Capricor Submits BLA for Approval of Dermiocel in Treating DMD Cardiomyopathy

Linda Marbán, PhD

Update, on October 9, 2024, Capricor Therapeutics has announced that the company has initiated its rolling submission process with the FDA for a biologics license application (BLA), seeking full approval for its investigational agent deramiocel as a new treatment for patients with Duchenne muscular dystrophy (DMD) cardiomyopathy. In the recent announcement, the company noted that it plans to complete its rolling BLA submission by the end of 2024.¹

According to the comapny, this application could be eligible for priority review as deramiocel may offer significant improvements in the safety and/or efficacy of treatment for patients with the serious condition of DMD cardiomyopathy, where there are currently no approved treatment options available. Once the rolling BLA submission is fulfilled, the agency will notify Capricor when it is officically accepted for review.

“This announcement marks an important step in the U.S. regulatory process towards a potential Biologics License Application approval of deramiocel for the treatment of DMD,” Linda Marbán, PhD, chief executive officer at Capricor, said in a statement.¹ “An approval of deramiocel would allow us to expedite the delivery of this novel, first-in-class treatment to patients in need. We look forward to working with the FDA during this process.”

On September 25, 2024, Capricor announced that following recent meetings with the FDA, the company intended to submit a BLA later this year seeking full approval for deramiocel to treat patients with DMD cardiomyopathy.² Also known as CAP-1002, the treatment consists of allogeneic cardiosphere-derived cells, a population of stromal cells that have been shown in preclinical and clinical studies to exert potent immunomodulatory, antifibrotic and regenerative actions in dystrophinopathy and heart failure.

In its prior announcement, Capricor claimed it was using data from the phase 2 HOPE-2 (NCT03406780) and HOPE-2 open label extension (OLE) trials as supplementary evidence, as well as combined data from cohorts A and B of the phase 3 HOPE-3 trial (NCT05126758). Notably, the company does not intend to unblind Cohort A from HOPE-3 at this time, which was expected to occur in the fourth quarter of 2024.

"There are currently no approved therapies for DMD cardiomyopathy, which is the leading cause of death in those with Duchenne. Based on the strength of our cardiac data, combined with the FDA’s commitment to advancing therapeutics for the treatment of rare diseases, we are seeking approval for the cardiomyopathy associated with DMD and will look to expand the label for skeletal muscle myopathy post-approval," Linda Marbán, PhD, chief executive officer at Capricor, said in a statement.² "This approach is the result of multiple in-depth meetings with FDA where we showed robust and positive cardiac data from our HOPE-2 and HOPE-2 OLE studies compared to natural history data from a large cohort of patients."

A few months ago, Capricor met with the FDA for a pre-BLA meeting to discuss options to expedite a BLA filing for deramiocel as a treatment for DMD following positive data from the HOPE-2 OLE. 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

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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.

HOPE-3, an ongoing phase 3, double-blind, placebo-controlled study, included 2 cohorts of non-ambulatory and ambulatory boys who are randomly assigned to either deramiocel or placebo every 3 months for a total of 4 doses during the first 12 months of the study. The trial, intended to support regulatory decision, uses PUL v2.0 as the primary outcome, with other various secondary outcomes including cardiac function assessments. Other safety evaluations include adverse events, concomitant medications, physical exam, vital signs, and clinical laboratory testing.

In December 2023, Capricor reported a positive futility analysis of HOPE-3, stating that the data resulted in a favorable recommendation to continue the trial as planned.⁵ At the time of the data readout, the company noted that Cohort A of the trial completed enrollment, with topline data expected to come later this year; however, according to the latest update, that appears to not be happening. Cohort A, which included 58 individuals with DMD and impaired skeletal muscle function, was expected to be a part of the BLA.

REFERENCES
1. Capricor Therapeutics Announces Initiation of Rolling Submission of Biologics License Application (BLA) with U.S. FDA for Deramiocel for the Treatment of Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. October 9, 2024. Accessed October 9, 2024.https://www.capricor.com/investors/news-events/press-releases/detail/293/capricor-therapeutics-announces-initiation-of-rolling
2. Capricor Therapeutics Announces Intent to File Biologics License Application for Full Approval of Deramiocel for the Treatment of Duchenne Muscular Dystrophy Cardiomyopathy. News release. Capricor Therapeutics. September 24, 2024. Accessed September 25, 2024. https://www.capricor.com/investors/news-events/press-releases/detail/291/capricor-therapeutics-announces-intent-to-file-biologics
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 September 25, 2024
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 September 25, 2024. https://www.capricor.com/investors/news-events/press-releases/detail/255/capricor-therapeutics-announces-positive-24-month-results
5. Capricor Therapeutics announces continuation of phase 3 HOPE-3 trial of CAP-1002 in Duchenne muscular dystrophy based on completion of interim futility analysis. News release. December 11, 2023. Accessed September 25, 2024. https://www.capricor.com/investors/news-events/press-releases/detail/267/capricor-therapeutics-announces-continuation-of-phase-3