Capricor Formally Submits BLA for Deramiocel in Duchenne Muscular Dystrophy Cardiomyopathy

Linda Marbán, PhD

(Credit: Medium)

Capricor Therapeutics has recently completed the submission of its biologics license application (BLA), seeking full approval for its investigational agent deramiocel as treatment for patients with Duchenne muscular dystrophy (DMD) cardiomyopathy, along with a request for priority review. Completed in late December 2024, the full submission of the rolling BLA was supported by data from the company’s phase 2 HOPE-2 (NCT03406780) and HOPE-2 open label extension (OLE) trials which compared natural history data from a large cohort of patients.¹

HOPE-2, which enrolled originally 26 patients from 2018 to 2020, had original data published in The Lancet in 2022. In total, 8 patients were randomly assigned to deramiocel and 12 patients to placebo, with 6 patients not randomized because of screening failure. Overall, among those who had a post-treatment PUL1.2 assessment, the mean 12-month change from baseline in mid-level elbow PUL1.2 favored deramiocel over placebo (percentile difference, 36.2%; 95% CI, 12.7-59.7; difference, 2.6 points; P = .014).²

“The submission of the BLA marks a pivotal step for Capricor and those impacted by DMD. This BLA is the culmination of a body of work that has been focused on bringing this potentially transformational therapy to those patients in need,” Linda Marbán, PhD, chief executive officer at Capricor, said in a statement.¹ “We believe that the strength of this application is that deramiocel has shown in multiple clinical trials attenuation of the cardiac implications of DMD. We look forward to working with the FDA throughout the review process to support this potential approval.”

In HOPE-2, deramiocel was considered well tolerated in severely affected patients with DMD, with the exception of hypersensitivity reactions. Implementation of a pretreatment procedure with glucocorticoids, an H1 blocker, and an H2 blocker succeeded in preventing serious allergic reactions. Notably, patients on the active therapy showed a marked decrease in creatine kinase (CK)-MB as a proportion of total CK over the course of the study, indicative of reduced cardiac muscle damage. The proportion of CK-MB isozyme at month 12 in the placebo group was increased compared with the deramiocel group (percentile difference, 29.1%; 95% CI, 4.0-54.2; P = .025).

READ MORE: FDA Places Clinical Hold on Phase 2 Study of PGN-EDO51 in Duchenne Muscular Dystrophy

Following the completion of the double-blind, placebo-controlled portion of HOPE-2, eligible participants who wished to remain on treatment entered the OLE where they received deramiocel at 150 million cells per infusion every 3 months. At 3 years from the start of the OLE study, patients with DMD on the active therapy (n = 12) showed a –4.1-point change in performance of upper limb (PUL v2.0), the primary end point, compared with changed of –7.8 for an external natural history comparatory (n = 32; delta change, +3.7 points; P <.001).^3,4

The external comparator PUL data was provided by Cincinnati Children’s Hospital Medical Center. Secondary outcomes, which comprised of 5-year data from the start of HOPE-2, showed a change of +1.2% in left ventricular ejection fraction (LVEF), an end point of cardiac function, for deramiocel-treated patients (n = 10). For those who had at least 45% LVEF at the end of HOPE-2 (n = 8), this subgroup experienced a percent improvement of +3.0%.

All cardiac outcomes were measured using MRI imaging. For the overall deramiocel population, investigators reported improvements of –2.4 mL/m2 and –5.7 mL/m2 for LV end systolic volume and LV end diastolic volume, respectively. Those in the subgroup of deramiocel-treated patients who had at least 45% LVEF at the end of HOPE-2 showed changes of –5.1 and –10.0, respectively. Of note, only 10 of the 12 participants in the study were able to receive MRI.

Deramiocel is the clinical formulation of human allogeneic cardiosphere-derived cells (CDCs). CDCs are a type of stromal or progenitor cell that has been shown in preclinical and clinical studies to exert immunomodulatory, antifibrotic, and regenerative actions in dystrophinopathy and heart failure. HOPE-2 was the first trial of intravenous deramiocel for any indication and the first trial with repeat sequential dosing of cells for a genetic illness.

REFERENCES
1. Capricor Therapeutics Completes Submission of Biologics License Application to the U.S. FDA for Deramiocel for the Treatment of Duchenne Muscular Dystrophy. News Release. Capricor Therapeutics. Published January 2, 2024. Accessed January 2, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/303/capricor-therapeutics-completes-submission-of-biologics
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 January 2, 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 January 2, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/255/capricor-therapeutics-announces-positive-24-month-results