CAP-1002 demonstrates positive phase 2 results to treat Duchenne muscular dystrophy

Capricor Therapeutics has announced positive phase 2 data for CAP-1002 to treat Duchenne muscular dystrophy (DMD), a genetic disorder causing progressive weakness and chronic inflammation of the skeletal, heart, and respiratory muscles. according to a press release.¹ The positive, 24-month safety and efficacy results were demonstrated in the ongoing HOPE-2 open label extension (OLE) (NCT NCT04428476) study, in which most participants had improvement in left ventricular ejection fraction (LVEF) with 2 years of CAP-1002 treatment.^1,2 These results, according to Capricor Therapeutics, suggest cardiac function preservation.¹

After 2 years of treatment, patients have shown statistically significant benefit in the Performance of the Upper Limb (PUL v2.0) scale compared to the original rate of decline in the placebo group of HOPE-2 (P = 0.021). Previously, HOPE-2-OLE met the primary endpoint at the 1-year timepoint of the PUL v2.0 scale (P = 0.02).¹

The HOPE-2 trial was a placebo-controlled, randomized, and double-blind clinical study of CAP-1002 in boys and young men with DMD aged 10 years and up.^1,2 Of the 20 total participants, 8 were treated with CAP-1002 (150 million cells per infusion) via intravenous delivery or placebo every 3 months. At trial completion, treatment was stopped in all patients for 392 days (gap phase) (mean, range [239, 567]). Thirteen eligible participants that wanted to remain on-treatment re-entered the OLE study, in which they received CAP-1002 every 3 months across 24 months.^1,2

LVEF was measured via cardiac magnetic resonance imaging (cMRI). Improvements in heart function were observed in 6 of 9 patients treated with CAP-1002 relative to their respective final assessment at the conclusion of HOPE-2. An increasing correlation with PUL v2.0 and ejection fraction results were observed over time (24-month OLE results r = 0.75, P = 0.02).¹

CAP-1002 consists of allogeneic cardiosphere-derived cells (CDCs), stromal cells that exert potent immunomodulatory, antifibrotic and regenerative actions in dystrophinopathy and heart failure (demonstrated in preclinical and clinical studies). CDCs, the subject of more than 100 peer-reviewed scientific publications, act by the secretion of extracellular vesicles (exosomes) that target macrophages and alter their expression profile, adopting a healing phenotype, compared to a pro-inflammatory phenotype. Across multiple clinical trials, CDCs have been administered to more than 200 human participants.

Recently, the FDA approved delandistrogene moxeparvovec-rokl (ELEVIDYS; Sarepta Therapeutics, Inc), the first gene therapy to treat ambulatory pediatric patients aged 4 to 5 years. On June 29, 2023, the FDA accepted Italfarmaco Group’s New Drug Application (NDA) for givinostat (ITF2357), a proprietary histone deacetylase (HDAC) inhibitor for DMD treatment, with a Prescription Drug User Fee Act (PDUFA) date set for December 21, 2023.

References:

1. Capricor Therapeutics announces positive 24-month results from ongoing HOPE-2 open label extension study of CAP-1002 in Duchenne muscular dystrophy. Capricor Therapeutics. June 30, 2023. Accessed June 30, 2023.
2. Open-label extension of the HOPE-2 trial. ClinicalTrials.gov. Accessed June 30, 2023. https://clinicaltrials.gov/ct2/show/NCT04428476