Astellas' gastric cancer candidate rejected by FDA because of manufacturing issues

Two successful phase 3 trials put Astellas’ monoclonal antibody zolbetuximab on track to become the first approved therapy to treat one of the hottest targets in oncology—tumors that are claudin (CLDN) positive.

But the Japanese company will have to clear up manufacturing issues first.

The FDA has sent a complete response letter to Astellas, rejecting zolbetuximab because of unresolved deficiencies identified in a pre-license inspection of a third-party manufacturing facility, the company said. The U.S. regulator granted zolbetuximab priority review in July of last year and established a decision date of Jan. 12.

The application is for locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive.

The FDA raised no concerns about the clinical data for zolbetuximab and is not requesting a new study, Astellas said. The company added that the delay would have limited impact on financial results for the fiscal year ending on March 31 of this year.

“We remain confident in zolbetuximab’s clinical profile and potential to fill a significant therapeutic gap,” Moitreyee Chatterjee-Kishore, Ph.D., Astellas’ chief of immuno-oncology development, said in a release.

Astellas gained zolbetuximab in a $1.4 billion purchase of Ganymed Pharmaceuticals in 2016. In the SPOTLIGHT trial, zolbetuximab improved progression-free survival (PFS) in a genetically defined population of gastric and gastroesophageal junction cancer patients.

Then in March of last year, Astellas revealed that in the GLOW trial, which combined zolbetuximab with a chemotherapy regimen, it improved PFS and overall survival.

Other companies investigating treatments to combat CLDN 18.2 include AstraZeneca, Leap Therapeutics, BioNTech and Legend.