Capricor Therapeutics has announced positive three-year data from its Phase II open-label extension (OLE) study of deramiocel (CAP-1002) for the treatment of Duchenne muscular dystrophy (DMD), revealing a 47% slowing of disease progression in skeletal muscle. The study also demonstrated enhanced cardiac function, especially among patients with initially higher ejection fractions. These findings support early intervention to potentially impede the progression of cardiomyopathy, a leading cause of mortality in DMD patients. Capricor is scheduled to meet with the FDA in Q3 2024 to discuss the biologics license application (BLA) filing, with topline data from an ongoing Phase III pivotal investigation anticipated in Q4 2024.
Sustained Skeletal and Cardiac Benefits
The Phase II open-label extension study (NCT03406780) followed 12 patients treated with deramiocel over three years. Results indicated a statistically significant benefit in the Performance of the Upper Limb (PUL v2.0) total score, with a 3.7-point difference (p<0.001) compared to an external comparator dataset of similar DMD patients. Cardiac function, measured by magnetic resonance imaging (cMRI), showed improvements in left ventricular ejection fraction (LVEF), left ventricular end systolic volume (LVESV), and left ventricular end diastolic volume (LVEDV).
Dr. Linda Marbán, CEO of Capricor, stated, "The results of the open label study are tremendously important for DMD patients, as they showed sustained skeletal and cardiac benefits after 3 years of continuous treatment with deramiocel, which underscores the potential long-term benefits this therapy can offer patients with DMD."
Safety Profile and Adverse Events
All patients in the study experienced adverse events (AEs), with the majority being low grade. Specifically, 38.5% of events were Grade 3, and no Grade 4 or Grade 5 events were reported. This safety profile aligns with previous deramiocel investigations, supporting its long-term tolerability.
Regulatory and Clinical Development
Capricor plans to discuss options with the FDA to expedite the BLA filing for deramiocel. The company is currently investigating deramiocel in a Phase III pivotal study (NCT05126758), with topline data expected in Q4 2024. A pre-BLA meeting with the FDA has been scheduled for Q3 2024 to finalize filing plans and discuss options for expediting the BLA submission.
Duchenne Muscular Dystrophy Landscape
DMD is a devastating genetic disorder affecting approximately one in every 3,500 male births, characterized by progressive weakness and chronic inflammation of skeletal, heart, and respiratory muscles. The median age of mortality is approximately 30 years. The pathophysiology of DMD involves impaired production of functional dystrophin, leading to muscle cell damage and fibrotic replacement. While Sarepta has secured a label expansion for its DMD therapy Elevidys, there are currently no approved treatments specifically for DMD cardiomyopathy, underscoring the critical need for new therapies.
Mechanism of Action
Deramiocel is a cell therapy utilizing allogeneic cardiac-derived cells from donated healthy human hearts. These cells act by decreasing infarct size in myocardial infarction and ischemic left ventricular dysfunction. The therapy aims to improve muscle strength and cardiac health in DMD patients through immunomodulatory, antifibrotic, and regenerative actions.
