Capricor Announces Partnership for DMD Therapy CAP-1002 Ahead of Phase 3 Study

Linda Marbán, PhD

Capricor Therapeutics, a biotechnology company developing the investigational treatment CAP-1002 for patients with Duchenne muscular dystrophy (DMD), announced ahead of the initiation of its upcoming phase 3 HOPE-3 study (NCT05126758) that it has entered into a partnership with Nippon Shinyaku Co (NS Pharma), for the exclusive commercialization and distribution of the therapy in the United States.¹

Linda Marbán, PhD, chief executive office, Capricor, said in a statement that the partnership “aligns us with a larger, seasoned pharmaceutical company experienced in rare disease with specific expertise in DMD,” citing NS Pharma’s 2020 approval and launch of vitolarsen (Viltepso) for patients with DMD amenable to exon 53 skipping—at the time, only the second FDA-approved therapy for this specific DMD gene mutation that affects 8% to 10% of patients.²

“Our initial planned indication is for late-stage DMD patients with more advanced disease. Presently, this comprises approximately half of all DMD patients. Indication expansion to younger boys is something we hope to look at in the future as well as potential synergies with other developing therapies including gene therapy and oligonucleotides” Marbán added.

Under the terms of the agreement with NS Pharma, Capricor is responsible for conducting HOPE-3 and manufacturing CAP-1002, while NS Pharma will be responsible for the distribution of CAP-1002 in the United States. Capricor will sell commercial product to Nippon Shinyaku and will receive a meaningful, double-digit share of product revenue and additional development and sales-based milestone payments, including an upfront payment of $30 million.¹

READ MORE: Positive Phase 3 Topline Results Announced for Zilucoplan in Generalized Myasthenia Gravis

HOPE-3 will be a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of CAP-1002 in study participants with DMD, a population that will include both nonambulatory and ambulatory boys and young men who meet eligibility criteria. The estimated 68 participants will be randomly assigned to receive either CAP-1002 at a dose of 150 million cardiosphere-derived cells (CDCs) or placebo, every 3 months for a total of 4 doses, over a 12-month period. The primary end point will be the mean change in full upper limb function at month 12, as measured by Performance of Upper Limb 2.0 (PUL v1.2) scores. The secondary outcome measure will be cardiac muscle function and structure, as measured by change from baseline in ejection fraction. The study is expected to complete in late June 2024.

In late 2021, positive data from the phase 2 HOPE-2 study (NCT03406780) of the cardiac-derived cell therapy were announced, with CAP-1002 meeting its primary end point of decline on Mid-level Performance of Upper Limb 1.2 (PUL v1.2). The decline for those treated with CAP-1002 slowed by 71% (P = .01) compared with placebo. HOPE-2 also met additional end points, with significant differences seen on the Full PUL v2.0 (P = .04) and Cardiac Endpoint of Ejection Fraction (P = .002) compared with placebo.³

HOPE-2 enrolled 20 participants (12 placebo and 8 treated) with DMD across 9 sites in the US. These participants were on a stable regimen of steroids and around 80% were non-ambulant, with other demographic and baseline characteristics similar between the 2 groups. Participants were treated via intravenous delivery with either 150 million cells of CAP-1002 or placebo every 3 months, for a total of 4 doses over 1 year. Those data were presented at the World Muscle Society Virtual Congress, September 20-24.³

“This groundbreaking study is extremely exciting as we saw statistically significant changes of CAP-1002 in both skeletal and cardiac function. For these older boys who have limited therapeutic options, these data support the belief that CAP-1002 may become an important therapeutic option and possibly slow the progression of DMD,” HOPE-2 principal investigator Craig McDonald, MD, professor and chair, Department of Physical Medicine and Rehabilitation, UC Davis, said in a statement in September 2021.³

CAP-1002 is an allogeneic off-the-shelf cell therapy, and its immunomodulatory properties, as well as its ability to regenerate skeletal and cardiac muscle cells, have previously been demonstrated in preclinical studies. It was previously granted orphan drug designation by the FDA in 2015, and is also supported by regenerative medicine advanced therapy and orphan drug designations.^1,4

REFERENCES
1. Capricor Therapeutics and Nippon Shinyaku Enter Partnership for Exclusive Commercialization and Distribution of CAP-1002 for the Treatment of Duchenne Muscular Dystrophy in the US. News release. Capricor. January 25, 2022. Accessed February 4, 2022. https://www.irdirect.net/prviewer/release_only/id/5008537
2. FDA approves targeted treatment for rare Duchenne muscular dystrophy mutation. News release. FDA. August 12, 2020. Accessed February 4, 2022. https://www.prnewswire.com/news-releases/fda-approves-targeted-treatment-for-rare-duchenne-muscular-dystrophy-mutation-301111213.html
3. 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 February 4, 2022. https://www.globenewswire.com/news-release/2021/09/24/2302866/0/en/Capricor-Therapeutics-Announces-Positive-Final-Data-From-its-Phase-2-HOPE-2-Trial-in-Patients-with-Duchenne-Muscular-Dystrophy-Treated-with-CAP-1002.html
4. Capricor granted FDA orphan drug designation for allogenic cardiosphere-derived cells for the treatment of Duchenne muscular dystrophy. News release. Capricor Therapeutics. April 22, 2015. Accessed February 4, 2022. http://www.irdirect.net/pr/release/id/1253025