Rocket touts positive safety data in modified Danon disease trial

Rocket Pharmaceuticals announced a positive clinical safety update regarding the initial three patients treated under the modified protocol for its global, pivotal phase 2 trial of its gene therapy, RP-A501, in Danon disease.

Rocket had paused dosing in the trial at the request of the FDA in May 2025, after a patient experienced clinical complications related to a capillary leak syndrome. The patient then passed away after an acute systemic infection. Rocket conducted a comprehensive root cause analysis, with the focus on the introduction of a novel immune suppression agent to the pre-treatment regimen that had been implemented to mitigate complement activation observed in some patients.

The FDA authorized the pivotal study to resume in August 2025 with a recalibrated dose of 3.8 x 10¹³ GC/kg of RP-A501 in three patients, treated sequentially with a minimum four-week interval between each treatment. The adjusted dose aligned with the lower range of administered doses that were associated with efficacy across multiple biomarkers, echocardiographic and clinical endpoints in the phase 1 study.

Rocket says no thrombotic microangiopathy, capillary leak syndrome, or other significant safety concerns have been observed in the three patients. The phase 2 trial was designed as a 12-patient, single-arm study. Rocket is working with the FDA to align on the path to dosing additional patients and completing the trial and expects to provide a regulatory update in the second half of 2026.

RP-A501 is a single dose treatment administered as an intravenous infusion for the treatment of Danon disease, a rare, serious cardiac and skeletal myopathy caused by mutations in the LAMP2 gene. RP-A501 consists of a recombinant adeno-associated serotype 9 (AAV9) capsid containing a full-length, wild-type version of the human LAMP2B transgene (AAV9.LAMP2B) which, when inserted into heart cells harboring mutations in the endogenous LAMP2 gene, has the potential to fully restore cardiac function at its root.