Capricor Therapeutics reported positive, one-year results from its HOPE-2 phase 2, open label extension study of its experimental therapy CAP-1002 in non-ambulant patients with later-stage Duchenne muscular dystrophy.
Photo: Linda Marbán, CEO of Capricor
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive weakness and chronic inflammation of the skeletal, heart, and respiratory muscles. Patients suffering from DMD typically lose their ability to walk in their teenage years and generally die of cardiac or respiratory complications by age 30. Treatment options are limited, and there is no cure.
CAP-1002 consists of allogeneic cardiosphere-derived cells, or CDCs, a type of progenitor cell that has been shown in pre-clinical and clinical studies to exert potent immunomodulatory activity and is being investigated for its potential to modify the immune system’s activity to encourage cellular regeneration. CDCs have been the subject of more than 100 peer-reviewed scientific publications and have been administered to more than 200 human patients across several clinical studies.
HOPE-2 was a randomized, double-blind, placebo-controlled, phase 2 clinical study of the company’s lead investigational therapy, CAP-1002, in boys and young men who have DMD and are non-ambulant, the later stage of the disease process. Study patients were treated via intravenous delivery with either CAP-1002 (150 million cells per infusion) or placebo every three months. Data from a total of 20 patients was analyzed (12 placebo and 8 treated) at the 12-month time-point and the results were published in The Lancet.
The study met its primary efficacy endpoint, Performance of the Upper Limb (PUL 1.2) scale mid-level dimension, showing a mean 12-month change from baseline in mid-level PUL 1.2, favoring CAP-1002 over placebo (2.6 point difference). Cardiac MRI assessments showed improvements in heart function and structure with CAP-1002 treatment. Left ventricular ejection fraction (LVEF), a global measure of cardiac pump function, decreased significantly in the placebo group over time, but improved in the CAP-1002 group, showing a 107 percent slowing of progression of cardiac disease.
After the completion of the HOPE-2 study, all patients stopped treatment for approximately 392 days, which is referred to as the gap phase. Then all eligible patients who wished to remain on treatment re-entered the open label extension protocol where they received CAP-1002 (150 million cells per infusion) every three months over the course of one year. Patients continued through the gap phase (off treatment for both groups) and the OLE Phase (on treatment for both groups).
Data from the rollover open label extension (OLE) study show statistically significant improvements on the Performance of the Upper Limb (PUL version 2.0) scale for patients on CAP-1002 testing three different hypotheses of treatment benefit during the open label extension. Capricor presented these results at a late-breaking session at this year’s Parent Project Muscular Dystrophy (PPMD) Annual Conference.
In the study, CAP-1002 was made available to all the original 20 patients enrolled in the HOPE-2 study. Of those, 13 entered and 12 completed the first year of study follow-up. As in HOPE-2, CAP-1002 was administered quarterly and current results are from the one-year analysis. The breakdown of patients included seven from the original placebo group and six from the original CAP-1002 treatment group.
CAP-1002 was generally safe and well-tolerated throughout the study, and the safety profile of patients treated in the open label portion of the study is consistent with that seen in previous studies. The HOPE-2 open label extension study remains ongoing, and all participants continue to be monitored for safety and functional performance.
The FDA has granted Capricor’s CAP-1002 RMAT and Orphan Drug Designation, and the company plans to present this data to the FDA and seek additional guidance on the best path forward for DMD patients. Capricor is currently conducting a pivotal phase 3 trial, HOPE-3, designed as a randomized, double-blind, placebo-controlled study with approximately 70 patients and enrollment criteria similar to HOPE-2. The phase 3 study is currently open for enrollment.
“The results from this study are impactful for patients suffering around the world. The open label extension phase of the HOPE-2 study is fairly unique in its design in that all patients were off CAP-1002 or placebo for a mean of approximately one year before resumption or initiation of therapy. These data suggest patients on CAP-1002 accumulate benefit over time where their skeletal muscle function is better preserved which may indicate a long term potential benefit of CAP-1002,” added Linda Marbán, CEO of Capricor. “This evidence builds on the results of the HOPE-2 study, recently published in The Lancet, that showed statistically significant improvements in upper limb function in the treatment group at 12 months.”
Author: Rare Daily Staff
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