NEW YORK – Rocket Pharmaceuticals said Tuesday that it has finished enrolling patients into a pivotal Phase II trial of its gene therapy RP-A501 for Danon disease.
Danon disease is a rare X-linked disorder caused by mutations in the LAMP2 gene, which encodes the lysosome-associated membrane protein 2 that is important for autophagy. These mutations lead to the accumulation of autophagosomes and glycogen, including in cardiac muscle, which then contributes to heart failure and often death in adolescence or early adulthood. Current treatment for Danon disease is heart transplantation, but it is not curative.
The company has enrolled 12 male patients in the US and European Union into its single-arm multicenter Phase II pivotal trial of RP-A501, an adeno-associated viral vector-based gene therapy that aims to treat Danon disease by inserting a LAMP2B transgene into cardiac cells to restore function.
Following a two-patient safety run-in, the trial is evaluating the safety and efficacy of the treatment. Efficacy will be determined by assessing changes in LAMP2 protein expression and reduction in left ventricular mass, endpoints the company said would support its application for accelerated approval.
Rocket previously said it discussed the Phase II trial design with the US Food and Drug Administration and would seek accelerated approval for RP-A501. The company said it will pursue regulatory filings simultaneously in the US and outside the US.
Investigators will also assess as secondary endpoints changes in troponin levels as well as natriuretic peptides levels and event-free survival. At the same time as the Phase II study, investigators will also run a global natural history study to collect prospective longitudinal and retrospective clinical data on patients with Danon disease.
Cranbury, New Jersey-based Rocket is further enrolling patients into a Phase I dose-escalation trial of another gene therapy, RP-A601, for plakophilin-2 related arrhythmogenic cardiomyopathy.