FDA halts Rocket Pharma's RP-A501 trial for Danon disease

Rocket Pharmaceuticals, Inc., a fully integrated, late-stage biotechnology company advancing an integrated pipeline of genetic therapies for rare diseases, announced an update related to RP-A501, its investigational gene therapy for Danon disease.

A patient participating in the phase 2 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 US Food and Drug Administration (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 2 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.

Rocket extends our deepest sympathies to the patient’s family, caregivers, and the treating clinical team. Rocket also continues its longstanding collaboration with the Danon Foundation, whose commitment to research, advocacy, and patient support remains integral to advancing the field and improving outcomes for individuals affected by Danon disease.

Financial Position and Investment Outlook

As of March 31, 2025, Rocket had cash, cash equivalents, and investments of $318.2 million. The company is prioritizing investment in its AAV platform while assessing ways to optimize value for the rest of the pipeline.

This will translate into a reduction in overall cash spend. Rocket now expects its existing resources will be sufficient to fund operations into 2027, excluding any potential proceeds from the sale of Priority Review Vouchers that could follow the approval of therapies from the haematology portfolio.

Phase 2 Pivotal Trial Design and Endpoints

The global, single-arm, multi-center Phase 2 pivotal trial evaluates the efficacy and safety of RP-A501 in 12 patients with Danon disease, including a paediatric safety run-in (n=2), and a dose level of 6.7 x 10¹³ GC/kg.

Primary and Secondary Endpoints

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.

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.

A global natural history study is running concurrently with the Phase 2 pivotal trial. The paediatric 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.

About RP-A501

RP-A501 is Rocket’s investigational gene therapy product for the treatment of Danon disease and the first gene therapy for a cardiovascular condition to demonstrate safety and efficacy in clinical studies. Danon disease is 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 harbouring mutations in the endogenous LAMP2 gene, has the potential to fully restore cardiac function at its root. RP-A501 represents a single dose treatment and is administered as an intravenous infusion.

In preclinical and clinical studies, AAV9.LAMP2B has been shown to target cardiac cells (cardiomyocytes) and deliver the functional LAMP2B gene to heart tissue, which ultimately leads to improved cardiac structure and function in patients.

Regulatory Designations and Approvals

In 2023, the US Food and Drug Administration granted regenerative medicine advanced therapy designation, and the European Medical Agency granted PRIority MEdicines (PRIME) eligibility to RP-A501.

About Danon Disease

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.

This results in accumulation of autophagosomes and glycogen, particularly in cardiac muscle and other tissues, which ultimately leads to heart failure, and for male patients, frequent death during adolescence or early adulthood. It is estimated to have a prevalence of 15,000 to 30,000 patients in the US and Europe.

The only available treatment option for Danon disease is cardiac transplantation, which is associated with substantial complications and is not considered curative, representing the high unmet medical need for patients with Danon disease.

In 2023, Rocket secured an ICD-10 code from the Centers for Medicare and Medicaid Services (CMS) to document patients with LAMP2 deficiency in Danon disease.

About Rocket Pharmaceuticals

Rocket Pharmaceuticals, Inc. is a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare disorders.

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