Rocket Snags IND Clearance for BAG3-DCM Gene Therapy Trial

Rocket Pharmaceuticals has received clearance from the FDA of an investigational new drug application (IND) for RP-A701, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat BAG3-associated dilated cardiomyopathy (BAG3-DCM).¹

The IND clearance enables the company to start a first-in-human phase 1 clinical trial for the gene therapy. The multicenter study will take the form of a dose-escalation trial and will enroll adult patients with BAG3-DCM who have an implantable cardioverter defibrillator and advanced disease that puts them at a high risk of heart failure progression and cardiac death. BAG3 protein expression, changes in cardiac biomarkers, and clinical predictors of disease progression will be among the end points evaluated in the study, which will treat each patient with a single dose of the gene therapy product. RP-A701 utilizes an AAVrh.74 vector and constitutes a first-in-class treatment for BAG3-DCM.

“The FDA clearance of RP-A701, our third clinical-stage gene therapy candidate from our AAV cardiovascular portfolio, is an important milestone for Rocket,” Kinnari Patel, PharmD, MBA, the president, head of R&D, and chief operating officer at Rocket Pharma, said in a statement.¹ “With programs 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.”

In addition to RP-A701, Rocket is developing other cardiovascular gene therapy products, including RP-A501, an investigational AAV9 vector-based gene therapy intended to treat Danon disease, and RP-A601, an investigational AAV vector-based gene therapy intended to treat plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM).^2,3 In May of this year, Rocket announced that a patient had passed away after treatment with RP-A501 in the context of a pivotal phase 2 clinical trial (NCT06092034). The patient’s death occurred after an acute systemic infection and was associated with an unexpected serious adverse event (SAE) of clinical complications related to a capillary leak syndrome. Rocket stated that dosing in the trial was paused when it became aware of the SAE and that the FDA put a clinical hold on the trial on May 23, 2025, to enable continued evaluation of the event.

“We are heartbroken by this loss and are fully committed to our mission to develop gene therapies that address the underlying cause of devastating diseases like Danon,” Gaurav Shah, MD, the chief executive officer of Rocket Pharmaceuticals, said in a May 2025statement.² “We are immensely grateful for the patients and families who participate in this important research.”

Earlier in May 2025, data from a phase 1 clinical trial (NCT05885412) evaluating RP-A601 for PKP2-ACM were presented at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA.³ The data presented came from 3 patients treated in the trial who had a follow-up time of up to 12 months. Rocket noted that with regard to arrhythmia burden, heart function, and quality of life, improvement or stabilization was preliminarily suggested by observations in the trial and normal right ventricular systolic function was seen in all patients at their most recent follow-up.

“Preliminary data from the phase 1 study of RP-A601 for PKP2-ACM are highly encouraging, signaling potential clinical benefit along with a generally well-tolerated safety profile,” Shah said in a statement at the time.³ “These initial results represent the second gene therapy from our AAV cardiovascular portfolio to show positive clinical data, propelling us one step closer towards our mission of delivering potentially curative treatments to patients with rare and devastating heart conditions.”

REFERENCES
1. Rocket Pharmaceuticals announces FDA IND clearance of RP-A701 for the treatment of BAG3-associated dilated cardiomyopathy. News release. Rocket Pharmaceuticals, Inc. June 30, 2025. Accessed July 2, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-announces-fda-ind-clearance-rp-a701
2. Rocket Pharmaceuticals provides update on phase 2 clinical trial of RP-A501 for Danon disease. News release. Rocket Pharmaceuticals, Inc. May 27, 2025. Accessed July 2, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-provides-update-phase-2-clinical-trial-rp
3. Rocket Pharmaceuticals presents preliminary data from phase 1 clinical trial of RP-A601 for PKP2 arrhythmogenic cardiomyopathy at 28th annual meeting of the American Society of Gene and Cell Therapy. News release. Rocket Pharmaceuticals, Inc. May 15, 2025. Accessed July 2, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-presents-preliminary-data-phase-1