FDA Lifts Hold on Danon Disease Gene Therapy


Rocket Pharmaceuticals plans to quickly resume the phase 1 trial and commence dosing in their new, low-dose, pediatric cohort in Q3 2021.

The FDA has lifted the clinical hold on Rocket Pharmaceuticals’ RP-A501 gene therapy program to treat Danon disease.1

Rocket Pharmaceuticals met the FDA’s request to amend study protocols and is adding a low dose (6.7e13 vg/kg) pediatric patient cohort. The company plans to resume their non-randomized, open-label phase 1 trial (NCT03882437) of RP-A501 in Q3 2021. They have also removed the high dose cohort from the study. 

“We are grateful for the collaboration between the FDA and our team in reaching agreement on protocol updates allowing us to resume patient enrollment in our Danon disease trial. We look forward to progressing this critical work on behalf of all Danon patients,” said Gaurav Shah, MD, chief executive officer, Rocket Pharmaceuticals, in a statement.1 “We are moving as quickly as possible to resume dosing and commence treatment this quarter.”

RP-A501 consists of a recombinant adeno-associated serotype 9 (AAV9) capsid with a functional version of the human LAMP2B transgene. Prior to the clinical hold, Rocket had announced positive data from the phase 1 trial that showed improvements in immunohistochemistry, brain natriuretic peptide, New York Heart Association Classification, and 6-minute walk test distances over 18 month follow up.2

READ MORE: FDA Places Clinical Hold on Bluebird Bio’s eli-cel for CALD

The trial’s primary outcomes are focused on safety, measured by adverse events (AEs), of a single intravenous infusion of RP-A501, as well as efficacy, which will be assessed by evaluating cardiomyocyte histologic correction and clinical stabilization of cardiomyopathy over 3 years. Secondary outcomes will include further efficacy measures, immunologic responses, heart failure, and survival over 3 years.

The FDA placed the clinical hold on the gene therapy program in May 2021, asking the company to amend study protocols to mitigate risk. The FDA also requested that Rocket adjust patient eligibility to include younger patients with less advanced disease. Phase 1 data had previously revealed that despite promising efficacy data, a serious AE was observed in the high-dose cohort. 

The AE was an immune-related event likely due to complement activation. The patient experienced reversible thrombocytopenia and acute kidney injury which required eculizumab and transient hemodialysis. Kidney function returned to baseline within 3 weeks.3 Following the AE, investigators more closely monitored patients and no additional serious AEs were observed.

“Given the activity observed among young adults in our low-dose cohort, in agreement with the FDA, we are now proceeding with the pediatric cohort. This is another important step forward as we believe the pediatric Danon population has the potential to realize the maximum benefit from our Danon Disease gene therapy program,” Shah added.1

Rocket anticipates reporting updated long-term data from both the low-dose (6.7e13 vg/kg) and higher-dose (1.1e14 vg/kg) young adult cohorts in the fourth quarter of this year. 

1. 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
2. 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
3. Rocket Pharmaceuticals, Inc. Form 10-K 2020. Cranbury, NJ: Rocket Pharmaceuticals, Inc.; 2020. https://www.sec.gov/Archives/edgar/data/1281895/000114036121006677/brhc10020974_10k.htm
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