Cell Therapy Deramiocel Meets Primary End Point in Phase 3 DMD Cardiomyopathy Trial

Positive topline data from Capricor Therapeutics’ phase 3 HOPE-3 trial (NCT05126758) of deramiocel showed that the investigational cell therapy met its primary end point in slowing disease progression among patients with Duchenne muscular dystrophy (DMD) cardiomyopathy. The company noted that, following prior alignment with the FDA, it plans to submit its response to the agency’s recent complete response letter (CRL), incorporating the new HOPE-3 data to support deramiocel.¹

Topline results demonstrated that treatment with deramiocel significantly delayed disease progression compared with placebo on the primary end point of Performance of Upper Limb (PUL v2.0) total score, showing a 54% slowing of progression in the intent-to-treat population (ITT) at 12 months (n = 105; P = .029). For the key secondary end point, left ventricular ejection fraction (LVEF%), deramiocel was associated with a 91% slowing of decline based on centrally reviewed cardiac MRI evaluations in the ITT population across 12 months (n = 83; P = .041). Notably, the company observed that the safety and tolerability of deramiocel were consistent with prior studies.

"We believe the HOPE-3 PUL results show statistically and clinically meaningful and significant treatment effects on both upper limb function and cardiomyopathy," principal investigator Craig McDonald, MD, distinguished professor of physical medicine and rehabilitation and pediatrics at UC Davis Health, said in a statement.¹ "A nearly 54 percent slowing of skeletal muscle disease progression is extraordinary in Duchenne and directly linked to maintaining independence and quality of life in the most severely affected patients with greatest unmet need."

"The preservation of function reflected in PUL v2.0 translates into real, practical benefits for boys and young men living with this disease, and the effect of Deramiocel on cardiomyopathy will potentially translate to improved long-term survival. The HOPE-3 study is the first-ever Phase 3 trial in a largely non-ambulatory population with DMD to successfully meet its primary endpoint and to support the development of an innovative therapy over many years with this level of impact has been a profound privilege," McDonald added in a statement.¹

HOPE-3 is a randomized, double-blind, placebo-controlled, phase 3 trial testing deramiocel in boys and young men living with DMD across 20 sites in the United States. In the trial, participants received intravenous deramiocel at 150 million cells per infusion or placebo every 3 months for 12 months. Overall, the mean age of participants was approximately 15 years, and all were on a stable corticosteroid regimen during the trial. Baseline demographics were well balanced between treatment arms; approximately 90% were receiving cardiac medications at baseline, and over 75% of patients had a clinical diagnosis of cardiomyopathy.

“The cardiac findings from HOPE-3 represent a significant advance in the management of Duchenne muscular dystrophy cardiomyopathy,” Jonathan Soslow, MD, MSCI, professor of pediatrics (cardiology) at Vanderbilt University Medical Center, said in a statement.¹ “Cardiomyopathy is the leading cause of mortality in Duchenne, and stabilizing cardiac function has remained a major unmet need. The statistically and clinically significant preservation of left ventricular ejection fraction in patients treated with Deramiocel observed in HOPE-3 underscores the potential of Deramiocel to address one of the most critical aspects of the disease.”

READ MORE: FDA Adds Boxed Warning, Narrows Indication for DMD Gene Therapy

In July 2025, the FDA issued Capricor the CRL for deramiocel, stating that it was unable to review the biologics license application (BLA) in its current form because it did not meet the requirements for substantial evidence of efficacy.² In addition, the agency noted outstanding items in the Chemistry, Manufacturing, and Controls section of the application, most of which the company stated it believed had been addressed in prior communications with the FDA. For context, the BLA submission for deramiocel was based on data from the HOPE-2 trial (NCT03406780), its open-label extension, and natural history comparisons from FDA-funded datasets.

HOPE-2 enrolled 26 patients, 8 who were randomized to deramiocel, 12 to placebo, and 6 who were excluded due to screening failure. All told, deramiocel-treated patients showed a statistically significant 36.2% improvement over placebo in 12-month mid-level elbow PUL1.2 scores (mean difference, 2.6 points; 95% CI, 12.7-59.7; P = .014). Treatment with the cell therapy led to significant reductions in creatine kinase (CK-MB) as a proportion of total CK over 12 months, indicating less cardiac muscle damage, with a 29.1% difference vs placebo (95% CI, 4.0-54.2; P = .025).³

"HOPE-3 delivered strong and definitive evidence that Deramiocel can meaningfully improve the course of Duchenne muscular dystrophy, demonstrating statistically significant improvements in both skeletal and cardiac function,” Linda Marbán, PhD, chief executive officer at Capricor, said in a statement.¹ “These results reinforce the durable benefits seen in HOPE-2 and its open-label extension, which has continued for over 48 months, and highlight the strength, consistency, and reproducibility of Deramiocel’s clinical profile after more than a decade of rigorous clinical development."

"We believe these pivotal study results, in addition to the evidence from the HOPE-2 and HOPE-2 OLE studies, position us to address the clinical issues in the Complete Response Letter received earlier this year, consistent with prior FDA guidance that HOPE-3 results should be sufficient to support regulatory approval," Marbán added in the statement.¹ "For families living with Duchenne who are looking for therapies that preserve functional ability, protect the heart and maintain independence, today’s results provide real momentum and meaningful progress, offering renewed confidence as we work to advance Deramiocel toward potential regulatory approval."

REFERENCES
1. Capricor Therapeutics Announces Positive Topline Results from Pivotal Phase 3 HOPE-3 Study of Deramiocel in Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. December 3, 2025. Accessed December 10, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/331/capricor-therapeutics-announces-positive-topline-results
2. Capricor Therapeutics Provides Regulatory Update on Deramiocel BLA for Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. July 11, 2025. Accessed December 10, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/319/capricor-therapeutics-provides-regulatory-update-on
3. 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.