RP-A601 / Rocket Pharma - LARVOL DELTA

Preliminary Data from a Phase I Gene Therapy Trial of RP-A601 (AAVrh.74-PKP2a) for Adult Patients with PKP2-Arrhythmogenic Cardiomyopathy (PKP2-ACM) (ASGCT 2025) - P1 | "Initial results from this on-going phase I trial show treatment with RP-A601 was well-tolerated and conferred increased cardiac PKP2a expression in patients afflicted with this life-threatening and highly morbid disorder. Pending confirmation, these results represent the first demonstration of AAV-mediated genetic modification of an inherited ACM or any disorder predisposing to sudden cardiac death. Updated results will be presented."

Clinical • Gene therapy • Late-breaking abstract • P1 data • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Gene Therapies • Heart Failure • Immunology • Infectious Disease • Pancreatitis • Septic Shock • Ventricular Tachycardia

AAV Gene Therapies for Debilitating Inherited Cardiomyopathies (ISHLT 2025) - "AAV-mediated gene therapies can restore expression of essential proteins, impaired in inherited disorders, leading to improvement in cardiac structure, function, and survival.Methods Preclinical and Phase 1 data have demonstrated robust safety and preliminary efficacy of RP-A501 (AAV9.LAMP2B) in Danon disease including LAMP2B protein expression, ventricular wall thickness, and survival. Preclinical studies of RP-A601 (AAVrh.74-PKP2a) have demonstrated PKP2 protein expression, arrhythmia reduction, improvement in cardiac histology and structure, and survival in a PKP2-deficient animal model of ACM...Efforts to minimize and address potential risks of systemic AAV infusions include the use of an immunomodulating regimen and active monitoring.Conclusion AAV-based gene therapies offer potential to deliver unprecedented clinical benefit in patients with Danon disease, PKP2-ACM, and BAG3-associated DCM. Timely and comprehensive use of genetic testing is vital for definitive..."

Gene therapy • Cardiomyopathy • Cardiovascular • Gene Therapies • BAG3 • LAMP2

AAV Gene Therapies For Serious Inherited Cardiomyopathies (HFSA 2024) - "This single arm study involves a single intravenous infusion of RP-A501 with a primary endpoint including improvement in LAMP2 protein expression and reduction in ventricular hypertrophy. RP-A601 is being evaluated in a multi-center, open-label, dose escalation trial as a single intravenous infusion in adult patients (age ≥18 years) with clinical (2010 revised Task Force Criteria) and genetic diagnosis of PKP2-ACM and an implanted ICD...This single arm study involves a single intravenous infusion of RP-A501 with a primary endpoint including improvement in LAMP2 protein expression and reduction in ventricular hypertrophy. RP-A601 is being evaluated in a multi-center, open-label, dose escalation trial as a single intravenous infusion in adult patients (age ≥18 years) with clinical (2010 revised Task Force Criteria) and genetic diagnosis of PKP2-ACM and an implanted ICD... Scientific advances in AAV-based gene therapies offer potential to deliver unprecedented clinical..."

Gene therapy • Cardiomyopathy • Cardiovascular • Gene Therapies • BAG3 • LAMP2

AAV Gene Therapies for Serious Inherited Cardiomyopathies (AAP-NCE 2024) - "Preclinical studies have shown that RP-A601 (AAV serotype rh.74 vector containing the human plakophilin-2a transgene, AAVrh.74-PKP2a) has enabled expression of PKP2 protein, reduction of arrhythmia, improvement in cardiac histology and structure, and survival in a PKP2-deficient animal model of ACM. The development of RP-A501 has successfully progressed to a global multi-center Phase 2 trial that is currently enrolling male patients age ≥ 8 years with pathologic or likely pathologic genetic variants of Danon disease. Scientific advances in AAV-based gene therapies offer potential to deliver unprecedented clinical benefit in patients with Danon disease and PKP2-ACM. Timely and comprehensive use of genetic testing is vital for definitive diagnosis and directing targeted treatment developments."

