FDA blocks Astellas’ Claudin cancer drug over manufacturing

Manufacturing problems have scuppered Astellas’ chances of approval in the US this month for zolbetuximab, currently leading the field among Claudin 18.2-targeted drug candidates for cancer.

The FDA has sent the Japanese drugmaker a complete response letter (CRL) saying it is unable to approve zolbetuximab as a first-line treatment for Claudin 18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma because of “unresolved deficiencies following its pre-license inspection of a third-party manufacturing facility.”

It’s a disappointing outcome for Astellas, which won an FDA priority review designation for zolbetuximab in July on the back of two phase 3 studies that showed the drug was able to reduce the risk of disease progression or death when added to chemotherapy in treatment-naïve patients with this type of cancer. The regulator had been scheduled to deliver a decision on the application by 12th January.

Astellas said in a statement that the FDA had not raised any issues with clinical data for zolbetuximab, including its efficacy and safety, and is not asking for any additional clinical trials of the drug.

That suggests the delay could be relatively short, assuming the issues at the CMO can be resolved in a timely manner or production switched to a new partner, but it will narrow Astellas’ lead over other companies developing Claudin 18.2-targeted drugs such as Merck KGaA/Hengrui, Innovent, I-Mab, BioNTech, and Legend Biotech.

The company said it is “working closely with the FDA and the third-party manufacturer to establish a timeline to quickly resolve the agency’s feedback,” adding that none of its other products have been affected by the issue.

Astellas acquired zolbetuximab with its takeover of Ganymed Pharma in 2016, paying around $430 million upfront in a deal with a total value of up to $1.3 billion, depending on the antibody meeting development, regulatory, and commercial objectives.

Analysts have suggested that sales could reach $1 billion, assuming of course that Astellas is able to target the approximately one-third of gastric cancer patients with Claudin-18.2-positive tumours effectively. That will require the establishment of a diagnostic framework to test for the biomarker.

Astellas has been working with partner Ventana on companion diagnostics needed to screen for patients who may be eligible for treatment with the drug.

Moitreyee Chatterjee-Kishore, senior vice president and head of immuno-oncology development at Astellas, said: “We remain confident in zolbetuximab’s clinical profile and potential to fill a significant therapeutic gap” for patients with this type of cancer.