Rocket Pharma’s AAV Gene Therapy Shows Promise in Inherited Heart Disease

CRANBURY, N.J.–(BUSINESS WIRE)–May 15, 2025   Rocket Pharmaceuticals presented encouraging early Phase 1 data for its AAVrh74-based gene therapy, RP-A601, at the ASGCT conference. This AAV therapy targets plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM), a serious inherited heart condition. The AAV vector is designed to deliver the necessary genetic material to address the underlying cause of the disease.

The initial data from three patients treated with a single dose of the AAV gene therapy (8.0E13 GC/kg) demonstrated a well-tolerated safety profile over a follow-up period of up to 12 months. No dose-limiting toxicities related directly to the AAV administration were observed, and most treatment-emergent adverse events were mild to moderate. One severe adverse event, believed to be related to the immunosuppression regimen required with AAV gene therapy, resolved within two months. All patients experienced temporary elevations in liver enzymes, a known potential side effect of AAV-based gene therapies.

Importantly, the preliminary data also indicated potential efficacy of the AAV treatment. The therapy showed improvements in arrhythmia burden and a normalization of myocardial structure in the treated patients. Notably, two of the three patients improved from NYHA class II heart failure (slight limitation of activity) to NYHA class I (no clinical signs of heart failure) at 12 and six months, respectively, following the AAV gene transfer. Right ventricular systolic function remained stable across all patients. Cardiac biopsies confirmed an increase in PKP2 protein expression, the deficient protein in PKP2-ACM, demonstrating successful transduction by the AAV vector.

Rocket CEO Dr. Gaurav Shah hailed the data as “highly encouraging,” suggesting potential clinical benefit alongside a favorable safety profile for their AAV approach. William Blair analysts echoed this enthusiasm, stating the early data sets “a new bar for PKP2-ACM in terms of efficacy” and validates the safety and efficiency of the chosen dose of the AAV vector. They also suggested this data could support discussions for an accelerated approval pathway for this novel AAV-delivered therapy.

While acknowledging the encouraging safety data of the AAV treatment in this small cohort, the analysts noted that RP-A601 utilizes the same AAV vector serotype as Sarepta’s Elevidys, which was recently linked to a patient death in Duchenne muscular dystrophy. Consequently, they recommended a cautious approach to immunosuppression often required in AAV gene therapy to manage immune responses to the viral vector. Rocket has decided against further dose escalation of the AAV therapy due to the observed activity at the current dose and is now evaluating the next steps, including the design of a pivotal trial for their AAV candidate.

RP-A601, an AAV-based therapeutic, is being developed as a potentially curative treatment for PKP2-ACM, a condition characterized by life-threatening arrhythmias and sudden cardiac death. Current treatments primarily manage symptoms and do not address the underlying genetic cause that this AAV therapy aims to correct. The FDA has granted this AAV gene therapy both fast-track and orphan drug designations.