FDA Places Rocket Pharmaceuticals’ RP-A501 Danon Disease Clinical Trial on Hold

CRANBURY, N.J.–(BUSINESS WIRE)–May 27, 2025  Rocket Pharmaceuticals, Inc. (Nasdaq: TSHA) today confirmed the death of a patient in its pivotal Phase II trial for AAV9-based gene therapy RP-A501 for Danon disease. The U.S. FDA has placed the study on clinical hold following this tragic event.

The patient experienced a serious adverse event (SAE) involving capillary leak syndrome (CLS) after receiving RP-A501 in early May. Rocket’s CEO, Gaurav Shah, MD, extended condolences, emphasizing a full investigation into the circumstances. Further dosing in the trial has been voluntarily paused.

Rocket’s investigation is primarily focused on a novel immune suppression agent recently added to the pre-treatment regimen for its AAV9-Danon program to mitigate complement activation. The company is evaluating if this agent influenced immune responses unexpectedly, causing CLS. A second patient also showed early CLS signs after receiving this modified regimen, supporting this hypothesis. While the AAV9 vector cannot be fully excluded, the focus remains on the C3 inhibitor.

RP-A501 is a single-dose AAV9-based gene therapy (AAV9.LAMP2B) designed to restore cardiac function in Danon disease. It holds RMAT and PRIME designations. The clinical hold has led to stock volatility and analyst downgrades.

Rocket will prioritize spending on its AAV platform and manage cash into 2027. The Phase II trial aims to assess RP-A501’s efficacy and safety in 12 male Danon disease patients (≥8 years), using LAMP2 protein expression and left ventricular mass as co-primary endpoints.

Danon disease is a rare, X-linked disorder caused by LAMP-2 gene mutations, leading to heart failure. There’s an urgent need for effective AAV gene therapies like RP-A501.