CAP-1002 Cell Therapy Improves Arm, Heart Function in DMD
Treatment with the investigational cell therapy CAP-1002 significantly improved arm and heart function in boys and young men at advanced stages of Duchenne muscular dystrophy (DMD), according to final data from the HOPE-2 clinical trial.
The Phase 2 trial also “met various skeletal and cardiac endpoints [goals] suggesting clinically relevant slowing of disease progression,” Capricor Therapeutics, the company developing CAP-1002, said in a press release.
Now, after receiving “clarity” from the U.S. Food and Drug Administration on the next steps in the therapy’s development, Capricor said it’s planning another clinical trial called HOPE-3. If results from HOPE-3 also are positive, they likely will support applications for regulatory approval, the company said.
“The significance of this data is vitally important to patients and the DMD community. The data suggests that CAP-1002 slowed the decline of DMD in patients [with advanced disease] for whom few options currently exist,” said Linda Marbán, PhD, Capricor’s CEO.
“Now that we have clarity from the FDA and based on the strength of this data set, we are poised to embark on the HOPE-3 pivotal trial once we have secured an appropriate partner that can help drive CAP-1002 forward towards commercialization,” Marbán added.
The Capricor-sponsored HOPE-2 trial (NCT03406780) enrolled 20 boys and young men with DMD at nine sites across the U.S. All of the participants had relatively advanced disease, with about 80% unable to walk.
During the study, eight participants received CAP-1002 (at a dose of 150 million cells per infusion), delivered by infusion directly into the bloodstream every three months. The other 12 participants were given placebo infusions. All trial participants were also continually treated with steroids.
The trial’s primary endpoint, or main goal, was to assess the effect of treatment on scores on the Performance of the Upper Limb (PUL) 1.2, a validated test of arm functionality that reflects how easy it is for patients to do various day-to-day tasks.
The results showed that, at the end of the trial, scores on the mid-level PUL 1.2 were significantly higher — by 2.6 points on average — among participants given CAP-1002, compared with those given the placebo. This difference in scores specifically reflects better elbow function among participants given the investigational therapy.
CAP-1002 also led to significant improvements on the overall PUL 1.2 score, which assesses function from the shoulder to the hand. The average score in the CAP-1002 group was 3.2 points higher than in the placebo group.
Treatment also improved heart function. Left ventricle ejection fraction — a measure of how much blood the heart pushes out to the body with each pump — was significantly higher, by 4% on average, in the CAP-1002 group.
The CAP-1002 group also had significant decreases in left ventricular end systolic volume, or LVESV, and left ventricular end-diastolic volume, or LVEDV — the amount of blood in the heart at the end of a contraction and just before a contraction, respectively. Specifically, LVESV was 4.2 mL/square meter (m2) lower in the CAP-1002 group, while LVEDV was 12.4 mL/m2 lower, on average.
Significant reductions following CAP-1002 treatment also were found in creatine kinase-MB, a marker of heart muscle damage, which decreased by 2.2% on average.
“This groundbreaking study is extremely exciting as we saw statistically significant changes of CAP-1002 in both skeletal and cardiac function,” said Craig McDonald, MD, a professor at the University of California at Davis and national principal investigator for the HOPE-2 clinical trial.
“For these older boys who have limited therapeutic options, these data support the belief that CAP-1002 may become an important therapeutic option and possibly slow the progression of DMD,” McDonald said.
The cell therapy was generally safe and well-tolerated throughout the clinical trial. The only serious safety findings were two allergic reactions that occurred early on, and were managed with a common pre-infusion treatment, according to Capricor.
“We are thankful to the patients and families who participated in this study so that we can demonstrate the impact of CAP-1002 in treating DMD,” said Marbán.
CAP-1002 contains cardiosphere-derived cells, a type of early heart cell. It secretes tiny vesicles called exosomes that are taken up by different types of cells in the body to encourage cellular regeneration. The investigational treatment has been granted regenerative medicine advanced therapy, orphan drug, and rare pediatric disease designations by the FDA.
Based on the earlier results of this trial, Capricor had requested a meeting with the FDA to discuss the next steps in the therapy’s development, with the ultimate goal to obtain regulatory approval of CAP-1002 for DMD.