FDA lifts hold on Rocket Danon disease trial

The U.S. FDA has lifted the clinical hold on Rocket Pharmaceuticals’ pivotal phase 2 trial of gene therapy, RP-A501, for the treatment of Danon disease.

Rocket had paused dosing in the trial at the request of the FDA back in May, 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.

Now, the FDA has confirmed that Rocket satisfactorily addressed issues outlined in the clinical hold. Rocket will collaborate with investigators to implement an immunomodulatory regimen more closely reflecting that administered in the phase 1 pediatric cohort. The FDA authorized the pivotal study to resume first 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. This adjusted dose aligns with the lower range of administered doses that were associated with efficacy across multiple biomarkers, echocardiographic and clinical endpoints in the phase 1 study.

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.