DMD Community Eyes First Cell Therapy Approval Following FDA’s Acceptance of Deramiocel Submission

Linda Marbán, PhD

The FDA has accepted Capricor Therapeutics’ biologics license application (BLA) for deramiocel, as a potential therapy for Duchenne muscular dystrophy (DMD) cardiomyopathy. The agency has scheduled a PDUFA date of August 31, 2025, and if approved, it would become the first cell-based treatment for DMD and the first official treatment for DMD cardiomyopathy.¹

Deramiocel, also referred to as CAP-1002, consists of allogeneic cardiosphere-derived cells (CDCs), a population of stromal cells that exert potent immunomodulatory, antifibrotic, and regenerative actions in dystrophinopathy and heart failure. The therapy’s BLA submission was backed by cardiac data from the phase 2 HOPE-2 trial (NCT03406780) and its open-label extension (OLE), which compared natural history data from an FDA-funded dataset of DMD cardiomyopathy.

The HOPE-2 trial, conducted from 2018 to 2020 with 26 enrolled patients, had its initial findings published in The Lancet in 2022. Of the participants, 8 were randomized to receive deramiocel, 12 to placebo, and 6 were excluded due to screening failure. Among those with post-treatment PUL1.2 assessments, deramiocel demonstrated a significant advantage over placebo in the 12-month mean change from baseline in mid-level elbow PUL1.2 scores (percentile difference: 36.2%; 95% CI: 12.7–59.7; mean difference: 2.6 points; P = .014).²

"We are thrilled to announce the acceptance of our BLA bringing us one step closer to providing this first-in-class treatment for Duchenne-cardiomyopathy, a condition for which there are no approved therapies," Linda Marbán, PhD, chief executive officer at Capricor, said in a statement.¹ "If our application is successful, we expect deramiocel to be a lifelong treatment, administered quarterly, with the potential to be widely adopted across the DMD-cardiomyopathy treatment landscape. We want to extend our appreciation to the patients, their families and advocates who continue to work with Capricor and to the FDA for its commitment to accelerating treatments for DMD."

While there are no approved therapeutics for DMD cardiomyopathy, the condition has historically been managed with a combination of pharmacological and non-pharmacological interventions aimed at preserving cardiac function and delaying progression. These include angiotensin-converting enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists, diuretics, cardiac monitoring, corticosteroids, and device therapy such as implantable cardioverter-defibrillators or cardiac resynchronization therapy.

Craig McDonald, MD

"Deramiocel has shown in multiple clinical trials attenuation of DMD-cardiomyopathy, which is currently one of the leading causes of death in those with DMD," Craig McDonald, MD, professor and chair of the Department of Physical Medicine and Rehabilitation, University of California, said in a statement.¹ "Based on the totality of the safety and efficacy data deramiocel has shown, this potential approval offers patients a first-in-class therapeutic for DMD-cardiomyopathy."

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In the HOPE-2 trial, deramiocel was generally well tolerated in patients with severe DMD, with hypersensitivity reactions as the primary adverse event. To address this, a pretreatment regimen of glucocorticoids, an H1 blocker, and an H2 blocker was implemented, effectively preventing serious allergic reactions. Patients receiving deramiocel demonstrated a significant reduction in creatine kinase (CK)-MB as a proportion of total CK over 12 months, indicating reduced cardiac muscle damage. By month 12, CK-MB levels in the placebo group were notably higher than those in the deramiocel group (percentile difference: 29.1%; 95% CI: 4.0–54.2; P = .025).

After the double-blind phase, eligible participants entered an open-label extension (OLE) study, receiving deramiocel infusions every 3 months. At 3 years, those on deramiocel showed a –4.1-point change in performance of upper limb (PUL v2.0) compared with –7.8 points in an external natural history comparator group, yielding a significant delta of +3.7 points (P < .001). Secondary outcomes from 5-year data revealed a +1.2% improvement in left ventricular ejection fraction (LVEF) among treated patients, with a subgroup of those maintaining at least 45% LVEF at HOPE-2's conclusion showing a +3.0% increase in cardiac function. The external comparator PUL data was sourced from Cincinnati Children’s Hospital Medical Center.^3,4

REFERENCES
1. Capricor Therapeutics Announces FDA Acceptance and Priority Review of its Biologics License Application for Deramiocel to Treat Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. March 4, 2025. Accessed March 4, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/305/capricor-therapeutics-announces-fda-acceptance-and-priority
2. McDonald C, Marban E, Hendrix S, et al. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. 2022;399(10329):1049-1058. doi:10.1016/S0140-6736(22)00012-5.
3. Capricor Therapeutics announces long-term benefit of deramiocel (CAP-1002) in both skeletal muscle and cardiac function in the HOPE-2 OLE study in Duchenne muscular dystrophy. News release. June 28, 2024. Accessed March 4, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/284/capricor-therapeutics-announces-long-term-benefit-of
4. 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 March 4, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/255/capricor-therapeutics-announces-positive-24-month-results