Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a leading biotechnology company focused on developing genetic therapies for rare, life-threatening diseases, announced promising long-term safety and efficacy data from its Phase 1 RP-A501 study. The results were presented at the 2024 American Heart Association (AHA) Scientific Sessions and published in The New England Journal of Medicine (NEJM). The data showed that RP-A501, an investigational gene therapy for Danon disease, was well tolerated and led to sustained cardiac LAMP2 protein expression and a ≥10% reduction in left ventricular (LV) mass index at 12 months, with benefits lasting up to 60 months.
“Today’s data publication in NEJM and presentation at AHA represent a major milestone, demonstrating for the first time that AAV-based gene therapy can achieve long-term efficacy in treating a cardiac disease. This marks the most comprehensive dataset for any cardiac gene therapy,” said Gaurav Shah, M.D., CEO of Rocket Pharma. “When gene therapy works, it can be life-changing, and these results suggest RP-A501 could offer a transformative option for patients with Danon disease.”
Phase 1 Study Overview
The Phase 1 trial was a single-arm, open-label, multi-center study assessing the safety, tolerability, and efficacy of RP-A501 in male patients with Danon disease. A total of seven patients (pediatric and adult/adolescent) were treated with a single intravenous infusion of RP-A501, with doses ranging from 6.7 x 10¹³ GC/kg to 1.1 x 10¹⁴ GC/kg.
The results showed that RP-A501, in combination with a transient immunomodulatory regimen, was generally well tolerated. Most adverse events (AEs) were mild or moderate and unrelated to the gene therapy. Importantly, all AEs were manageable or reversible. One patient, who had severe heart failure at baseline, required a heart transplant five months post-treatment.
Key Efficacy Findings
Efficacy assessments at multiple time points revealed significant improvements in key clinical parameters:
- Cardiac LAMP2 Protein Expression: All patients demonstrated expression of the LAMP2 protein in the heart at 12 months, with sustained expression up to 60 months in some cases.
- Reduction in LV Mass Index: Median reduction in LV mass index was 24%, surpassing the co-primary endpoint of ≥10% reduction for the ongoing Phase 2 trial.
- Preserved Cardiac Function: Most patients maintained normal left ventricular ejection fraction (LVEF).
- Reduction in Cardiac Biomarkers: Median reductions of 84% in cardiac troponin I (cTnI) and 57% in NT-proBNP, indicating improved cardiac function.
- NYHA Class Improvement: Most patients improved from baseline New York Heart Association (NYHA) Class II to Class I, indicating reduced heart failure symptoms.
- Quality of Life: Median improvement of 27 points in Kansas City Cardiomyopathy Questionnaire scores, sustained for up to 54 months.
- Long-Term Follow-Up: Preliminary data for one patient at the 5-year mark showed Grade 3 LAMP2 expression in heart tissue.
Investigator’s Perspective
“The long-term safety and efficacy results in this study provide strong evidence for the potential of RP-A501 in treating Danon disease, a condition for which there are currently no approved therapies,” said Barry H. Greenberg, MD, FHFSA, Distinguished Professor of Medicine at UC San Diego School of Medicine and the principal investigator of the Phase 1 study. “While heart transplantation is an option, it is not curative, and this data offers hope for a new, potentially transformative approach.”
RP-A501: A Breakthrough in Gene Therapy for Danon Disease
RP-A501 is Rocket’s gene therapy designed to treat Danon disease, a rare genetic disorder caused by mutations in the LAMP2 gene. This disorder leads to severe heart failure, often resulting in premature death in affected males. RP-A501 uses an adeno-associated virus (AAV9) to deliver a functional version of the LAMP2B gene to heart muscle cells, addressing the root cause of the disease.
The therapy is administered as a single intravenous infusion, and preclinical and clinical data indicate that RP-A501 is well tolerated and effectively targets cardiomyocytes, improving cardiac structure and function.
Next Steps and Ongoing Trials
Encouraged by the long-term results, Rocket Pharmaceuticals plans to continue advancing RP-A501 through clinical development. The ongoing Phase 2 pivotal trial will further assess the therapy’s efficacy, with co-primary endpoints of LV mass index reduction and cardiac protein expression.
RP-A501 is also being investigated for other cardiovascular conditions, including PKP2-Arrhythmogenic Cardiomyopathy (ACM) and BAG3-Dilated Cardiomyopathy (DCM), expanding its potential impact across cardiac diseases.
Investor Webcast and Additional Information
Rocket Pharmaceuticals will host a 30-minute investor webcast on November 18, 2024, at 12:00 p.m. ET to discuss the data and answer questions. The webcast can be accessed here, and the replay will be available on the company’s investor relations website.
About Rocket Pharmaceuticals
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is a fully integrated, late-stage biotechnology company advancing a pipeline of innovative gene therapies targeting rare, devastating disorders. With a multi-platform approach, Rocket aims to create transformative therapies that address the root cause of genetic diseases, offering hope for patients with high unmet medical needs.
