Rocket Pharmaceuticals Updates Phase 2 RP-A501 Trial for Danon Disease

CRANBURY, N.J. — On May 27, 2025, Rocket Pharmaceuticals, Inc., a late-stage biotechnology company listed on NASDAQ under the symbol RCKT, shared an update regarding its gene therapy candidate, RP-A501, for Danon disease. A significant development has occurred in the Phase 2 pivotal trial of RP-A501, where a participating patient experienced a Serious Adverse Event (SAE) leading to severe complications. These complications were related to capillary leak syndrome, a condition that emerged following the introduction of a new immune suppression agent in the study's pre-treatment regimen. This agent was designed to address complement activation in the AAV9-Danon program.

Upon encountering this adverse event, Rocket Pharmaceuticals promptly decided to halt further dosing in the study. Subsequently, on May 23, 2025, the U.S. Food and Drug Administration (FDA) imposed a clinical hold on the trial to allow for a thorough investigation. Tragically, the patient involved succumbed to an acute systemic infection. Rocket Pharmaceuticals is actively collaborating with the FDA, an Independent Data Safety Monitoring Committee, clinical investigators, and scientific experts to ensure the safety of all participants while striving to resume the trial expeditiously. At present, there is no clear timeline for the trial's completion due to the ongoing clinical hold.

Dr. Gaurav Shah, CEO of Rocket Pharmaceuticals, expressed deep sorrow over the patient's passing and reaffirmed the company's commitment to developing gene therapies for severe diseases like Danon. He acknowledged the crucial role played by patients and families in advancing research. The company extended condolences to the patient's family, caregivers, and healthcare team. Rocket Pharmaceuticals also continues to work closely with the Danon Foundation, emphasizing research and patient advocacy to enhance outcomes for those affected by Danon disease.

Financially, Rocket Pharmaceuticals reported having $318.2 million in cash, cash equivalents, and investments as of March 31, 2025. The company intends to focus its investments on the AAV platform and explore avenues to maximize the value of its pipeline. This strategy aims to reduce overall cash expenditures, allowing its current resources to sustain operations into 2027, not accounting for possible revenue from Priority Review Vouchers following approval of therapies from its hematology portfolio.

The company will hold a conference call on May 27, 2025, at 8:30 a.m. ET to discuss these developments. Further information for joining the call is available on the Rocket Pharmaceuticals website.

The Phase 2 pivotal trial of RP-A501 is a global, single-arm study involving multiple centers. It aims to evaluate the safety and efficacy of RP-A501 in 12 patients diagnosed with Danon disease. The trial includes a pediatric safety run-in and assesses the treatment's effectiveness using a biomarker-based co-primary endpoint focused on improvements in LAMP2 protein expression and reductions in left ventricular mass. Secondary endpoints examine changes in troponin levels, natriuretic peptides, and other cardiac health indicators. A parallel global natural history study is also being conducted to support this trial.

RP-A501 is a pioneering gene therapy for Danon disease and is recognized for its potential to restore cardiac function in patients with LAMP2 gene mutations. The therapy uses an adeno-associated virus serotype 9 to deliver the LAMP2B gene directly to heart cells, which has shown promise in improving heart structure and function in both preclinical and clinical settings. In 2023, RP-A501 received regenerative medicine advanced therapy designation from the FDA and PRIME eligibility from the European Medical Agency.

Danon disease, a rare inherited disorder linked to mutations in the LAMP2 gene, leads to the accumulation of autophagosomes and glycogen in cardiac muscles, resulting in heart failure. The disorder is particularly severe in male patients, often leading to early mortality. As of now, heart transplantation is the sole treatment option, emphasizing the urgent need for novel therapies like RP-A501.