Rocket Pharmaceuticals Confirms Phase 2 Trial Plans for Danon Disease Gene Therapy With FDA


The study will utilize a pediatric safety run-in that will include 2 patients.

Rocket Pharmaceuticals has come into alignment with the FDA on plans for its pivotal phase 2 clinical trial evaluating RP-A501, an investigational adeno-associated virus vector-based gene therapy intended to treat Danon disease, according to an announcement from the company.1

Specifically, the global, multicenter, single-arm study will seek to recruit 12 patients with Danon disease to be treated with a dose of 6.7x1013 GC/kg of RP-A501. The study will utilize a pediatric safety run-in that will include 2 patients. Improvements in expression of LAMP2, the disease-targeted protein, measured via immunohistochemistry, will serve as a coprimary end point alongside the observed decrease in left ventricular mass. Among the study’s planned secondary end points are a key secondary end point for the change in troponin levels and end points for natriuretic peptide levels, event free survival up to 24 months, treatment-emergent safety events, New York Heart Association (NYHA) class, and responses to Kansas City Cardiomyopathy Questionnaire. The results will be compared to findings from a global natural history study that Rocket is planning to carry out alongside the clinical trial. 

“I am very excited to announce our alignment with the FDA on our pivotal study design for RP-A501 for Danon disease, which reflects the highly collaborative discussions with the review team and senior management at FDA’s Center for Biologics Evaluation and Research and marks the first-ever regulatory pathway to approval for a genetic treatment for heart disease,” Gaurav Shah, MD, the chief executive officer of Rocket Pharma, said in a statement.1 “We believe this milestone sets us on the most efficient and rapid path to delivering this potentially transformative therapy to Danon disease patients who would otherwise progress to heart transplantation or death."

The company noted that it has manufactured enough RP-A501 for the full phase 2 study and that it has developed and qualified potency assays in line with guidance from the FDA. Rocket also reported additional regulatory progress alongside the announcement, pointing out that it has procured an ICD-10 code from the Centers for Medicare and Medicaid Services for LAMP2 deficiency in Danon disease, and that it expects to submit a clinical trial application and investigational medicinal product dossier for the gene therapy in the European Union before the end of Q3 2023.

“I would also like to highlight the work conducted by our chemistry, manufacturing, and controls team over the past several years to establish our in-house current good manufacturing practice manufacturing capabilities, which has already provided us with sufficient material for the pivotal study and should support our eventual commercialization efforts,” Shah continued.1 “As a 1-time potentially curative infusion, RP-A501 has the potential to restore normal cardiac function and provide a lifetime of benefit to patients with Danon disease who have no other viable treatment options. With today’s progress in our Danon disease program, we believe we are forging a path to bring curative gene therapies to patients affected by devastating cardiovascular diseases and broadening the possibilities for addressing the large array of inherited heart diseases through the promise of cardiac gene therapy.”

RP-A501 uses an AAV9 vector to deliver the wildtype human LAMP2B gene and is administered via intravenous infusion. It has previously received regenerative medicine advanced therapy designation from the FDA and priority medicines designation from the European Medicines Agency.2,3

Earlier this year, data from Rocket’s phase 1 clinical trial (NCT03882437) for RP-A501 was presented at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, by coprincipal investigator Joseph Rossano, MD, MS, FAAP, FACC, Jennifer Terker Endowed Chair of pediatric cardiology, and codirector, Cardiac Center, and chief, division of cardiology, Children’s Hospital of Philadelphia.4 Preliminary efficacy data demonstrated LAMP2 expression in all evaluable patients which was mostly sustained with reduced LV mass (14-48% decrease from baseline). Brain natriuretic peptide, troponin, LV wall thickness, and NYHA class improved in all evaluable patients by 12 to 18 months and were sustained for up to 26 months.

1. Rocket Pharmaceuticals reaches FDA alignment on pivotal phase 2 trial design for RP-A501 in Danon disease. News release. Rocket Pharmaceuticals, Inc. September 12, 2023. Accessed September 15, 2023.
2. Rocket Pharmaceuticals receives FDA regenerative medicine advanced therapy (RMAT) designation for RP-A501 gene therapy for Danon disease. News release. Rocket Pharmaceuticals, Inc. February 7, 2023. Accessed September 15, 2023.
3. Rocket Pharmaceuticals receives European Medicines Agency (EMA) priority medicines (PRIME) designation for RP-A501 gene therapy for Danon disease. News release. News release. Rocket Pharmaceuticals, Inc. May 31, 2023. Accessed September 15, 2023.
4. Greenberg B, Rossano J, Taylor M, et al. Danon disease: RP-A501 phase 1 results. The first single-dose intravenous (IV) gene thearpy with recombinant adeno-associated virus (AAV:LAMP2B) for a monogenic cardiomyopathy. Presented at: ASGCT 2023 Meeting, May 16-20, in Los Angeles, California. Abstract #9
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