Capricor Therapeutics has announced positive three-year efficacy results from the HOPE-2 open-label extension (OLE) study of CAP-1002 in Duchenne muscular dystrophy (DMD). The data indicate sustained benefits in skeletal muscle and cardiac function, with a favorable safety profile.
The HOPE-2 OLE study evaluated the long-term effects of CAP-1002, an allogeneic cardiac-derived cell therapy, in patients with DMD. The study compared outcomes to an external comparator dataset of similar DMD patients provided by Cincinnati Children’s Hospital Medical Center (CCHMC).
Sustained Improvement in Motor and Cardiac Function
After three years, patients treated with CAP-1002 showed a statistically significant reduction in the decline of upper limb function, as measured by the Performance of the Upper Limb (PUL 2.0) assessment. The CAP-1002 group (n=12) experienced a -4.1 point change from baseline, compared to a -7.8 point change in the external comparator group (n=32), resulting in a +3.7 point difference (p<0.001).
Furthermore, the study observed stabilization in left ventricular ejection fraction (LVEF) in CAP-1002-treated patients, suggesting preservation of cardiac function. According to Capricor’s CEO, Linda Marbán, PhD, the external comparator group showed a steady decline in both skeletal and cardiac function, while CAP-1002 treatment led to sustained disease attenuation.
Regulatory and Clinical Trial Updates
Capricor shared these results with the U.S. Food and Drug Administration (FDA) during a Type-B meeting in May 2024 to support the ongoing HOPE-3 pivotal study. The company anticipates sharing details from the meeting later this month, pending finalization of the meeting minutes. Topline results from the Phase 3 HOPE-3 trial are expected in the fourth quarter of 2024.
About the HOPE-2 and HOPE-3 Trials
The HOPE-2 trial was a randomized, double-blind, placebo-controlled Phase 2 study of CAP-1002 in boys and young men with DMD. Patients were treated intravenously with either CAP-1002 (150 million cells per infusion) or placebo every three months. The HOPE-2-OLE study, an extension of the HOPE-2 trial, continues to monitor participants for safety and functional performance.
The Phase 3 HOPE-3 trial (NCT05126758) is currently underway, evaluating CAP-1002 in approximately 102 boys and young men with DMD, aged 10 and older, who have impaired skeletal muscle function. Participants receive infusions of CAP-1002 (150 million cells per infusion) or placebo every three months for a year. The primary endpoint is the change in upper limb function after one year, assessed using the Performance of the Upper Limb test 2.0 (PUL 2.0).
Duchenne Muscular Dystrophy (DMD) Context
DMD is a genetic disorder characterized by progressive weakness and chronic inflammation of skeletal, heart, and respiratory muscles. It affects approximately one in every 3,500 male births, with an estimated patient population of 15,000-20,000 in the United States. The pathophysiology of DMD involves impaired production of functional dystrophin, leading to muscle cell damage and death. Current treatment options are limited, and there is no cure.
CAP-1002 Mechanism of Action
CAP-1002 is composed of cardiosphere-derived cells (CDCs) sourced from healthy donor heart tissue. These cells promote muscle repair through immunomodulatory, anti-inflammatory, and anti-scarring properties. They release signaling molecules and exosomes that can lower inflammation, stimulate tissue regeneration, and reduce fibrosis.
Regulatory Designations
CAP-1002 has been granted regenerative medicine advanced therapy, orphan drug, and rare pediatric disease designations by the FDA, intended to accelerate its development. Capricor has partnered with Nippon Shinyaku for the exclusive commercialization and distribution of CAP-1002 for DMD in the United States and Japan, pending regulatory approval.
