RP-A501 / Rocket Pharma - LARVOL DELTA

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

Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease. (PubMed, N Engl J Med) - P1 | "A single infusion of RP-A501 appeared to be safe and was associated with cardiac LAMP2 expression and evidence of clinical improvement over a period of 24 to 54 months. (Funded by Rocket Pharmaceuticals; ClinicalTrials.gov number, NCT03882437.)."

Gene therapy • Journal • P1 data • Acute Kidney Injury • Cardiomyopathy • Cardiovascular • Complement-mediated Rare Disorders • Congestive Heart Failure • Gene Therapies • Heart Failure • Hematological Disorders • Myositis • Nephrology • Renal Disease • Thrombocytopenia • Transplantation • LAMP2 • TNNI3

Danon Disease Phase 1 RP-A501 Results: The First Single-Dose Intravenous Gene Therapy with Recombinant Adeno-Associated Virus (AAV9:LAMP2B) for a Monogenic Cardiomyopathy (AHA 2024) - P1 | "Immunomodulation (IM): 2-3m prednisone, tacrolimus/sirolimus, and rituximab. RP-A501 was associated with acceptable safety and conferred sustained myocardial LAMP2 expression, with stabilized and largely improved serologic, echocardiographic, and clinical CMP parameters. In contrast to demonstrated rapid decline and early mortality in DD, all pts are alive and 6/6 evaluable pts are NYHA Class I at 24-54m follow-up."

Gene therapy • P1 data • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Immunology • Myositis • Pediatrics • Renal Disease • AVEN • LAMP2

Discussant: Danon Disease Phase 1 RP-A501 (AHA 2024) - No abstract available

P1 data • Cardiomyopathy • Cardiovascular

NEJM at AHA - Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease. (PubMed, N Engl J Med) - No abstract available

Gene therapy • Journal • P1 data • Gene Therapies

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

A Gene Therapy Study of RP-A501 in Male Patients With Danon Disease (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Rocket Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • LAMP2

A Multi-Center, Open Label Gene Therapy Study of RP-A501 in Male Patients With Danon Disease (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Rocket Pharmaceuticals Inc.

Gene therapy • New P2 trial • Gene Therapies • LAMP2

Phase 1 Danon Disease Results: The First Single Dose Intravenous (IV) Gene Therapy (RP-A501) With Recombinant Adeno-Associated Virus (AAV9:LAMP2B) for a Monogenic Cardiomyopathy (AHA 2022) - "Immunomodulation (IM) included prednisone and rituximab, with additional sirolimus for the most recently treated pediatric pts. Results from this phase 1 trial in DD demonstrate that B- and T-lymphocyte directed immunomodulation enables safe IV RP-A501 gene therapy administration, resulting in cardiomyocyte transduction, LAMP2B expression, improved autophagy, and improved/stabilized serologic, echocardiographic and clinical parameters associated with survival in HCM. Updated results will be presented."

Gene therapy • P1 data • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Gene Therapies • Hypertrophic Cardiomyopathy • Pediatrics • Transplantation • LAMP2

Danon Disease Phase 1 RP-A501 Results: The First Single-Dose Intravenous (IV) Gene Therapy with Recombinant Adeno-Associated Virus (AAV9:LAMP2B) for a Monogenic Cardiomyopathy (ASGCT 2023) - P=N/A | "Transient immunomodulation (IM) included prednisone, rituximab, and sirolimus (for the most recently treated pediatric pts).  Between June 2019 and March 2022, 7 males (5 adult, 2 pediatric) with DD age 11.7 - 21.1y (median 18.3y) received RP-A501 (N=5 low dose and N=2 high dose). Results from this phase 1 trial in DD demonstrate that B- and T-lymphocyte directed immunomodulation enables safe IV RP-A501 gene therapy administration, resulting in cardiomyocyte transduction, LAMP2B expression, improved autophagy, and improved/stabilized serologic, echocardiographic and clinical parameters associated with prognosis in HCM. These data support activation of a phase 2 clinical trial."

Gene therapy • P1 data • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Hypertrophic Cardiomyopathy • Immune Modulation • Immunology • Pediatrics • Renal Disease • Transplantation • LAMP2

"Reminding us with the results of the phase I of RP-A501 in Danon" (@MasriAhmadMD)

P1 data

Danon disease phase 1 RP-A501 results: the first single-dose intravenous (IV) gene therapy with recombinant adeno-associated virus (AAV9:LAMP2B) for a monogenic cardiomyopathy (HEART FAILURE 2023) - No abstract available

Gene therapy • P1 data • Cardiomyopathy • Cardiovascular

Gene Therapy for Male Patients With Danon Disease (DD) Using RP-A501; AAV9.LAMP2B (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: Rocket Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting | N=10 ➔ 7 | Trial completion date: Oct 2024 ➔ Mar 2025 | Trial primary completion date: Oct 2022 ➔ Mar 2025

Enrollment change • Enrollment closed • Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • LAMP2

Safety Profile Of The First Pediatric Cardiomyopathy Gene Therapy Trial: RP-A501 (AAV9:LAMP2B) For Danon Disease (HFSA 2022) - No abstract available

Clinical • Cardiomyopathy • Cardiovascular • Gene Therapies • Pediatrics

Extended Results from First-in-Human Clinical Trial of RP-A501 (AAV9:LAMP2B) Gene Therapy Treatment for Danon Disease (ASGCT 2022) - "This ongoing first-in-human trial demonstrates that RP-A501 gene therapy for DD was generally well-tolerated and confers cardiac LAMP2B gene expression. Patients exhibited improvements in multiple cardiac and clinical parameters. Initial pediatric safety results will be presented at the meeting."

Clinical • P1 data • Acute Kidney Injury • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Hematological Disorders • Myositis • Nephrology • Pediatrics • Renal Disease • Thrombocytopenia • Transplantation • NPPB