The FDA has rejected Capricor Therapeutics’ filing for approval of a Duchenne muscular dystrophy (DMD) cell therapy, raising questions about whether the agency's new leadership may be rowing back from some of the flexibility shown by the old regime. Capricor’s share price fell 38% to $7.11 in premarket trading.
FDA officials decided the deramiocel submission fell short of the requirement for substantial evidence of effectiveness and asked to see more clinical data, the biotech said. Capricor’s circuitous route to its first FDA filing means the company may be able to meet the request for additional clinical data quickly.
Capricor started a phase 3 trial in 2022 after meeting with the FDA to discuss the next steps for the program. At that time, the biotech opted against seeking approval on the strength of a phase 2 dataset that was smaller than planned. Capricor rethought its strategy after three years of data from an open-label extension to the phase 2 trial showed sustained improvements in heart function, data that underpinned the just-rejected submission.
The upshot is that Capricor expects to have data from a double-blind, placebo-controlled phase 3 trial of 104 patients in the third quarter. Capricor CEO Linda Marbán, Ph.D., said in a statement that the company believes the phase 3 results, plus existing data, “could support efforts to resolve the questions raised by the FDA for the treatment of cardiomyopathy associated with DMD.”
Marbán said Capricor was surprised by the complete response letter (CRL), adding that the company followed the FDA’s guidance throughout the process. Recent restructuring and layoffs at the FDA mean the people who provided the guidance and ruled on the filing may have been different than those issuing the CRL.
Capricor completed its submission for FDA approval of deramiocel in DMD cardiomyopathy in January. At that time, Nicole Verdun, M.D., was leading the cell and gene therapy office and Peter Marks, M.D., was director of the Center for Biologics Evaluation and Research. Neither Verdun nor Marks are still in their posts.
On a May earnings call, Marbán said Verdun had been working on the deramiocel file since the start of 2024. Five weeks later, the cell and gene therapy chief was reportedly put on administrative leave and escorted out of the agency. Days after Verdun was put on leave, the FDA dropped plans to hold an advisory committee to discuss the deramiocel submission.
The CRL also references gaps in the chemistry, manufacturing and controls part of the filing, Capricor said. The biotech believes it addressed most of the outstanding items in prior communications with the FDA, but the timing of the CRL meant they weren’t reviewed by the agency. The FDA delivered the CRL seven weeks before the Aug. 31 PDUFA date for the filing.