Capricor Highlights Two-Year Deramiocel Data as FDA Decision Nears

Key Points

• FDA decision delayed to Nov. 22: The FDA extended the PDUFA date for Capricor’s deramiocel application to review additional two-year open-label data and analyses. The proposed indication has been narrowed to upper-limb impairment in DMD patients older than 9.
• Clinical data showed preserved upper-limb function: In the Phase III HOPE-3 trial, deramiocel produced a 1.1-point advantage over placebo on the PUL 2.0 scale, which investigators described as clinically meaningful. Two-year extension results and pooled analyses continued to show treatment benefits versus placebo and modeled natural-history outcomes.
• Cardiac benefits and manageable safety profile reported: Capricor reported improvements in left ventricular ejection fraction among patients with cardiomyopathy, while adverse events were generally mild and manageable. The company plans to pursue regulatory opportunities outside the U.S. and potentially expand development to younger DMD patients.

Capricor Therapeutics NASDAQ: CAPR presented updated clinical data for deramiocel in Duchenne muscular dystrophy, or DMD, including two-year open-label extension results from its Phase III HOPE-3 study and additional statistical analyses submitted to the U.S. Food and Drug Administration.

Company representatives said the FDA extended the Prescription Drug User Fee Act, or PDUFA, action date for its biologics license application to Nov. 22 to review additional open-label extension data and supportive analyses. Capricor said it would not discuss confidential interactions with the FDA during the presentation.

The company said it was disappointed by the vote of an FDA Advisory Committee but noted that the agency allowed submission of a major amendment. Capricor said its proposed indication has been refined to treatment of upper-limb impairment in patients older than 9 years, rather than an indication focused on DMD cardiomyopathy.

HOPE-3 Upper-Limb Findings

Craig McDonald, National Principal Investigator at the University of California, Davis, said the HOPE-3 trial met its prespecified primary endpoint measuring Performance of the Upper Limb 2.0, or PUL 2.0. The study compared deramiocel with placebo over 12 months in a population that was predominantly non-ambulatory.

According to the presentation, deramiocel produced a 4.55% improvement versus placebo in the prespecified percent-change-from-baseline analysis of PUL 2.0. In a sensitivity analysis based on absolute score changes, the treatment difference was 1.1 points. McDonald said the FDA and investigators in the field have regarded a one-point PUL 2.0 difference as clinically meaningful.

McDonald illustrated the functional relevance of a one-point change with the “bringing hand to mouth” assessment, explaining that patients may move from independently lifting a weighted cup to needing compensatory movements or help from their other arm.

The HOPE-3 open-label extension enrolled 98 participants, with 49 in each original treatment group. Eighty-two patients completed two years of the study. The original placebo group began receiving deramiocel after the first 12 months, while patients initially assigned to deramiocel continued treatment.

McDonald said the delayed-start group showed a 1.56-point difference in upper-limb decline when comparing its placebo year with its subsequent year on deramiocel. Patients treated with deramiocel for both years showed similar rates of decline in the first and second treatment years, according to the presentation.

Capricor also compared open-label extension outcomes with published natural-history data and prognostic models. McDonald said patients receiving deramiocel for two years had a 3.4-point decline in PUL 2.0 compared with a modeled 5.88-point decline. Patients who switched from placebo to deramiocel after 12 months had a 3.76-point decline compared with a modeled 5.35-point decline.

Cardiac Results and Safety

Although Capricor’s current regulatory focus is upper-limb function, the company also presented cardiac MRI data. McDonald said 64 of the 106 HOPE-3 participants had impaired cardiac function at study entry.

In that cardiomyopathy subgroup, Capricor reported a 2.8% treatment effect on left ventricular ejection fraction, or LVEF, at 12 months in the randomized study. In the open-label extension, the company reported a 2.7% treatment effect at 12 months and nearly a 2% effect at 24 months versus external natural-history controls.

Nathaniel Hogan, Capricor’s lead biostatistician, presented a robustness analysis intended to address questions raised during the Advisory Committee meeting about the durability of the statistical findings. Hogan said Capricor ran more than 600 alternative analyses of HOPE-3, varying models, missing-data approaches, included patients and definitions of progression.

“The vast majority of analyses show a treatment benefit at or above one point,” Hogan said, adding that none approached the no-benefit line in the company’s analysis.

Capricor also pooled data from its placebo-controlled HOPE-2 and HOPE-3 studies. The pooled analysis included 62 deramiocel-treated patients and 64 placebo patients with PUL assessments. The company reported a 1.29-point difference favoring deramiocel at 12 months, with a P value of 0.0087.

For cardiac function in the pooled analysis, Hogan reported a 2.2-percentage-point difference in LVEF in the full population at 12 months and a 3.1-point difference among patients with cardiomyopathy at baseline.

McDonald said open-label extension safety data showed adverse effects that were generally mild, short-lived and manageable. Patients receive oral prednisone and antihistamines before infusions to reduce hypersensitivity reactions. He said Capricor has observed no known long-term safety concerns in HOPE-2 and HOPE-3 extension participants followed for as long as five years.

Next Steps

Company representatives said deramiocel is currently administered once every 12 weeks, or four times a year. They said Capricor intends to explore regulatory pathways outside the U.S., including Europe and Japan, and plans to pursue development in younger DMD patients following the FDA decision for the older, largely non-ambulatory population.

Capricor also said it expects deramiocel could be used alongside other DMD therapies, including exon-skipping treatments and potentially gene therapy, while emphasizing that it would continue to monitor safety in combination settings.

About Capricor Therapeutics (NASDAQ:CAPR)

Capricor Therapeutics, Inc is a biotechnology company focused on developing cell and exosome-based therapies for serious diseases. The company's research is based on technologies intended to modulate inflammation, fibrosis and tissue damage, with an emphasis on rare and degenerative conditions.

Capricor's lead investigational product is deramiocel, formerly known as CAP-1002. It is an allogeneic cell therapy derived from cardiosphere-derived cells and is being developed for Duchenne muscular dystrophy, a progressive genetic disorder that causes muscle degeneration.

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