Duchenne Muscular Dystrophy Cell Therapy CAP-1002 Demonstrates Improvements in LVEF

Capricor Therapeutics’ CAP-1002, an investigational allogeneic cardiosphere-derived cell therapy intended to treat Duchenne muscular dystrophy (DMD), has demonstrated improvements in left ventricular ejection fraction (LVEF) in new 24-month data from the HOPE-2 clinical trial (NCT03406780)’s open-label extension (OLE) study (HOPE-2-OLE; NCT04428476).¹

Among 9 patients who reached 24 months of follow-up in the OLE study, 6 patients showed improvement in LVEF as measured by cardiac magnetic resonance imaging in comparison to when they were assessed at the conclusion of HOPE-2. Capricor Therapeutics noted that this indicates preservation of cardiac function. In addition to the LVEF results, the company also reported that at 24 months of follow-up patients demonstrated statistically significant benefit (P = .021) on the Performance of the Upper Limb (PUL version 2.0) scale in comparison to the rate of decline seen in the placebo group in HOPE-2 at 1 year of follow-up. Furthermore, an increasing correlation between PUL version 2.0 and LVEF findings has been observed over time (24-month OLE results r = .75, P = .02). In terms of safety, CAP-1002 was reported to be well-tolerated and Capricor stated that the OLE study demonstrated a favorable safety profile.

“The results from this 2-year open label study are tremendously impactful for DMD patients showing cardiac and skeletal functional benefits, which underscores the potential long-term benefits of CAP-1002 treatment in DMD,” Linda Marbán, PhD, chief executive officer of Capricor Therapeutics, said in a statement.¹ “Importantly, the natural history of DMD cardiomyopathy suggests a steady decline in cardiac function as measured by ejection fraction, however, in HOPE-2-OLE, we observed improvements in heart function in 6 of 9 patients. Furthermore, as the HOPE-2-OLE data highlights the disease modifying potential of CAP-1002, we believe it is imperative to start treatment as early as possible to prevent the irreversible loss of muscle. Taken together with the favorable safety/tolerability profile, these data position CAP-1002 as a potential anchor therapy for DMD patients. We thank the patients, their families, caregivers, and the broader Duchenne community for continuing to work with us on this promising therapy.”

The PUL version 2.0 results were consistent with results previously reported in January 2023 for patients with 18 months of follow-up.² At that time, it also noted that patients who received CAP-1002 in HOPE-2-OLE, which recruited patients who had participated in HOPE-2, demonstrated attenuation of disease progression, regardless of whether they had been in the treatment group or the placebo group in HOPE-2. HOPE-2-OLE originally met its primary end point for PUL version 2.0 results at 1 year of follow-up (P = .02).¹ Notably, HOPE-2 included pediatric and young adult male patients with DMD who are not ambulatory. A phase 3 clinical trial evaluating CAP-1002, HOPE-3 (NCT05126758), is currently recruiting patients.

Capricor Therapeutics has a Type-B Clinical Meeting with the FDA planned for the third quarter of 2023.³ The company will use the meeting to discuss HOPE-3 and its plans for submitting a biologics license application (BLA) for CAP-1002. CAP-1002 has previously received regenerative medicine advanced therapy designation and orphan drug designation from the FDA.

“We are encouraged by the robust and consistent results observed to date and will continue to work closely with the US FDA to bring CAP-1002 to patients as quickly as possible,” Marbán added. “We plan to discuss these results as well as the key features of our ongoing phase 3 HOPE-3 trial and outline our proposed path towards submission of a potential BLA during our upcoming meeting with the FDA. In parallel, HOPE-3 continues to enroll patients and we remain on track to complete enrollment in the second half of 2023 and report the interim analysis in the fourth quarter of 2023.”

Substantial progress in the treatment landscape for DMD was recently made with the approval of Sarepta Therapeutics’ delandistrogene moxeparvovec (SRP-9001) on June 22, 2023.⁴ SRP-9001, which will be marketed under the name Elevidys, is indicated for ambulatory pediatric patients aged 4 through 5 years who have a confirmed mutation in the DMD gene, excepting those who have a deletion in exon 8 and/or exon 9. Other advanced therapeutics for muscular dystrophy indications have also made progress in their development pathways recently; last month, Benitec Biopharma received clearance from the FDA for its investigational new drug application for BB-301, an investigational adeno-associated virus vector-based silence and replace gene therapy intended to treat oculopharyngeal muscular dystrophy-related dysphagia.⁵

REFERENCES
1. Capricor Therapeutics announces positive 24-month results from ongoing HOPE-2 open label extension study of CAP-1002 in Duchenne muscular dystrophy. News release. Capricor Therapeutics. June 30, 2023. Accessed July 6, 2023. https://www.capricor.com/investors/news-events/press-releases/detail/255/capricor-therapeutics-announces-positive-24-month-results
2. Capricor Therapeutics announces positive 18-month results from ongoing HOPE-2 open label extension study of CAP-1002 in Duchenne muscular dystrophy patients. News release. Capricor Therapeutics. January 25, 2023. Accessed July 6, 2023. https://feeds.issuerdirect.com/news-release.html?newsid=7181150467767720
3. Capricor Therapeutics announces follow-up Type-B clinical meeting with the FDA for CAP-1002 for the treatment of Duchenne muscular dystrophy. News release. Capricor Therapeutics. June 7, 2023. Accessed July 6, 2023. https://www.capricor.com/investors/news-events/press-releases/detail/253/capricor-therapeutics-announces-follow-up-type-b-clinical
4. Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. June 22, 2023. Accessed July 6, 2023. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-approval-elevidys-first-gene?_ga=2.14016759.1120318671.1687966860-1064823149.1687449584
5. Benitec Biopharma receives FDA clearance of the IND for BB-301 for the treatment of oculopharyngeal muscular dystrophy. News release. Benitec Biopharma Inc. June 26, 2023. Accessed July 6, 2023. https://ir.benitec.com/news-events/press-releases/detail/102/benitec-biopharma-receives-fda-clearance-of-the-ind-for