Rare Daily Staff

The U.S. Food and Drug Administration lifted the hold on Rocket Pharmaceuticals’ phase 1 clinical trial of RP-A501 for the treatment of Danon disease after the company modified the trial protocol, guidelines, and other supporting documents.

Rocket’s Danon disease program was placed on clinical hold by the FDA in May of 2021 to modify the study protocol and other supporting documents with revised guidelines for patient selection and safety management. No new drug-related safety events were observed in the low-dose or higher-dose young adult cohorts as part of the clinical hold or during the hold.

The company said it has initiated steps to resume the program as soon as possible and expects to commence dosing in the low-dose pediatric patient cohort in the third quarter.

Danon disease is a rare X-linked inherited disorder caused by mutations in the gene encoding lysosome-associated membrane protein 2 (LAMP-2), an important mediator of autophagy, a process of cellular waste removal. This results in accumulation of autophagosomes and glycogen, particularly in cardiac muscle and other tissues, which ultimately leads to heart failure, and for many male patients, death during adolescence or early adulthood. It is estimated to have a prevalence of 15,000 to 30,000 patients in the United States and the European Union. The only available treatment option for Danon disease is cardiac transplantation, which is associated with substantial complications and is not considered curative. There are no specific therapies available for the treatment of Danon disease.

RP-A501 is an investigational gene therapy product being developed for Danon disease and the first potential gene therapy for monogenic heart failure. It consists of a recombinant adeno-associated serotype 9 capsid containing a functional version of the human LAMP2B transgene. RP-A501 is currently being evaluated in an ongoing phase 1 clinical trial, in which the company observed preliminary activity data of RP-A501 as well as a favorable tolerability profile.

The non-randomized, open-label phase 1 trial is designed to enroll both pediatric and young adult male patients to assess the safety and tolerability of a single intravenous infusion of RP-A501. Additional outcome measures include cardiomyocyte and skeletal muscle transduction by gene expression, histologic correction via endomyocardial biopsy and clinical stabilization via cardiac imaging and functional cardiopulmonary testing.

“We are moving as quickly as possible to resume dosing and commence treatment this quarter,” said Gaurav Shah, CEO of Rocket Pharma. “Additionally, given the activity observed among young adults in our low-dose cohort, in agreement with the FDA, we are now proceeding with the pediatric cohort. This is another important step forward as we believe the pediatric Danon population has the potential to realize the maximum benefit from our Danon disease gene therapy program.”

Photo: Gaurav Shah, CEO of Rocket Pharma

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