On May 15, 2025 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of genetic therapies for rare disorders with high unmet need, reported preliminary data from the Phase 1 clinical trial of RP-A601 for the treatment of plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM) (Press release, Rocket Pharmaceuticals, MAY 15, 2025, View Source [SID1234653202]). RP-A601 showed a well-tolerated safety profile with no dose-limiting toxicities, increased PKP2 protein expression, and preliminary indications of improvement or stabilization in arrhythmia burden, heart function, and quality of life in all three patients followed for up to 12 months. Results were presented today as a late-breaking oral presentation at the Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) and will be discussed on a company webinar today at 4:30 p.m. ET.

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"Preliminary data from the Phase 1 study of RP-A601 for PKP2-ACM are highly encouraging, signaling potential clinical benefit along with a generally well-tolerated safety profile," said Gaurav Shah, M.D., Chief Executive Officer of Rocket Pharma. "These initial results represent the second gene therapy from our AAV cardiovascular portfolio to show positive clinical data, propelling us one step closer towards our mission of delivering potentially curative treatments to patients with rare and devastating heart conditions."

The preliminary safety and efficacy of RP-A601 were evaluated in a single-arm, open-label, multi-center Phase 1 study in three patients with PKP2-ACM who received a dose of 8×1013 GC/kg. Initial data from the Phase 1 study (safety cut-off May 6, 2025; efficacy cut-off April 2025) showed that RP-A601 was generally well-tolerated with no dose-limiting toxicities observed in all patients followed for up to 12 months. Most treatment emergent adverse events were mild/moderate in severity and self-limited with only one patient experiencing severe adverse events which resolved without clinical sequelae within two months post-treatment, believed to be associated with the immunomodulatory regimen.

Cardiac biopsies showed RP-A601 increased PKP2 protein expression in all three patients. In the patients with low baseline PKP2 expression (N=2), improvements in PKP2 protein expression relative to total cell protein were approximately 110% and 398%, respectively, from baseline to six months follow-up. In addition, RP-A601 increased protein expression and promoted desmosomal localization of PKP2, Desmocollin-2, and Cadherin-2 in all three patients.

Preliminary indications of improvement or stabilization were observed in arrhythmia burden, heart function, and quality of life. Patients in the Phase 1 trial also demonstrated:

Improvements/stabilization in right ventricular (RV) function.
All patients showed normal RV systolic function at most recent follow-up.
Improvements in quality-of-life as assessed through the Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Class.
Clinical improvement in KCCQ-12 score of 34-41 points (≥5 point increases considered clinically meaningful in adults) and improved NYHA class (from Class II at baseline to Class I; NYHA Class I reflects the absence of clinical signs of heart failure) in both patients followed beyond six months.
Decreased/stabilized ventricular ectopy (premature ventricular contractions [PVC], non-sustained ventricular tachycardia [NSVT]) on rhythm monitoring.
Patients experienced a 9% to 63% reduction in PVCs from baseline evaluated six to 12 months post-treatment.
The only patient who had baseline NSVTs saw a decrease from five to zero NSVT episodes per 24-hour period at six months post-treatment.
Decreased/stabilized T-wave inversions on electrocardiogram (ECG).
One patient saw a reduction in ECG leads with T-wave inversions (precordial and inferior ECG) from six to two at six months post-treatment.
Investor Webcast Information
Company management will host a webinar today, May 15, 2025, at 4:30 p.m. ET. To join the investor webinar, please register at View Source The webcast is available under "Events" in the Investors section of the Company’s website at: View Source The webcast replay will be available on the Rocket website upon completion of the event.

About RP-A601
RP-A601 is an investigational gene therapy for the treatment of plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM). RP-A601 consists of a recombinant adeno-associated serotype rh74 capsid containing a functional version of the human PKP2 transgene (AAVrh74.PKP2) which is administered as a single intravenous (IV) infusion. RP-A601 is being investigated as a one-time, potentially curative gene therapy treatment that may improve survival and quality of life for patients affected by PKP2-ACM. Rocket holds Fast Track designation in the U.S. and Orphan Drug designation in the U.S. and Europe for the program.

About PKP2-Arrhythmogenic Cardiomyopathy (PKP2-ACM)
PKP2-ACM is an inherited heart disease caused by mutations in the PKP2 gene and characterized by life-threatening ventricular arrhythmias, cardiac structural abnormalities, and sudden cardiac death. PKP2-ACM affects approximately 50,000 adults and children in the U.S. and Europe. Patients living with PKP2-ACM have an urgent unmet medical need, as current medical, implantable cardioverter defibrillator (ICD), and ablation therapies do not consistently prevent disease progression or arrhythmia recurrence, are associated with significant morbidity including inappropriate shocks and device and procedure-related complications, and do not address the underlying pathophysiology or genetic mutation.