Astellas refiles CLDN 18.2 cancer drug after FDA knockback

The US FDA has started a fresh review of Astellas' zolbetuximab, trying to become the first claudin (CLDN) 18.2-targeting drug to reach the US market, after turning it down earlier this year.

The FDA sent the Japanese pharma a complete response letter (CRL) in January saying it was unable to approve zolbetuximab as a first-line treatment for CLDN 18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma because of issues raised during an inspection of a contract manufacturer.

The refiling sets the clock ticking on a new six-month appraisal of the antibody, which has priority review status, with a decision now due by 9th November. The drug has already been approved in Japan as Vyloy and is also under review in other areas of the world, including Europe.

In the GLOW and SPOTLIGHT trials, zolbetuximab was to shown reduce the risk of disease progression or death when added to chemotherapy in treatment-naïve patients with this type of cancer and also extended overall survival (OS).

The prospect of a therapy with a brand new mechanism of action has been welcomed in gastric and GEJ cancer, where there has been little in the way of therapeutic innovation in recent decades, despite being the fourth deadliest cancer worldwide, killing around 770,000 people a year. The five-year relative survival rate for patients with metastatic disease is just 7%.

“Those living with advanced gastric or GEJ cancer often face great unmet needs, and the FDA acknowledgement of the zolbetuximab […] resubmission brings us one step closer to offering this important treatment option to eligible patients in the US facing this deadly disease,” said Astellas' head of immuno-oncology development, Moitreyee Chatterjee-Kishore.

Zolbetuximab is at the front of a long list of therapies for CLDN18.2-expressing cancers in clinical development, using a range of therapeutic modalities, and Astellas is also developing a bispecific antibody against the target.

At the ASCO congress, which gets underway today, LaNova is scheduled to report phase 1/2 results with its antibody-drug conjugate (ADC) LM-301 in gastric/GEJ cancer, while FutureGen will present results from a phase 1b study of antibody-based FG-M108 in pancreatic cancer.

Triumvira, meanwhile, has phase 1/2 data comparing up with its autologous T-cell therapy TAC01-CLDN18.2 in solid tumours, and AstraZeneca and Antengene will both report phase 1 data for their ADC candidates, respectively AZD0901 and ATG-022.

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.