Cell Therapy CAP-1002 Continues to Show Preservation of Cardiac Function in Open-Label Extension Study of DMD


Building on positive 1-year data, 24-month data showed statistically significant differences in the Performance of the Upper Limb scale in treated patients in the open-label extension relative to those on placebo in the double-blind period.

Linda Marbán, PhD, chief executive officer at Capricor

Linda Marbán, PhD

Newly announced data from the open-label extension (OLE) period of the phase 2 HOPE-2 trial (NCT03406780) showed continued improvement of patients’ left ventricular ejection fraction (LVEF) after 2 years of treatment with CAP-1002 (Capricor), a cell therapy in development for Duchenne muscular dystrophy (DMD).1

Following the double-blind, placebo-controlled period, participants entered the OLE where they received CAP-1002 at 150 million cells per infusion every 3 months over the course of 24 months. In addition to showing improvement in LVEF, which was indicative of cardiac function, treated patients showed statistically significant benefits in Performance of the Upper Limb (PUL v2.0) scale after 2 years in comparison with the original rate of decline from the placebo group at 1 year.

"The results from this two-year open label study are tremendously impactful for DMD patients showing cardiac and skeletal functional benefits, which underscores the potential long-term benefits of CAP-1002 treatment in DMD," Linda Marbán, PhD, chief executive officer at Capricor, said in a statement.1 "Importantly, the natural history of DMD cardiomyopathy suggests a steady decline in cardiac function as measured by ejection fraction, however, in HOPE-2-OLE, we observed improvements in heart function in six of nine patients."

LVEF, measured using cardiac MRI, was improved in 6 of the 9 patients at the end of the HOPE-2 study. Over time, there was an increasing correlation between PUL v2.0 and ejection fraction results (r = 0.75; P = .02). The therapy was well-tolerated with a safety profile that was consistent to previous observations.

"Furthermore, as the HOPE-2-OLE data highlights the disease modifying potential of CAP-1002, we believe it is imperative to start treatment as early as possible to prevent the irreversible loss of muscle," Marbán added.1 "Taken together with the favorable safety/tolerability profile, these data position CAP-1002 as a potential anchor therapy for DMD patients. We thank the patients, their families, caregivers, and the broader Duchenne community for continuing to work with us on this promising therapy."

The newly announced data build upon full findings from the double-blind portion of the trial, which were announced in March 2022. After receiving 4 doses of CAP-1002, data at the 1-year time point revealed a change in PUV 1.2v, the primary end point, that favored the study drug over placebo (difference, 36.2%; 95% CI, 7.9-64.5; difference of 2.6 points; P = .014). This finding represented a clinically significant 71% slowing of loss of function with CAP-1002.2

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The secondary end point of change in midlevel PUL 1.2 at 6 months, was significantly different between groups, favoring CAP-1002 (percent difference, 27.6%; 95% CI, 0.39-54.9; difference of 1.5 points; = .047). At 3 and 9 months, changes also favored CAP-1002 and were clinically meaningful but not statistically significant. The difference at 3 months was 1.2 points (percentile difference, 19.8; 95% CI, –6.5 to 46.1) and 1.5 points at 9 months (percentile difference, 19.6; 95% CI, –8.2 to 47.4). Notably, the secondary outcome of systolic left ventricular wall thickening (septal, lateral, inferior, and anterior) by cardiac MRI did not statistically favor CAP-1002 over placebo.

CAP-1002 is also currently being evaluated in a phase 3 trial called HOPE-3 (NCT05126758), a multicenter, randomized, double-blind, placebo-controlled study of both nonambulatory and ambulatory boys and young men with DMD. Expected to be complete in late June 2024, the trial included an estimated 68 participants who will receive either CAP-1002 or placebo for a 12-month period. The study will use mean change in full upper limb function as measured by PUL v2.0 scores as the primary end point, with changes in cardiac muscle function and structure as secondary outcomes.

"We are encouraged by the robust and consistent results observed to date and will continue to work closely with the U.S. Food and Drug Administration (FDA) to bring CAP-1002 to patients as quickly as possible,” Marbán said in a statement.1 "We plan to discuss these results as well as the key features of our ongoing Phase 3 HOPE-3 trial and outline our proposed path towards submission of a potential Biologics License Application (BLA) during our upcoming meeting with the FDA. In parallel, HOPE-3 continues to enroll patients and we remain on track to complete enrollment in the second half of 2023 and report the interim analysis in the fourth quarter of 2023."

1. Capricor Therapeutics announces positive 24-month results from ongoing HOPE-2 open label extension study of CAP-1002 in Duchenne muscular dystrophy. News release. June 30, 2023. Accessed July 6, 2023. https://www.capricor.com/investors/news-events/press-releases/detail/255/capricor-therapeutics-announces-positive-24-month-results
2. McDonald CM, Marban E, Hendrix S, et al. Repeated intravenous cardiospere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicenter, randomized, double-blind, placebo-controlled, phase 2 trial. Lancet. Published online March 12, 2022. doi:10.1016/S0140-6736(22)00012-5
3. McDonald C. A study of CAP-1002 in ambulatory and non-ambulatory patients with Duchenne muscular dystrophy (HOPE-3). University of California Health. Updated February 3, 2022. Accessed July 6, 2023. https://clinicaltrials.ucbraid.org/trial/NCT05126758
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