FDA Rejects Capricor's DMD Cell Therapy; Company Disputes Efficacy Interpretation

The U.S. Food and Drug Administration (FDA) has rejected Capricor Therapeutics' Duchenne muscular dystrophy (DMD) cell therapy, deramiocel, citing concerns over efficacy data interpretation and trial design. The company has responded, claiming the FDA misinterpreted key efficacy data that led to the rejection.

FDA's Rejection and New Transparency Initiative

The FDA included deramiocel in a new batch of 89 complete response letters (CRLs) publicly released on September 4, 2025, as part of the agency's new initiative to increase transparency in the drug approval process. This move represents a significant shift in FDA policy, with the agency now publishing rejection letters for unapproved drugs simultaneously with their issuance to sponsoring companies.

Capricor's CEO, Linda Marbán, Ph.D., stated, "Transparency is vital in regulatory communications, especially when patients are waiting for therapies with the potential to alter the course of devastating diseases such as Duchenne muscular dystrophy." The company was not notified in advance of the FDA's decision to make the rejection letter public.

Capricor's Response and Data Interpretation

Capricor has publicly released its July 16 response to the FDA's rejection, which was initially issued on July 9. The company's response aims to clarify points identified in the CRL and outlines plans to address remaining concerns.

A key point of contention is the interpretation of the phase 2 HOPE-2 trial results. While the FDA stated that the trial "failed to demonstrate efficacy for its prespecified primary efficacy endpoint," Capricor argues that this endpoint was actually met. The company claims that when analyzed using more appropriate statistical techniques, the primary outcome showed statistical significance with a p-value of 0.014.

Cardiomyopathy Indication and Trial Design

Capricor's application also sought approval for deramiocel to treat DMD-associated cardiomyopathy. The FDA expressed concerns about the "50 secondary and exploratory endpoints" included in the data, which were allegedly not prespecified for hypothesis testing and lacked controls for false positives.

Capricor expressed surprise at these concerns, stating that all endpoints were prespecified and that the company's plans had been extensively discussed with the agency prior to the biologics license application (BLA) submission. The company wrote, "It is difficult to understand the massive change in the agency's feedback provided in the CRL, when the initial plan to use the HOPE-2 and HOPE-2-OLE as the clinical basis for the BLA was set into motion with FDA's agreement just under one year ago."