Gene therapy • Cardiomyopathy • Cardiovascular • Gene Therapies • Pediatrics • LAMP2

Phase I gene therapy clinical trial design of RP-A601 in adult patients with PKP2-arrhythmogenic cardiomyopathy (PKP2-ACM) (ESC 2024) - P1 | "PKP2-ACM is a devastating disease associated with high morbidity and mortality. This Phase I trial will evaluate the safety and preliminary efficacy of RP-A601 and was initiated based on robust preclinical efficacy and safety data."

Clinical • Gene therapy • P1 data • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Preclinical efficacy & safety of AAVrh.74‐PKP2a (RP‐A601): gene therapy for PKP2‐associated arrhythmogenic cardiomyopathy (ESGCT 2023) - "Clinical pathology and histopathology analyses revealed that AAVrh.74-PKP2a was well tolerated and safe across multiple studies up to (and including) doses of 3 × 1014 vg/kg.Collectively, the preclinical efficacy and safety package strongly support the clinical development of RP-A601 as a potential therapeutic in patients with PKP2-ACM. The IND package was endorsed by the FDA in May 2023 and activity supporting initiation of a first-in-human clinical trial is ongoing."

Gene therapy • Preclinical • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Fibrosis • Gene Therapies • Immunology • Transplantation

AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans. (PubMed, Circ Genom Precis Med) - "Experiments were performed using a PKP2-cKO (cardiac-specific, tamoxifen-activated deletion of plakophilin-2). Importantly, the therapeutic benefit was shown in mice receiving AAVrh.74-PKP2a after disease onset. These preclinical data demonstrate the potential for AAVrh.74-PKP2a (RP-A601) as a therapeutic for PKP2-related arrhythmogenic right ventricular cardiomyopathy in both early and more advanced stages of the disease."

Gene therapy • Journal • Preclinical • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure

A Phase 1, Dose Escalation Trial of RP-A601 in Subjects With PKP2 Variant-Mediated Arrhythmogenic Cardiomyopathy (PKP2-ACM) (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Rocket Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: May 2025 ➔ Sep 2025

Enrollment open • Trial completion date • Trial primary completion date • Cardiomyopathy • Cardiovascular

Rocket Pharmaceuticals Reports Second Quarter 2023 Financial Results and Highlights Recent Progress (Businesswire) - "Rocket Pharmaceuticals, Inc...today reported financial results for the quarter ending June 30, 2023, and updates from the Company’s key pipeline developments, business operations and upcoming milestones...Positive proof of concept from preclinical studies of RP-A601 presented at the ASGCT Annual Meeting. Data demonstrated decreased arrhythmias and increased survival in the PKP2 knockout mouse model...BLA submission for RP-L102 anticipated in Q4 2023....Cash, cash equivalents and investments as of June 30, 2023, were $307.0 million."

BLA • Commercial • Preclinical • Cardiomyopathy • Cardiovascular

Rocket Pharmaceuticals Receives FDA Fast Track and Orphan Drug Designations for RP-A601 Gene Therapy for PKP2 Arrhythmogenic Cardiomyopathy (ACM) (Businesswire) - "Rocket Pharmaceuticals...today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track and Orphan Drug designations to RP-A601, the Company’s gene therapy candidate for the treatment of plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM)....Fast Track designation is granted to facilitate the development and expedite the review of medicines that treat serious conditions and fill an unmet medical need....Orphan Drug designation is granted to support the development of medicines for rare disorders that affect fewer than 200,000 patients in the U.S."

Fast track designation • Orphan drug • Cardiomyopathy • Cardiovascular

A Phase 1, Dose Escalation Trial of RP-A601 in Subjects With PKP2 Variant-Mediated Arrhythmogenic Cardiomyopathy (PKP2-ACM) (clinicaltrials.gov) - P1 | N=9 | Not yet recruiting | Sponsor: Rocket Pharmaceuticals Inc.

New P1 trial • Cardiomyopathy • Cardiovascular