In its complete response letter, the FDA cited insufficient evidence establish deramiocel’s effectiveness for cardiomyopathy associated with Duchenne muscular dystrophy. The decision comes after CBER Director Vinay Prasad canceled an advisory committee meeting for the therapy.
The FDA has turned down Capricor Therapeutics’ investigational cell therapy deramiocel for the treatment of cardiomyopathy associated with Duchenne muscular dystrophy, pointing to a lack of supporting evidence for the candidate.
Capricor was down 40% before the opening bell on Friday, trading at $6.79 per share, a significant drop from its $11.40 at the previous market close.
In its complete response letter (CRL), the FDA flagged Capricor’s data package for deramiocel, saying it fell short of the “statutory requirement for substantial evidence of effectiveness,” according to the biotech’s news release on Friday.
Capricor and deramiocel have been at the center of a recent internal FDA clash. Nicole Verdun, the former top regulator of cell and gene therapies at the FDA’s Center for Biologics Evaluation and Research (CBER), had scheduled an advisory committee meeting to discuss deramiocel, as per reporting from STAT News last month. CBER head Vinay Prasad unilaterally canceled that meeting, according to an individual familiar with the matter, STAT said. Verdun and her deputy Rachael Anatol were both pushed out of agency.
The FDA’s decision came down early, as deramiocel’s PDUFA date was set for Aug. 30, after being granted priority review in March. The regulator has requested additional data for deramiocel and has given Capricor the opportunity to request a meeting to discuss a way forward for the cell therapy.
The CRL also cited certain deficiencies regarding deramiocel’s Chemistry, Manufacturing, and Controls. Capricor claimed in its press release that it has already addressed these concerns in previous communications, but the FDA was not able to review these submissions “due to the timing of the CRL issuance.”
In a prepared statement on Friday, Capricor CEO Linda Marbán said the company is “surprised” by the rejection. “We have followed their guidance throughout the process,” she said, noting that aside from the CRL, the review of deramiocel “had advanced without major issues, including a pre-licensure inspection and completion of the mid-cycle review.”
Capricor plans to resubmit its application for deramiocel, backed by upcoming additional findings from the Phase III HOPE-3 trial. Data from this trial are expected in the third quarter.
Deramiocel is composed of allogeneic cardiosphere-derived cells (CDC)—a rare subset of cells in the heart that have been shown to reduce fibrosis and modulate the immune response—which produces healing activity in macrophages, differing from their usual inflammatory behavior. According to Capricor, CDC cells can help preserve cardiac and skeletal muscle.
Capricor is proposing to use deramiocel to treat cardiomyopathy in Duchenne muscular dystrophy (DMD). The biotech’s application was backed by data from the Phase II HOPE-2 study, which in 2020 showed significant improvements in upper-limb strength and performance in patients treated with the cell therapy.
Open-label extension data published in June 2024 demonstrated that deramiocel could maintain these upper-limb beyond 3 years of treatment. At this time point, the cell therapy also stabilized left ventricular ejection fraction, indicating it can preserve heart function in DMD patients.
Friday’s rejection delivers another blow to the embattled DMD space. Last month, the FDA rejected another experimental therapy: Edgewise Therapeutics’ skeletal myosin blocker sevasemten. As in the case of Capricor, the regulator found Edgewise’s data package “insufficient.”
A few days prior, Sarepta Therapeutics reported that a second patient taking its approved DMD therapy Elevidys had died. The deaths—the first one was documented in March—have been linked to acute liver failure, a known side effect of adeno-associated virus-based gene therapies.
