RP-A501 trial paused

Rocket Pharmaceuticals, Inc. announced an update related to RP A501, its investigational gene therapy for Danon disease. A patient participating in the Phase II pivotal trial of RP A501 experienced an unexpected Serious Adverse Event (SAE). The SAE involved clinical complications related to a capillary leak syndrome. Rocket is conducting a comprehensive root cause analysis and remains in active dialogue with the FDA and other key stakeholders, with the current focus being on the recent introduction of a novel immune suppression agent to the pre-treatment regimen that had been implemented to mitigate complement activation observed in some patients. This novel agent was specific to the AAV9-Danon program. Upon learning of the initial event, Rocket voluntarily paused further dosing in the study. On May 23, 2025, the FDA placed a clinical hold on the trial to allow for further evaluation. Rocket is deeply saddened to report that this patient has since passed away after an acute systemic infection.

Rocket is working with the FDA, the Independent Data Safety Monitoring Committee, clinical investigators, and scientific experts, and is committed to ensuring the safety of all study patients while resuming the trial as expeditiously as possible. While the clinical hold remains in place, the company is unable to provide guidance on the anticipated timing for completion of the Phase II trial.

“We are heartbroken by this loss and are fully committed to our mission to develop gene therapies that address the underlying cause of devastating diseases like Danon. We are immensely grateful for the patients and families who participate in this important research,” said Gaurav Shah, M.D., Chief Executive Officer of Rocket Pharmaceuticals.

RP-A501 Phase II Pivotal Trial Overview - The global, single-arm, multi-center Phase II pivotal trial evaluates the efficacy and safety of RP A501 in 12 patients with Danon disease, including a pediatric safety run-in (n=2), and a dose level of 6.7 x 1013 GC/kg. i) To support accelerated approval, the study assesses the efficacy of RP A501 as measured by the biomarker-based co-primary endpoint consisting of improvements in LAMP2 protein expression, and reductions in left ventricular mass. ii) Key secondary endpoint is change in troponin. Additional secondary endpoints include natriuretic peptides, Kansas City Cardiomyopathy Questionnaire, New York Heart Association class, event free survival to 24 months and treatment emergent safety events. These endpoints could support full approval with longer-term follow-up. iii) A global natural history study is running concurrently with the Phase II pivotal trial. iv) The pediatric run-in enrolled two patients in a sequential manner with a minimum three-month follow-up prior to subsequent enrollment. In addition, all patients enrolled in the trial are required to have a three-months observational pre-treatment run-in to enable an assessment of troponin (and other biomarker) trajectories to optimally assess this key secondary endpoint. Details about the Phase II study can be found at www.clinicaltrials.gov under NCT identifier NCT06092034.