FDA puts up CAR-T roadblock, slapping holds on 3 CARsgen cell therapies after inspecting facility

The FDA has put three CAR-T cell therapy candidates from CARsgen Therapeutics on clinical hold after paying a visit to its manufacturing facility, setting back the development of an asset that caught the eye of Moderna and a key enabler of the Chinese biotech’s global expansion plan.

CARsgen started (PDF) clinical manufacturing at the North Carolina facility targeted by the FDA early last year and released its first batch 15 months ago. Things appeared to be progressing according to plan, with the biotech telling investors that the site was “under full operation” and “overall manufacturing operational efficiency improved” in a corporate presentation (PDF) released at the start of this month.

But the FDA reset the narrative this week by putting three CAR-Ts on hold until the findings of its inspection of the facility are resolved. CARsgen said it will “conduct a comprehensive review and improvement on the current good manufacturing practice” but its notice (PDF) lacks details of what the inspectors found. 

It is also unclear how long it will take the biotech to resolve the manufacturing findings and get the hold lifted. Investors see the hold as a significant setback and sent CARsgen’s share price down 30% to 6.57 Hong Kong dollars after the news broke.

The reaction reflects the potential for the setback to harm CARsgen’s chances of carving out a nook in the highly competitive spaces targeted by its CAR-Ts. The three cell therapies affected by the hold target BCMA, Claudin18.2 and GPRC5D, receptors that are priorities for a flock of leading drug developers.  

CARsgen moved its BCMA candidate into a phase 1b/2 multiple myeloma clinical trial at sites in the U.S. and Canada in 2019. ClinicalTrials.gov lists the primary completion date as the end of next year but that estimate was provided before the FDA hold. CARsgen has already given a head start to the approved BCMA CAR-Ts, Johnson & Johnson’s Carvykti and Bristol Myers Squibb’s Abecma.

The Claudin18.2 candidate, CT041, is also in phase 1b/2 and is the subject of a clinical collaboration with Moderna. CARsgen sees CT041 as a potential first-in-class CAR-T but, while it gained an early lead over other cell therapies, it is surrounded by companies that are applying different modalities to the target. The third CAR-T, CT071, targets GPRC5D, a receptor that AstraZeneca, BMS, J&J and Roche are pursuing. 

CARsgen opened the facility in North Carolina to go toe-to-toe with such companies outside its native China, identifying the site as a way to treat 700 patients a year and support clinical trials and early launch activities in North America and Europe.