Rocket Pharmaceuticals has reported a positive clinical safety update from the initial 3 patients treated under a modified protocol for its pivotal phase 2 trial of RP-A501 in Danon disease, with no thrombotic microangiopathy (TMA), capillary leak syndrome, or other significant safety concerns observed to date.1
"These encouraging early safety observations from the initial three patients treated with RP-A501 reinforce our strong confidence in the program that was built on transformative results from the phase 1 trial which reflect the potential of gene therapy to address genetic cardiomyopathies," said Gaurav Shah, MD, chief executive officer of Rocket Pharmaceuticals, in a company press release.1
Key facts
- Drug: RP-A501, AAV9 gene therapy (LAMP2B transgene)
- Indication: Danon disease
- Status: Positive safety update, initial 3 patients dosed
- Trial: Modified pivotal phase 2, 12-patient, single-arm
- Safety: No TMA or capillary leak syndrome observed
- Next steps: FDA regulatory pathway update expected 2H 2026
What did the modified protocol involve?
The 3 patients received RP-A501 at a recalibrated dose of 3.8 x 1013 GC/kg, together with a refined immunomodulatory regimen comprising rituximab, sirolimus, and corticosteroids. Treatment proceeded sequentially, with a minimum of 4 weeks between infusions. The pivotal phase 2 trial is designed as a 12-patient, single-arm study.1
"The recalibrated phase 2 dose was selected with the expectation that it will deliver potency consistent with the dose at which RP-A501 demonstrated meaningful efficacy in patients in phase 1," said Syed Rizvi, MD, chief medical officer, Rocket Pharmaceuticals, in the release.1 "This recalibration accounts for the higher proportion of full capsids in the current drug product in the setting of Danon disease and was developed in consultation with leading experts and the FDA."1
What comes next for the trial?
Rocket is actively engaging with FDA to align on a path to dosing additional patients and completing the pivotal phase 2 trial under the modified protocol, with a regulatory pathway update expected in the second half of 2026. The company also said it remains on track to provide a comprehensive Danon disease program update in the second half of 2026.1