Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a biotechnology company advancing a pipeline of genetic therapies for rare disorders with high unmet need, has received clearance from the U.S. Food and Drug Administration (FDA) for the company’s Investigational New Drug (IND) application for RP-A701, an AAVrh.74-based gene therapy candidate for the treatment of BAG3-associated dilated cardiomyopathy (BAG3-DCM), a severe form of heart failure characterized by progressive ventricular enlargement and impaired systolic function.
“The FDA clearance of RP-A701, our third clinical-stage gene therapy candidate from our AAV cardiovascular portfolio, is an important milestone for Rocket,” said Kinnari Patel, president, head of R&D and chief operating officer of Rocket Pharma.
“With programmes in the clinic for each of the major types of genetic cardiomyopathies – hypertrophic, dilated, and arrhythmogenic – we are advancing our mission to bring potentially curative gene therapies to patients with rare and life-threatening cardiovascular diseases. Phase 1 trial start-up activities are currently underway for RP-A701, and we are working towards treating the first patient.”
The first-in-human phase 1 clinical trial will be a multi-center, dose-escalation study designed to evaluate the safety, biological activity, and preliminary efficacy of RP-A701 in adults with BAG3-DCM. Initial study participants will include adults with implantable cardioverter defibrillators (ICDs) and advanced disease at high risk for heart failure progression and cardiac death. Participants will receive a single dose of RP-A701, and the trial will assess BAG3 protein expression, changes in cardiac biomarkers, and clinical predictors of disease progression.
BAG3-associated dilated cardiomyopathy
BAG3-DCM is an inherited heart disease caused by mutations in the BAG3 gene (Bcl2-associated athanogene 3) resulting in early onset, rapidly progressing heart failure, and significant morbidity and mortality.
The BAG3 protein contributes to multiple cellular functions, including cardiac contractility, protein quality control (as a co-chaperone), cardiomyocyte structural support, and regulation of autophagy and apoptosis. Loss of BAG3 leads to an accumulation of misfolded and damaged proteins, which can impair the heart’s ability to contract, leading to impaired cardiac function, heart failure, and even premature death. The prevalence of BAG3-associated DCM in the US is as many as 30,000 individuals.
Patients living with BAG3-DCM have an urgent unmet medical need, as current medical and interventional therapies (including implantable cardioverter defibrillator [ICD], cardiac resynchronisation devices, and heart transplant) do not consistently prevent disease progression, are associated with significant morbidity including inappropriate ICD shocks and device, procedure, and transplant-related complications, and do not address the underlying pathophysiology or genetic mutation.
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