Capricor Reports Positive DSMB Review of Phase 3 HOPE-3 Interim Results


The positive data report could potentially build on phase 2 study of Duchenne muscular dystrophy in which CAP-1002 met its primary end point.

Linda Marbán, PhD, chief executive officer, Capricor

Linda Marbán, PhD

Capricor Therapeutics recently reported a positive futility analysis of its phase 3 HOPE-3 study (NCT05126758) assessing its investigational agent CAP-1002 in patients with Duchenne muscular dystrophy (DMD). The results of the interim analysis were conducted by the study’s Data Safety Monitoring Board (DSMB), which resulted in a favorable recommendation to continue the trial as planned.1

Cohort A of the HOPE-3 has completed enrollment, with topline data expected to be announced in the 4th quarter of 2024. The company plans to request a meeting with the FDA in the first quarter of next year to further discuss opportunities for expedited approval pathways. With the successful futility analysis, Capricor is forced to pay its first milestone payment to Nippon Shinyaku as part of its US Commercialization and Distribution Agreement.

"We are pleased with the positive outcome of the DSMB review which supports the continued advancement of our HOPE-3 trial towards potential approval of CAP-1002 for the treatment of DMD," Linda Marbán, PhD, chief executive officer, Capricor, said in a statement.1 "We believe CAP-1002 may address the high unmet medical need for these patients and we remain committed to its expeditious advancement towards approval. Based on this important milestone, we will be requesting a meeting with the U.S. Food and Drug Administration (FDA) to further discuss options for expedited review and approval. In addition, we believe we are well positioned to execute on additional value-driving clinical and regulatory milestones, including reporting topline data from HOPE-3 (Cohort A) in the fourth quarter of 2024."

CAP-1002, an allogenic therapy, consists of off-the-shelf cardiosphere-derived cells (CDCs), which have been the subject or more than 100 peer-reviewed scientific publications since they were discovered in 2007. In CAP-1002, the cells release exosomes that are taken up largely by macrophages and T cells and begin a cycle of repair. To date, the agent has received orphan drug designation and has a regulatory pathway supported by a Regenerative Medicine Advanced Therapy Designation (RMAT).

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HOPE-3, a multi-center, double-blind, placebo-controlled study, includes 2 cohorts of non-ambulatory and ambulatory boys who are randomized to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during the first 12 months of the study. Cohort A, which included 58 individuals with DMD and impaired skeletal muscle function, is intended to support a biologics license application submission. Cohort B, which is currently enrolling, is expected to include 44 participants and is intended to support inclusion of the San Diego site following initial registration.

Investigators will use Performance of the Upper Limb (PUL) v2.0, a validated tool designed to assess high, mid, and distal function, as the primary outcome of the study. The trial will also incorporate other various secondary outcomes including cardiac function assessments.

Capricor announced positive data from its phase 2 HOPE-2 study (NCT03406780) in September 2021, with findings that showed that CAP-1002 met its primary end point on decline in mid-PUL version 1.2. In comparison with placebo, patients on active treatment showed a slowing of this outcome by 71% (P = .01). The trial also met additional end points, with significant differences seen on PUL v2.0 (P = .04) and cardiac end point of ejection fraction (P = .02) in comparison with placebo.2

More recently, in July 2023, the company announced positive data from the open-label extension (OLE) of HOPE-2 where patients showed continued improvement in left ventricular ejection fraction (LVEF) after 2 years of treatment with CAP-1002. In the OLE, patients received CAP-1002 at 150 million cells per infusion every 3 months over the course of 24 months. LVEF, measured using cardiac MRI, was improved in 6 of the 9 patients at the end of the HOPE-2 study. Over time, there was an increasing correlation between PUL v2.0 and ejection fraction results (r = 0.75; = .02). The therapy was well-tolerated with a safety profile that was consistent to previous observations.

1. 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 December 13, 2023.
2. Capricor Therapeutics announces positive final data from its phase 2 HOPE-2 trial in patients with Duchenne muscular dystrophy treated with CAP-1002. News release. Capricor Therapeutics. September 24, 2021. Accessed December 13, 2023.
3. 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 December 13, 2023.
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