Rocket Pharmaceuticals (NASDAQ: RCKT) has announced the completion of enrollment in its global Phase 2 pivotal clinical trial evaluating RP-A501, a gene therapy for the treatment of male patients with Danon disease. The trial, which enrolled 12 patients, is designed to assess the efficacy and safety of RP-A501 in addressing this rare and life-threatening condition.
The Phase 2 trial (NCT06092034) is a single-arm, multi-center study that includes a pediatric safety run-in with two patients, followed by enrollment of the remaining ten patients across sites in the United States and the European Union. All patients receive a dose of 6.7 x 10^13 GC/kg of RP-A501, administered as an intravenous infusion.
Barry H. Greenberg, MD, FHFSA, Director of the Advanced Heart Failure Treatment Program at UC San Diego Health, noted, "We are moving closer to the goal of having a treatment for patients with Danon disease. The rapid recruitment of the Phase 2 trial signifies the positive views of the study clinicians regarding this investigational therapy."
Trial Design and Endpoints
The study's co-primary endpoints are 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 (NYHA) class, event-free survival up to 24 months, and treatment-emergent safety events. These secondary endpoints are designed to support full approval with longer-term follow-up.
A global natural history study is being conducted concurrently with the Phase 2 trial to provide comparative data. All patients enrolled in the trial undergo a three-month observational pre-treatment run-in to assess troponin and other biomarker trajectories, optimizing the assessment of key secondary endpoints.
About RP-A501
RP-A501 is an investigational gene therapy designed to address the underlying genetic cause of Danon disease, which is caused by mutations in the LAMP2 gene. The therapy consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a full-length, wild-type version of the human LAMP2B transgene (AAV9.LAMP2B). When delivered to heart cells, RP-A501 aims to restore cardiac function by providing a functional copy of the LAMP2 gene.
The FDA has granted RP-A501 regenerative medicine advanced therapy designation, and the European Medical Agency has granted PRIority MEdicines (PRIME) eligibility.
Danon Disease: An Unmet Need
Danon disease is a rare X-linked inherited disorder caused by mutations in the LAMP2 gene, leading to the accumulation of autophagosomes and glycogen, particularly in cardiac muscle. This accumulation results in heart failure and, frequently, death during adolescence or early adulthood for male patients. The estimated prevalence of Danon disease is 15,000 to 30,000 patients in the U.S. and Europe.
Currently, the only available treatment option for Danon disease is cardiac transplantation, which is associated with significant complications and is not considered curative. This highlights the high unmet medical need for effective therapies for Danon disease.
