Capricor Therapeutics has announced alignment with the FDA regarding the design of its HOPE-3 clinical trial, a Phase 3 study evaluating CAP-1002 for the treatment of Duchenne muscular dystrophy (DMD). This agreement establishes a clearer pathway toward a biologics license application (BLA) for CAP-1002, an investigational allogeneic cardiosphere-derived cell therapy. The Type B meeting with the FDA confirmed the trial's key features, including primary endpoints and patient enrollment, potentially expediting the approval process for this therapy aimed at addressing the unmet medical needs of DMD patients.
HOPE-3 Trial Design and Endpoints
The HOPE-3 trial (NCT05126758) is designed to evaluate the efficacy and safety of CAP-1002 in DMD patients. Capricor anticipates enrolling approximately 6 additional patients, bringing the total enrollment to around 58. The trial's primary endpoint, as agreed upon with the FDA, will be the mean change from baseline in the full Performance of the Upper Limb (PUL version 2.0) score, measured 12 months post-treatment. Topline results from the trial are expected in the final quarter of 2024, with a BLA submission planned for 2025. The BLA will be supported by data from cell therapy product manufactured at Capricor’s Los Angeles facility. A separate cohort within HOPE-3 will be treated with product from a San Diego facility to address potential future commercial demand.
Positive Data from HOPE-2 Open-Label Extension
In July, Capricor reported positive 24-month data from the HOPE-2 clinical trial's open-label extension (OLE) study (HOPE-2-OLE; NCT04428476). Among nine patients who completed 24 months of follow-up in the OLE study, six showed improvement in left ventricular ejection fraction (LVEF), as measured by cardiac magnetic resonance imaging, compared to their assessment at the conclusion of HOPE-2. Furthermore, patients demonstrated a statistically significant benefit (P = 0.021) on the PUL version 2.0 scale compared to the rate of decline observed in the placebo group in HOPE-2 at one year of follow-up. These results suggest potential long-term cardiac and skeletal functional benefits of CAP-1002 treatment in DMD.
CAP-1002: A Potential Anchor Therapy for DMD
CAP-1002 consists of allogeneic cardiosphere-derived cells, containing cardiac progenitor cells. It is believed to reduce inflammation and muscle degeneration while promoting muscle regeneration, potentially preserving muscle function for a longer duration in patients. Linda Marbán, PhD, CEO of Capricor, emphasized the importance of these findings, stating that the HOPE-2-OLE data highlights CAP-1002's disease-modifying potential and supports early intervention to prevent irreversible muscle loss. Given its favorable safety and tolerability profile, CAP-1002 is positioned as a potential anchor therapy for DMD patients.
Addressing Unmet Needs in DMD Treatment
While Sarepta Therapeutics' gene therapy, delandistrogene moxeparvovec (Elevidys), has been approved for DMD based on microdystrophin as a surrogate endpoint, the FDA continues to evaluate the validity of this measure for clinical benefit. This ongoing evaluation underscores the need for alternative therapeutic approaches, such as cell therapies like CAP-1002, to address the complex challenges of treating DMD. Capricor's alignment with the FDA on the HOPE-3 trial design represents a significant step forward in the development of CAP-1002 and its potential to improve outcomes for individuals living with DMD.
