Treatment with investigational cell therapy CAP-1002 improved heart and skeletal muscle function, and reduced cardiac scarring in boys and young men with advanced Duchenne muscular dystrophy (DMD) in a Phase 1/2 trial.
Findings also revealed no serious safety issues related to treatment with Capricor Therapeutics’ lead therapy candidate.
The study, “Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial,” was published in the journal Neurology.
The open-label, randomized HOPE-Duchenne study (NCT02485938) included 25 DMD patients (all older than 12 years, with a mean age of 17.8 years) with significant cardiac scarring, more than two-thirds of whom were wheelchair-dependent when they began the trial. Additionally, the participants had severe limitations in shoulder function but milder limitations in upper limb function.
Over the 12 months of the trial, all participants received the standard-of-care for DMD, including oral steroids. Thirteen also received one dose of CAP-1002 (75 million cells) delivered into the heart.
As previously reported, eight of nine patients experienced improvements in their ability to use their arms and hands. This was assessed with the Performance of the Upper Limb test, a measure of upper limb function related to daily living activities. Control patients had no such improvements.
In addition, magnetic resonance imaging (MRI) revealed that treatment with CAP-1002 eased scarring in the myocardium — the cardiac muscle — at both six and 12 months, and improved the heart’s interior wall thickening, which is required for proper blood pumping throughout the body.
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These benefits in cardiac function were particularly noted in the earliest and most severely affected heart regions. Patients on standard-of care alone showed no relevant changes in cardiac scarring or function.
“Intracoronary CAP-1002 in DMD appears safe and demonstrates signals of efficacy on both cardiac and upper limb function for up to 12 months,” the scientists wrote.
“CAP-1002 is the only therapy so far that has shown reduction in myocardium scar and improvement of localized cardiac function in late stage Duchenne associated cardiomyopathy (heart muscle disease), Michael Taylor, MD, PhD, the study’s lead author, said in a press release.
“These findings suggest that CAP-1002 could be an option for older patients who have scarring in the heart as a result of the underlying disease,” said Taylor, who is the director of cardiac MR research at Children’s Healthcare of Atlanta, adding that the improved upper limb strength is important for patients in the later stages of DMD because it helps them maintain independence.
As for assessments of quality of life — using the Pediatric Outcomes Data Collection Instrument — the cell therapy also improved results of the patient-reported global function at three months and of the patient- and parent-reported happiness score at 12 months. Treatment with CAP-1002 further reduced patient-reported worry and improved their communication scores at six and 12 months, assessed with the Pediatric Quality of Life tool.
CAP-1002 is composed of cardiosphere-derived cells from donated tissue. This type of progenitor cell showed potent immunomodulatory activity in preclinical and clinical studies. Unlike conventional stem cells, which are aimed at restoring dystrophin levels — the protein lacking in DMD — Capricor’s engineered cells release tiny vesicles to prevent inflammation and balance the immune response.
In mouse models of DMD, CAP-1002 improved the physical response to exercise, the absolute force in the lower limbs and diaphragm, and decreased scarring in both skeletal and cardiac muscles.
“Capricor’s pre-clinical studies and the HOPE-Duchenne trial provide evidence that CAP-1002 can help preserve skeletal and cardiac muscle function in patients in the advanced stages of [DMD],” said Linda Marbán, PhD, Capricor’s CEO. “Most importantly, we have shown that there is an opportunity for stabilization or even improvement of disease in patients with later stage [DMD], which represents a large proportion of those living with the disease.”
Capricor is evaluating the safety and efficacy of CAP-1002 in the Phase 2 HOPE-2 clinical trial (NCT03406780) in boys and young men (ages 10 years and older) with DMD who have been treated with standard therapies, including glucocorticoids. The participants are receiving either CAP-1002 or a placebo via intravenous (into-the-vein) injection — a simpler route than delivering into the heart, the team noted — every three months for a total of four treatment cycles over one year.
Scientists will assess whether the therapy improves the physical function of DMD patients, including upper limb and finger movements. If a favorable benefits-to-risk ratio is observed, the patients may participate in an extension study. A recent comprehensive multidisciplinary meeting with the U.S. Food and Drug Administration had positive results, according to Capricor.
The FDA has granted orphan drug status, rare pediatric disease designation and regenerative medicine advanced therapy designation to CAP-1002, intended to accelerate the development of this cell therapy for DMD patients.