Biotechnology company Rocket Pharmaceuticals Inc (NASDAQ: RCKT) announced on Wednesday that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on its pivotal Phase 2 trial of RP-A501 for Danon disease, less than three months after the hold was issued. The FDA confirmed Rocket satisfactorily addressed the prior concerns and authorised the trial to resume with a recalibrated dose of 3.8 x 10¹³ GC/kg in three sequential patients, with a minimum four-week interval between treatments.

RP-A501 is an investigational gene therapy designed to restore or stabilize cardiac function in Danon disease patients by delivering a functional LAMP2B transgene via a recombinant AAV9 vector. The therapy has previously demonstrated safety and efficacy in Phase 1 studies, targeting cardiac cells to improve structure and function. RP-A501 holds FDA RMAT, Fast Track, Rare Pediatric and Orphan Drug designations in the US, along with ATMP and PRIME designations in the EU.

The Phase 2 pivotal trial is a global, single-arm, multi-centre study of 12 patients assessing efficacy and safety. Co-primary endpoints include improvements in LAMP2 protein expression and reductions in left ventricular mass, while secondary endpoints track troponin, natriuretic peptides, functional status, event-free survival to 24 months, and treatment-emergent safety events. A three-month pre-treatment observation period is required to establish baseline biomarker trajectories.

Danon disease is a rare X-linked lysosomal-associated disorder primarily affecting the heart, skeletal muscle, and brain, leading to heart failure and early mortality in male patients. Cardiac transplantation remains the only treatment option, highlighting the high unmet medical need. Rocket's ongoing pipeline also includes AAV-based programs for PKP2-associated arrhythmogenic cardiomyopathy and BAG3-associated dilated cardiomyopathy, as well as lentiviral-based therapies for rare hematology disorders including LAD-I, Fanconi anemia and pyruvate kinase deficiency.