the release.

Zolbetuximab is a monoclonal antibody that targets and attaches to CLDN 18.2, a protein that has abnormal overexpression in the cells of certain gastric cancers. The press release explained that according to findings from preclinical studies (meaning that the trials were not done in humans), once zolbetuximab binds to the cancer cells, it induces cell death.

In January of last year, Dr. Kohei Shitara, a medical oncologist at National Cancer Center Hospital East in Japan, said that “Zolbetuximab plus mFOLFOX6 is a potential standard-of-care treatment for a biomarker-based subgroup of patients with CLDN18.2-positive/HER2-negative locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.”

Shitara was the lead study author on the phase 3 SPOTLIGHT clinical trial, which evaluated zolbetuximab plus mFOLFOX6 (a chemotherapy combination) in this patient population. Findings showed that zolbetuximab plus mFOLFOX led to improved overall survival (time a patient lives during and after treatment) and progression-free survival (time from treatment until disease worsening or death) compared to those who received a placebo plus mFOLFOX.

Later, in July 2023, the FDA granted a priority review for a biologics license application to zolbetuximab, based on findings from the SPOTLIGHT trial, as well as findings from the GLOW clinical trial, which compared zolbetuximab plus CAPOX (oxliplatin and capecitabine) to placebo plus CAPOX. Once again, study findings showed that patients who received the zolbetuximab-containing regimen tended to have superior overall and progression-free survival.

READ MORE:FDA Accepts Application for Zolbetuximab in Gastric, GEJ Cancers

A priority review is granted to drugs that show promise in treating severe illnesses or conditions. By granting a priority review, the FDA agrees to work with the drug developers to speed up the review and potential approval of the therapy, so it was at this point that the Jan. 12 decision date was established.

According to the press release, Astellas is “working closely with the FDA and the third-party manufacturer to establish a timeline to quickly resolve the agency’s feedback,” according to the release.

“Astellas is committed to working with the FDA and the third-party manufacturer to address the agency’s feedback, and to bringing zolbetuximab to U.S. patients in need, as soon as possible,” Moitreyee said.

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