AAV-based gene therapeutic / 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

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