Capricor to Submit BLA for Approval of Dermiocel in Treating DMD Cardiomyopathy
The decision follows positive data from multiple trials, showing significant improvement in both cardiac function and muscle performance in patients with DMD.
Linda Marbán, PhD
Capricor has announced that following recent meetings with the FDA, the company intends to submit a biologics license application (BLA) later this year seeking full approval for its investigational agent deramiocel as a new treatment for patients with Duchenne muscular dystrophy (DMD) cardiomyopathy.1
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 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.1 "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).2,3
READ MORE: FDA Approves Stand-Alone Thearpy Levacetylleucine for Niemann-Pick Disease Type C
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.4 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.
