The company stated that based on the meeting, the trial’s primary end points will remain the same.
Capricor Therapeutics has received feedback from the FDA in a Type-B meeting on the design of its HOPE-3 clinical trial (NCT05126758) evaluating CAP-1002, an investigational allogeneic cardiosphere-derived cell therapy intended to treat Duchenne muscular dystrophy (DMD), thus helping to establish a roadmap to a biologics license application (BLA) for the product.1
Capricor emphasized that the meeting helped to align the company with the FDA on important aspects of the trial, which is expected to enroll approximately 6 more patients beyond its current set of 52 participants by the end of the year, for a total final enrollment of approximately 58 patients. The company stated that based on the meeting, the trial’s primary end points will remain the same. According to the clinicaltrials.gov page for HOPE-3, the study’s primary end point is the mean change from baseline in the full Performance of the Upper Limb (PUL version 2.0), measured at 12 months posttreatment. Capricor also noted that it anticipates reporting topline results from the trial in the final quarter of 2024 and submission of a BLA in 2025. The results supporting the BLA will be based off cell therapy product produced at the company’s Los Angeles manufacturing facility, however HOPE-3 will also include a cohort that will be treated with product produced at a separate facility in San Diego. The Type B meeting also involved discussion of potential alternative paths to approval; Capricor stated that it anticipates further discussion of these plans after HOPE-3 reaches full enrollment.
"We are pleased to have reached an important regulatory milestone that further defines the path towards registration of CAP-1002 for DMD and brings us potentially 1 step closer to addressing the great unmet medical need for these patients,” Linda Marbán, PhD, the chief executive officer of Capricor, said in a statement.1 “During recent meetings with the FDA, we aligned on key features of HOPE-3, which as currently designed, and if successful, is expected to provide sufficient evidence of effectiveness to support our BLA submission and significantly expedites our path towards potential approval of CAP-1002. In addition, although product from our San Diego site would not be required to support registration of CAP-1002, we do plan to enroll a separate cohort with product manufactured from our San Diego site, with a view toward meeting potential increased commercial demand following initial registration.”
A few months ago, in July, Capricor reported positive 24-month data from a separate evaluation of CAP-1002: the HOPE-2 clinical trial (NCT03406780)’s open-label extension (OLE) study (HOPE-2-OLE; NCT04428476).2 Among 9 patients who reached 24 months of follow-up in the OLE study, 6 patients showed improvement in left ventricular ejection fraction (LVEF) as measured by cardiac magnetic resonance imaging in comparison to when they were assessed at the conclusion of HOPE-2. 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 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.
“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,” Marbán said in a statement at the time.2 “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.”
Although a gene therapy for DMD, Sarepta Therapeutics’ delandistrogene moxeparvovec (Elevidys), was already approved earlier this year using microdystrophin as a surrogate end point, regulators have struggled to come to a consensus on the validity of this measure for clinical benefit in pivotal clinical trials in the accelerated approval pathway.3,4 As such, companies are continuing to evaluate other advanced therapeutic approaches, such as cell therapy, to treating the disorder. In June, CGTLive™ covered some of these investigational alternatives, including CAP-1002 and ENCell’s EN001, an allogeneic umbilical cord-derived mesenchymal stem cell product that has been evaluated in a phase 1 clinical trial (NCT05338099).