Danon Disease Gene Therapy Granted RMAT Designation by FDA


A pivotal phase 2 clinical trial for RP-A501 is expected to initiate in Q2 2023.

Rocket Pharmaceuticals’ RP-A501, an investigational adeno-associated serotype 9 (AAV9) vector-based gene therapy being evaluated in a phase 1 clinical trial (NCT03882437) for Danon disease, has received regenerative medicine advanced therapy (RMAT) designation from the FDA.1

A pivotal phase 2 clinical trial for RP-A501 is expected to initiate in the second quarter of this year. Rocket Pharmaceuticals has announced that the trial will likely follow a single arm, open-label approach and include a biomarker-based composite end point and a natural history comparator. The company also noted in January of this year that it has produced AAV current Good Manufacturing Practice batches with improved product specifications compared to the phase 1 product.2 RP-A501 was previously granted orphan drug designation and rare pediatric disease designation.1

“Today’s exciting RMAT designation demonstrates recognition from the FDA of the early meaningful benefit of RP-A501 in Danon disease and its potential to deliver lifesaving treatment for patients...” Gaurav Shah, MD, chief executive officer, Rocket Pharma, said in a statement regarding the news.1 “RP-A501 is the first cardiac gene therapy to receive RMAT designation from the FDA, and today’s news is another important step forward both for patients with Danon Disease and for the gene therapy field.”

In January 2023, Rocket Pharmaceuticals announced that the company had shared updated data from RP-A501's open-label, multicenter phase 1 clinical trial with the FDA.2 It was noted that the data showed durable improvements and stabilization in all biomarker and clinical end points. Improvements in brain natriuretic peptide (BNP) and New York Heart Association (NYHA) class, which contrasted with the increased BNP levels and worsening NYHA class seen in natural history sample data, were highlighted. The company additionally noted that improvements were observed in protein expression, reduced autophagic vacuoles, troponin, left ventricular mass and thickness, and Kansas City Cardiomyopathy Questionnaire scores.

Safety and efficacy data from the trial were previously presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2022.3 At the time, it was noted that RP-A501 was generally well-tolerated in the low-dose pediatric cohorts and adult cohorts. In 2021, Rocket ceased enrollment in the high-dose cohort of the study following a clinical hold placed by the FDA in relation to a serious adverse event seen in that cohort.4,5

CGTLive spoke with Joseph Rossano, MD, MS, FAAP, FACC, chief, Division of Cardiology, Children's Hospital of Philadelphia, who presented the data at HFSA, in an October 2022 interview. 

“Potentially, a gene therapy for this disorder can be a real game changer,” Rossano said in the interview. “In the current state, there really is no effective medical therapy. We have medicines that can hopefully help treat symptoms of heart failure and can treat arrhythmias. But we have no therapies that alter the natural history of the disease. And so what's really exciting about this therapy is that it offers the prospect and the hope of dramatically changing the natural history.”

1. 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 February 7, 2023.https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-receives-fda-regenerative-medicine-1 
2. Rocket Pharmaceuticals expands cardiac gene therapy portfolio with addition of RP-A601 for PKP2-ACM and announces positive updated phase 1 data for RP-A501 in Danon disease. News release. Rocket Pharmaceuticals, Inc. January 9, 2023. Accessed February 7, 2023. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-expands-cardiac-gene-therapy-portfolio 
3. Rocket Pharmaceuticals announces positive updates from phase 1 clinical trial for RP-A501 in Danon disease at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2022. News release. Rocket Pharmaceuticals. September 30, 2022. https://www.businesswire.com/news/home/20220930005139/en/%C2%A0Rocket-Pharmaceuticals-Announces-Positive-Updates-from-Phase-1-Clinical-Trial-for-RP-A501-in-Danon-Disease-at-the-Heart-Failure-Society-of-America-HFSA-Annual-Scientific-Meeting-2022 
4. Rocket Pharmaceuticals announces FDA lifts clinical hold on Danon disease trial of RP-A501. News release. Rocket Pharmaceuticals. August 16, 2021. https://www.businesswire.com/news/home/20210816005160/en/Rocket-Pharmaceuticals-Announces-FDA-Lifts-Clinical-Hold-on-Danon-Disease-Trial-of-RP-A501
5. Rocket Pharmaceuticals reports first quarter 2021 financial results and highlights recent progress. News release. Rocket Pharmaceuticals. May 10, 2021. https://ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-reports-first-quarter-2021-financial 
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