Topline Findings
- FDA lifts clinical hold on RP-A501 trial: Rocket Pharmaceuticals’ pivotal Phase II study for Danon disease resumes less than three months after the hold.
- Revised dosing and safety strategy: The trial will continue with a lower 3.8 x 10¹³ GC/kg dose and an updated immunomodulatory regimen to enhance patient safety.
- Gene therapy advances for rare cardiac disorder: RP-A501 remains the first investigational gene therapy for a cardiovascular condition with FDA designations that include RMAT, Fast Track, Rare Pediatric, and Orphan Drug.
The FDA has lifted the clinical hold on Rocket Pharmaceuticals’ pivotal Phase II trial (NCT06092034) of RP-A501 for the treatment of Danon disease, less than three months after the hold was issued. According to the company, the FDA confirmed that issues outlined in the hold were satisfactorily addressed, allowing the trial to resume with a recalibrated dose of 3.8 x 10¹³ GC/kg in three patients, administered sequentially with a minimum four-week interval.1
How Will the Revised Dosing and Regimen Shape the Trial?
Rocket provided additional context on the dosing and immunomodulatory plan. In a press release, the company noted that the adjusted dose is aligned with the lower range of doses that were already administered and showed safety and efficacy in multiple biomarkers, echocardiographic and clinical endpoints from the Phase I portion of the trial.
The manufacturer added that it will collaborate with trial investigators to administer an immunomodulatory regimen that is more closely aligned with what patients received in the Phase I pediatric cohort.
Thus far, the adjusted dose has been administered six patients with Danon disease. Additional updates regarding the trial are expected to be released after data from the next three patients become available.
Trial Design and Endpoints
- The global, single-arm, multi-center pivotal trial is currently evaluating the efficacy and safety of RP-A501 in 12 patients with Danon disease.
- The trial started with pediatric safety run-in of two patients and has since enrolled a total of six individuals who received treatment at a dose of 6.7 x 10¹³ GC/kg.
- As indicated under the updated protocol that Rocket agreed upon with the FDA after the clinical hold was lifted, the next three patients will receive a lower dose of 3.8 x 10¹³ GC/kg, each treated at least four weeks apart, before enrolling the remaining participants to complete the trial.
- The primary endpoint of the trial is to evaluate the efficacy of RP-A501 via co-primary endpoint comprised of lysosome-associated membrane protein 2 isoform B (LAMP2B) myocardial tissue expression and left ventricular mass index.
- The key secondary endpoint is change in troponin.
- Additional secondary endpoints include natriuretic peptides, Kansas City Cardiomyopathy Questionnaire, New York Heart Association class, event free survival to two years, and treatment emergent adverse events (AEs).1,2
Patient Safety and Clinical Hold Background
The clinical hold was first announced in May after a patient experienced a serious AE that involved clinical complications related to a capillary leak syndrome. This eventually led to the patient’s death.3
