First clinical gene therapy program for PKP2-ACM, a devastating inherited heart disease affecting approximately 50,000 people in the U.S. and EU

Robust preclinical proof of concept studies showed RP-A601 decreased arrhythmias and increased survival in the PKP2 knockout mouse model

Initiating Phase 1 trial start-up activities and rapidly working towards first patient treatment

CRANBURY, NJ, USA I May 09, 2023 IRocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a leading late-stage biotechnology company advancing an integrated and sustainable pipeline of genetic therapies for rare disorders with high unmet need, today announced that it has received clearance from the U.S. Food and Drug Administration (FDA) for the Company’s Investigational New Drug (IND) application for RP-A601, an AAV.rh74-based gene therapy candidate for the treatment of arrhythmogenic cardiomyopathy due to plakophilin 2 pathogenic variants (PKP2-ACM) a devastating inherited heart disease that can lead to life-threatening arrhythmias, cardiac structural abnormalities, and sudden cardiac death. The current standard of care for patients with PKP2-ACM consists of medical therapy, implantable cardioverter defibrillators (ICDs), and ablations, which are not curative. Even with treatment, life-threatening arrhythmias and progression of disease may still occur. PKP2-ACM affects approximately 50,000 people in the U.S. and Europe.

“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,” said Kinnari Patel, PharmD, MBA, President and Chief Operating Officer, Rocket Pharma. “RP-A601 offers the potential of a one-time, curative alternative to medical therapy, ICDs, 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.”

The multi-center Phase 1, dose escalation trial will evaluate the safety and preliminary efficacy of RP-A601 in at least six adult PKP2-ACM patients with ICDs and overall high risk for arrhythmias. The study will assess the impact of RP-A601 on PKP2 myocardial protein expression, cardiac biomarkers, and clinical predictors of life-threatening ventricular arrhythmias and sudden cardiac death. Patients in the dose-escalation trial will receive a single dose of RP-A601. The starting dose will be 8 x 1013 GC/kg. The rh74 serotype used in RP-A601 was selected based on a favorable safety profile in gene therapy clinical development programs for other diseases and overall favorable benefit-risk profile in extensive preclinical RP-A601 studies.

RP-A601 Development Highlights

  • A partnership between Rocket and leading scientific collaborators at NYU Grossman School of Medicine resulted in vigorous and translationally relevant animal models and preclinical studies. These studies showed that RP-A601 decreased arrhythmias, improved right ventricular morphology and function, and increased survival in PKP2 knockout mice. Scientific collaborators include Mario Delmar, M.D., Ph.D., Patricia and Robert Martinsen Professor of Cardiology and Marina Cerrone, M.D., Research Associate Professor, Co-Director, Inherited Arrhythmia Clinic.
  • GMP drug product manufacturing has been completed, and a potency assay has been both developed and qualified.
  • A robust clinical protocol has been developed, vetted by an advisory board comprised of experts in PKP2-ACM and gene therapy clinical development and informed by insights from the patient community.
  • Natural history studies are planned to provide additional context for the Phase 1 trial.
  • Initial clinical sites for the Phase 1 trial have been selected. Principal Investigators include Barry Greenberg, M.D., FHFSA, Director of the Advanced Heart Failure Treatment Program at University of California, San Diego Medical Center and Joseph Rossano, M.D., M.S., FAAP, FACC, Co-Director of the Cardiac Center and Chief of the Division of Cardiology at Children’s Hospital of Philadelphia.
  • Rocket is initiating Phase 1 study start-up activities and rapidly working towards first patient treatment.

Preclinical data from the RP-A601 program will be presented as a late-breaking abstract at the 26th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) on Friday, May 19, 2023, 8:00 a.m. – 9:45 a.m. PT. More information can be found here.

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. 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 this devastating disease.

About Rocket Pharmaceuticals, Inc.

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is advancing an integrated and sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare disorders. The Company’s platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket’s clinical programs using lentiviral vector (LV) based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD), a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Rocket’s first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon Disease, a devastating, pediatric heart failure condition. Rocket also has preclinical AAV-based gene therapy programs in PKP2-arrhythmogenic cardiomyopathy (ACM) and BAG3-associated dilated cardiomyopathy (DCM). For more information about Rocket, please visit

SOURCE: Rocket Pharmaceuticals