Rocket Pharmaceuticals says three patients have been safely dosed with its one‑time Danon gene therapy, RP‑A501, in a relaunched Phase II trial (NCT06092034) after a protocol revision prompted by a previous patient fatality. The patients received a recalibrated dose plus rituximab, sirolimus and corticosteroids, and no capillary leak syndrome, vascular injury or other serious adverse events have been reported to date. Company leaders say they are working with the FDA to enrol more patients and aim to complete the pivotal trial promptly, with an update expected in H2 2026.
Rocket Flags Safety for Danon Gene Therapy After Phase II Protocol Revision — No SAEs in First Three Patients
Three patients have safely received Rocket's gene therapy for Danon disease thus far following a protocol amendment. Credit: Corona Borealis Studio / Shutterstock.com.
Rocket Pharmaceuticals reports that three patients have been safely treated with its one‑time gene therapy for Danon disease, RP‑A501, in a Phase II trial after a protocol amendment prompted by a prior patient fatality.
The US Food and Drug Administration (FDA) approved a relaunch of the single‑arm pivotal study (NCT06092034) under an updated protocol in August 2025. Following that clearance, Rocket dosed three patients with a recalibrated RP‑A501 dose administered alongside an immunosuppressive regimen of rituximab, sirolimus and corticosteroids.
Why the Trial Was Paused
The study had been paused after a patient fatality linked to capillary leak syndrome. That event occurred after Rocket added a complement C3 inhibitor to the regimen without informing investors, triggering regulatory scrutiny and the subsequent protocol revision.
Early Safety Signals After Protocol Change
Since implementing the amended protocol, Rocket says none of the treated patients have experienced capillary leak syndrome, vascular injury or any other serious adverse events (SAEs) following RP‑A501 dosing. Citing these early safety signals, CEO Gaurav Shah said the company is in discussions with the FDA about how to treat additional patients and complete the pivotal trial 'as promptly as possible.'
Syed Rizvi, Chief Medical Officer: 'We selected the recalibrated Phase II dose with the expectation that it will deliver potency consistent with the dose at which RP‑A501 demonstrated meaningful efficacy in Phase I. This recalibration accounts for a higher proportion of full capsids in the current drug product and was developed in consultation with leading experts and the FDA to optimise the benefit‑risk profile.'
What RP‑A501 Aims To Do
RP‑A501 is designed as a 'one‑and‑done' viral gene therapy to deliver a functional copy of the LAMP2B gene to cardiac cells. Rocket's hypothesis is that restoring LAMP2B function will reinstate cellular waste recycling and potentially stabilise or improve cardiac function in patients with Danon disease.
Regulatory Path And Next Steps
If Phase II data support efficacy and safety, Rocket could use this pivotal study as the basis for a regulatory filing for RP‑A501 in Danon disease. The programme would expand Rocket's pipeline following the approval of Kresladi (marnetegragene autotemcel) for severe leukocyte adhesion deficiency (LAD). Rocket expects to provide an update on the Danon programme in the second half of 2026.
Originally published by Clinical Trials Arena, a GlobalData brand.
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