FDA Controversy Surrounds Capricor's Deramiocel for DMD Cardiomyopathy

In a surprising turn of events, Capricor Therapeutics finds itself at the center of a regulatory storm as it fights to secure approval for deramiocel, its investigational cell therapy for cardiomyopathy associated with Duchenne muscular dystrophy (DMD). The company's journey has been marked by unexpected setbacks, internal FDA conflicts, and a renewed push for approval based on existing data.

Complete Response Letter and FDA Leadership Shake-up

Capricor received a complete response letter (CRL) from the FDA last month for deramiocel, a rejection that CEO Linda Marbán described as "unexpected" given the company's positive interactions with the agency throughout the review process. The situation was further complicated by the sudden departure and subsequent return of Dr. Vinay Prasad as head of the Center for Biologics Evaluation and Research (CBER) at the FDA.

Marbán expressed surprise at Prasad's return, noting, "It was pretty clear that he was asked to leave... But I think what it showed is that [FDA Commissioner Marty] Makary has tremendous faith in him." This leadership shake-up has added another layer of complexity to Capricor's regulatory strategy.

Regulatory Path and Clinical Data

Capricor plans to resubmit its Biologics License Application (BLA) based on deramiocel's existing dataset. The company's regulatory path has been built on FDA guidance for defining efficacy in the DMD patient population. Key data supporting the application include:

• Results from the Phase II HOPE-2 trial, published in May 2020, showing significant improvements in upper-limb strength and performance.
• Open-label extension (OLE) data published in June 2024, demonstrating maintenance of upper limb benefits beyond three years of treatment and stabilization of left ventricular ejection fraction (LVEF).

Dr. Craig McDonald, lead investigator on Capricor's trials, emphasized the importance of these findings, stating, "It was certainly the feeling by Capricor physician scientists in the space that this was really the first therapeutic that's really been shown to stabilize the cardiomyopathy."

Shifting Endpoints and Future Plans

In response to recent developments, Capricor has submitted a protocol amendment to designate LVEF as the primary efficacy endpoint for its ongoing Phase III HOPE-3 trial, with upper limb performance as a pre-specified secondary endpoint. This change is based on multiple factors, including the objectivity of LVEF measurements and recent research elucidating its relevance to DMD cardiomyopathy.

Marbán outlined several potential paths to approval during a recent Type A meeting with the FDA, prioritizing "the continued review of our previously filed BLA, which we believe meets the applicable regulatory requirements for approval." The company expects to receive minutes from this meeting by mid-September, which Marbán hopes will provide "at least a roadmap forward."

As the pharmaceutical industry watches closely, Capricor's experience highlights the complex and often unpredictable nature of the drug approval process, particularly for novel therapies addressing rare and life-threatening conditions.