CAP-1002 Improves Muscle, Lung and Heart Function in Young DMD Patients, HOPE-2 Trial Data Show

One-year treatment with CAP-1002, Capricor Therapeutics’ investigational cell therapy for Duchenne muscular dystrophy (DMD) significantly improves respiratory, cardiac and upper limb function in boys and young men at advanced stages of the disease, top-line data from the HOPE-2 clinical trial show.

“I am incredibly pleased with the outcome of the HOPE-2 trial which demonstrated clinically relevant benefits of CAP-1002 which resulted in measurable improvements in upper limb, cardiac and respiratory function,” Craig McDonald, MD, professor at University of California, Davis, and principal investigator of the HOPE-2 trial, said in a press release.

“This is the first clinical trial which shows benefit to patients in advanced stages of DMD for which treatment options are limited,” he said.

Based on these positive results, Capricor requested a meeting with the U.S. Food and Drug Administration (FDA) to discuss next steps with the ultimate goal to obtain approval of CAP-1002 for DMD.

“The data suggest that CAP-1002 could delay the progression of DMD. We are excited to share this data with FDA and discuss next steps towards commercialization,” said Linda Marbán, president and CEO of Capricor.

CAP-1002 is an experimental cell therapy composed of cardiosphere-derived cells (CDCs), a type of heart progenitor cells with the ability to generate mature cardiac cells. Also, CDCs are known to have regenerative, anti-inflammatory, anti-scarring, and immune modulatory properties.

The Capricor-sponsored Phase 2 trial (NCT03406780) was designed to assess the safety and effectiveness of CAP-1002 in 20 boys and young men in advanced stages of DMD who were being treated with steroids.

Patients were assigned randomly to intravenous delivery (into the bloodstream) of either CAP-1002 (150 million cells per infusion, eight patients) or a placebo (12 patients) every three months for one year.

The trial assessed changes in upper limb (shoulder, arm, hand) function using the Performance of the Upper Limb (PUL) 1.2 and 2.0 tool, a clinically validated measure.

Heart function was assessed by analyzing ejection fraction, left ventricular end systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV), considered the “gold standard” parameters for cardiac function.

Ejection fraction refers to how much blood the heart’s left ventricle pumps out with each contraction. LVESV means the volume of blood at the end of contraction. LVEDV before is the amount of blood before contraction.

As in earlier data, final results showed that patients given CAP-1002 experienced statistically meaningful improvements in the PUL 1.2 and 2.0 when compared to the placebo group. In PUL 2.0 — suggested by the FDA to serve as main efficacy goal toward an application for regulatory approval — participants on CAP-1002 showed a difference of 2.4 points over those receiving a placebo.

In line with the natural history of DMD, muscle function in the placebo group continued to decline, but those treated with CAP-1002 either stabilized or improved their muscle function throughout the one-year treatment.

Participants treated with CAP-1002 also showed significant improvements in cardiac function, as measured by ejection fraction and LVESV.

Researchers saw a significant decrease in the percentage of creatine knase-MB (CK-MB), a marker of cardiac muscle damage, in patients treated with CAP-1002, compared to the controls.

The HOPE-2 trial is the first study to show a correlation between stabilized cardiac function and a decrease in a marker of cell damage, Capricor said.

CAP-1002 was found safe and well-tolerated. The only identified safety signals were hypersensitivity reactions to the injections, which were eased with a common pre-medication regimen.

“To date, there are no therapies to treat the cardiomyopathy [heart disease] associated with DMD,” said Marbán. “Based on the statistically and clinically meaningful improvements in these and other measures of skeletal, cardiac and respiratory performance, we have requested an End-of-Phase 2 meeting with FDA to discuss next steps and a pathway to approval of a Biologics License Application for CAP-1002 in DMD.”

CAP-1002 has been granted regenerative medicine advanced therapy (RMAT), orphan drug and rare pediatric disease designations by the FDA.

If CAP-1002 receives marketing approval from the FDA, Capricor will be eligible to receive a priority review voucher, which would allow the company to expedite the review of its other treatment candidates.

“We have had tremendous support from the DMD advocacy community and we are grateful to the patients and families who participated in this study so that we could reveal the impact of CAP-1002 in treating DMD,” Marbán said.

A webcast discussing HOPE-2 results is available here. Slides presented in that discussion may be seen here.