Rocket’s PKP2-Arrhythmogenic Cardiomyopathy Gene Therapy RP-A601 Improves or Stabilizes Heart Function in Phase 1 Trial
The data presented came from 3 patients treated in the trial who had a follow-up time of up to 12 months.
Rocket Pharmaceuticals’ RP-A601, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat plakophilin-2 related Arrhythmogenic Cardiomyopathy (PKP2-ACM), has demonstrated the ability to stabilize or improve heart function in patients treated in a phase 1 clinical trial (NCT05885412).1 The updated data from the study were presented at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA.
The data presented came from 3 patients treated in the trial who had a follow-up time of up to 12 months. All 3 patients received the same dose of RP-A601, 8x1013 GC/kg. As of the April 2025 data cut off for efficacy, all 3 patients had shown increases in expression of PKP2 protein on cardiac biopsies. Furthermore, 1 of the 2 patients who had low PKP2 expression at baseline showed an increase of approximately 110% in PKP2 relative to total cell protein from baseline to 6 months of follow-up and the other of these 2 patients showed an increase of approximately 398%. Rocket additionally pointed out that in all 3 patients desmosomal localization of PKP2, Desmocollin-2, and Cadherin-2, was promoted by treatment with RP-A601.
Rocket also noted that with regard to arrhythmia burden, heart function, and quality of life, improvement or stabilization was preliminarily suggested by observations in the trial. Normal right ventricular systolic function was seen in all patients at their most recent follow-up. In the 2 patients who were followed for at least 6 months, an improvement of of 34-41 points in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score was reported along with an improvement from New York Heart Association (NYHA) Class II at baseline to Class I. A reduction in premature ventricular contractions of 9% to 63% was observed when evaluated from baseline to 6 to 12 months after treatment. Rocket also stated that at 6 months posttreatment the 1 patient who had nonsustained ventricular tachycardias (NSVTs) achieved a reduction from 5 NSVT episodes per 24-hour period to 0 NSVT episodes per 24-hour period. The company also noted that at 6 months posttreatment 1 patient achieved a decrease in electrocardiogram leads with T-wave inversions from 6 to 2.
With regard to safety, which had a data cut off of May 6, 2025, Rocket characterized the gene therapy product as “generally well tolerated.” There were no dose-limiting toxicities, and treatment-emergent adverse events (AEs) were for the most part mild or moderate and resolved without intervention. A single patient experienced serious AEs that are thought to be related to the immunomodulatory regimen, but these AEs resolved without sequelae by 2 months posttreatment. The company stated that no further dose escalation is planned for the trial.
“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,” Gaurav Shah, MD, the chief executive officer of Rocket Pharma, said in a statement.1 “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 investigational new drug (IND) application for RP-A601's phase 1 trial was originally cleared by the FDA in May 2023 based on preclinical studies that demonstrated decreased arrhythmias and increased survival.2 Notably, it was the first gene therapy for PKP2-ACM to receive IND clearance from the FDA. In June 2023, RP-A601 was granted fast track and orphan drug designations by the FDA.3
“Today’s news is a significant milestone, as we build on our leading cardiovascular gene therapy expertise to advance a historic second program targeting the heart into clinical development, this time for patients with PKP2-ACM who have an urgent need for improved treatment options,” Kinnari Patel, PharmD, MBA, the president and chief operating officer of Rocket Pharma, said in a statement at the time of the IND clearance.2 “RP-A601 offers the potential of a one-time, curative alternative to medical therapy, implantable cardioverter defibrillators, and ablations which are associated with adverse effects, complications, and recurrence of arrhythmias and do not halt the progression of disease. Robust preclinical proof of concept has demonstrated decreased arrhythmias and increased survival. With IND clearance in hand, we are rapidly advancing the first investigational gene therapy for PKP2-ACM into the clinic.”
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