Rocket’s PKP2-Arrhythmogenic Cardiomyopathy Gene Therapy RP-A601 Snags RMAT Designation

Rocket Pharmaceuticals’ RP-A601, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat plakophilin-2 related arrhythmogenic cardiomyopathy (PKP2-ACM), has received regenerative medicine advanced therapy (RMAT) designation from the FDA.¹

According to Rocket, the RMAT designation was granted based on results from a phase 1 clinical trial (NCT05885412) evaluating RP-A601. Notably, the gene therapy has previously received fast track designation and orphan drug designation (ODD) from the FDA and ODD from the European Commission.

“The FDA’s RMAT designation for RP-A601 represents a meaningful advancement for Rocket and for patients living with PKP2-ACM, a life-threatening genetic heart disease characterized by ventricular arrhythmias and sudden cardiac death,” Kinnari Patel, PharmD, MBA, the president and head of R&D at Rocket Pharmaceuticals, said in a statement.¹ “This marks the fifth RMAT designation in our history and underscores our commitment to developing potentially curative gene therapies for patients with rare and inherited cardiovascular diseases. The early clinical data for RP-A601 are highly encouraging, and we look forward to continued collaboration with the FDA throughout the program’s development.”

Data from the phase 1 trial were presented earlier this year at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, Louisiana.² The data presented came from 3 patients treated in the trial who had a follow-up time of up to 12 months. At the time of the efficacy data cut, increases in expression of PKP2 protein on cardiac biopsies were observed for all 3 patients. In addition, 1 of the 2 patients who had low PKP2 expression at baseline showed an increase of approximately 110% in PKP2 relative to total cell protein from baseline to 6 months of follow-up, and the other of these 2 patients showed an increase of approximately 398%. Preliminary suggestion of improvement or stabilization in arrhythmia burden, heart function, and quality of life was also present in the study’s findings.

Rocket characterized the gene therapy product as “generally well tolerated” in terms of safety, and no dose-limiting toxicities occurred. The company pointed out that for the most part, treatment-emergent adverse events (AEs) were mild or moderate and resolved without intervention, although a single patient experienced serious AEs, which resolved without sequelae by 2 months posttreatment, that were thought to be related to the immunomodulatory regimen.

“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,” Gaurav Shah, MD, the chief executive officer of Rocket Pharma, said in a May 2025 statement.² “These initial results represent the second gene therapy from our AAV cardiovascular portfolio to show positive clinical data, propelling us 1 step closer towards our mission of delivering potentially curative treatments to patients with rare and devastating heart conditions.”

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-A701, an investigational AAV vector-based gene therapy intended to treat BAG3-associated dilated cardiomyopathy (BAG3-DCM).^3,4 The company is also developing marnetegragene autotemcel (RP-L201, to be marketed as Kresladi), a genetically modified autologous hematopoietic stem cell therapy intended to treat leukocyte adhesion deficiency-I (LAD-I).⁵ Notably, on July 24, 2025, Rocket announced that as part of a strategic reorganization, it would be prioritizing the aforementioned therapies over several other therapeutic candidates in its pipeline and cutting its staff by around 30%.

“We are grateful for the remarkable contributions of our entire team and the significant progress we've made in advancing genetic therapies for rare diseases,” Shah said in the press release announcing the reorganization.⁵ “Our prioritization reflects a commitment to the programs with the most compelling near-term opportunities for patients and to setting a foundation for Rocket’s long-term growth and success. Together, our cardiovascular programs have demonstrated strong potential for impact in areas of high unmet need in substantial patient populations.”

REFERENCES
1. Rocket Pharmaceuticals receives FDA regenerative medicine advanced therapy (RMAT) designation for RP-A601 gene therapy for PKP2-arrhythmogenic cardiomyopathy. News release. Rocket Pharmaceuticals Inc. July 17, 2025. Accessed July 29, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-receives-fda-regenerative-medicine-3
2. 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 29, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-presents-preliminary-data-phase-1
3. 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 29, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-provides-update-phase-2-clinical-trial-rp
4. 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 29, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-announces-fda-ind-clearance-rp-a701
5. Rocket Pharmaceuticals announces strategic corporate reorganization and pipeline prioritization of cardiovascular programs. News release. Rocket Pharmaceuticals, Inc. July 17, 2025. Accessed July 29, 2025. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-receives-fda-regenerative-medicine-3