Rocket Pharmaceuticals Completes Enrollment in Phase 2 Trial of RP-A501 for Danon Disease

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a biotechnology company specializing in genetic therapies for rare disorders, has announced the completion of patient enrollment in its global Phase 2 clinical trial for the treatment of Danon disease using RP-A501. This pivotal clinical trial aims to address the high unmet medical need for effective treatments for male patients suffering from this rare genetic condition.

The Phase 2 trial, which is evaluating the safety and efficacy of RP-A501, enrolled 12 patients in total, including an initial two-patient safety run-in. Following the successful safety run-in and the activation of global trial sites, the remaining 10 patients were enrolled across both the United States and the European Union within a span of three months. The company plans to seek regulatory approvals concurrently in the U.S. and internationally, reflecting the global prevalence of Danon disease.

Barry H. Greenberg, MD, FHFSA, Director of the Advanced Heart Failure Treatment Program at UC San Diego Health, emphasized the significance of this development for the Danon patient community. He noted the eagerness among patients and clinicians for this innovative one-time treatment, designed to improve cardiac abnormalities and preserve normal cardiac function by delivering functional LAMP2B genes to the heart tissue.

RP-A501's pivotal Phase 2 trial is structured as a global, single-arm, multi-center study focused on 12 patients with Danon disease. The trial includes a pediatric safety run-in and evaluates a dose level of 6.7 x 10^13 GC/kg. The study's primary endpoints are based on biomarkers, specifically improvements in LAMP2 protein expression and reductions in left ventricular mass. Secondary endpoints include changes in troponin levels, natriuretic peptides, Kansas City Cardiomyopathy Questionnaire scores, New York Heart Association class, event-free survival up to 24 months, and treatment emergent safety events. These endpoints may support full approval with extended follow-up.

Additionally, a global natural history study is being conducted concurrently with the Phase 2 trial. This study involves a three-month observational pre-treatment run-in for all enrolled patients, aiming to optimally assess key secondary endpoints such as troponin trajectories.

RP-A501, Rocket's investigational gene therapy product for Danon disease, is the first gene therapy to demonstrate safety and efficacy in clinical studies for a cardiovascular condition. Danon disease, caused by mutations in the LAMP2 gene, leads to the accumulation of autophagosomes and glycogen in cardiac muscle and other tissues, eventually resulting in heart failure. The disease predominantly affects male patients, who often face early mortality in adolescence or early adulthood. With an estimated prevalence of 15,000 to 30,000 patients in the U.S. and Europe, the only current treatment option is cardiac transplantation, which carries significant risks and is not curative.

RP-A501 consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a full-length, wild-type version of the human LAMP2B transgene. When introduced into heart cells with LAMP2 gene mutations, this therapy has the potential to restore cardiac function. Administered as a single intravenous infusion, RP-A501 has shown promising results in preclinical and clinical studies, targeting cardiac cells and improving cardiac structure and function.

In 2023, RP-A501 received regenerative medicine advanced therapy designation from the U.S. Food and Drug Administration and PRIority MEdicines (PRIME) eligibility from the European Medical Agency. Rocket Pharmaceuticals also secured an ICD-10 code from the Centers for Medicare and Medicaid Services to document patients with LAMP2 deficiency in Danon disease.

Rocket Pharmaceuticals is dedicated to advancing genetic therapies for complex and rare disorders. Their pipeline includes programs for Fanconi Anemia, Leukocyte Adhesion Deficiency-I, Pyruvate Kinase Deficiency, and cardiovascular conditions like Danon disease. Through innovative gene therapy approaches, Rocket aims to offer transformative treatments that improve and extend the lives of individuals with these challenging conditions.