Capricor Therapeutics is set to file a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for deramiocel, a cell therapy aimed at treating Duchenne muscular dystrophy (DMD) cardiomyopathy. This decision follows productive discussions with the FDA, signaling a significant step forward in addressing a critical unmet need in DMD care. The company plans to complete its rolling BLA submission by the end of 2024.
Clinical Data and Regulatory Pathway
The BLA will leverage existing cardiac data from the Phase 2 HOPE-2 and HOPE-2 Open Label Extension (OLE) trials, juxtaposed with natural history data from Vanderbilt University Medical Center and Cincinnati Children’s Hospital Medical Center. This approach aims to demonstrate deramiocel's efficacy in mitigating cardiac complications associated with DMD.
Linda Marbán, Ph.D., Capricor’s chief executive officer, emphasized the significance of this move, stating, “There are currently no approved therapies for DMD cardiomyopathy, which is the leading cause of death in those with Duchenne. Based on the strength of our cardiac data, combined with the FDA’s commitment to advancing therapeutics for the treatment of rare diseases, we are seeking approval for the cardiomyopathy associated with DMD and will look to expand the label for skeletal muscle myopathy post-approval.”
HOPE-2 and HOPE-2 OLE Trials
Data from the HOPE-2 OLE trial demonstrated long-term benefits of deramiocel in both skeletal muscle and cardiac function. After three years of treatment, patients with DMD on the active therapy (n = 12) showed a –4.1-point change in performance of upper limb (PUL v2.0), compared with changes of –7.8 for an external natural history comparatory (n = 32; delta change, +3.7 points; P <.001).
Secondary outcomes, which comprised of 5-year data from the start of HOPE-2, showed a change of +1.2% in left ventricular ejection fraction (LVEF), an end point of cardiac function, for deramiocel-treated patients (n = 10). For those who had at least 45% LVEF at the end of HOPE-2 (n = 8), this subgroup experienced a percent improvement of +3.0%.
Future Expansion and HOPE-3 Trial
To support potential label expansion for DMD skeletal muscle myopathy, Capricor intends to combine Cohorts A and B of the Phase 3 HOPE-3 clinical trial to serve as a post-approval study. The company does not plan to unblind Cohort A at this time, which was expected in the fourth quarter of 2024.
About Deramiocel
Deramiocel (CAP-1002) consists of allogeneic cardiosphere-derived cells (CDCs), stromal cells with immunomodulatory, antifibrotic, and regenerative actions in dystrophinopathy and heart failure. These cells secrete extracellular vesicles, or exosomes, that modulate macrophage expression, promoting a healing rather than pro-inflammatory phenotype.
Regulatory Designations
Deramiocel has received FDA Orphan Drug Designation, and its regulatory pathway is supported by RMAT (Regenerative Medicine Advanced Therapy Designation). If approved, Capricor would be eligible for a Priority Review Voucher (PRV) based on its rare pediatric disease designation.
