The FDA Lifts Clinical Hold On Rocket Pharmaceuticals' Pivotal Phase 2 Trial Of RP-A501 For Danon Disease
Benzinga Newsdesk 1 year ago
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In its correspondence, the FDA confirmed that Rocket satisfactorily addressed issues outlined in the clinical hold. The FDA authorized the pivotal study to resume first with a recalibrated dose of 3.8 x 10¹³ GC/kg of
In its correspondence, the FDA confirmed that Rocket satisfactorily addressed issues outlined in the clinical hold. The FDA authorized the pivotal study to resume first with a recalibrated dose of 3.8 x 10¹³ GC/kg of RP-A501 in three patients, treated sequentially with a minimum four-week interval between each treatment. This adjusted dose aligns with the lower range of administered doses that were associated with efficacy across multiple biomarkers, echocardiographic and clinical endpoints in the Phase 1 study, and has been determined as most likely to confer the safety and efficacy identified in the low-dose Phase 1 cohorts. In addition, Rocket will collaborate with investigators to implement an immunomodulatory regimen more closely reflecting that administered in the Phase 1 pediatric cohort. The revised regimen discontinues prophylactic use of a C3 complement inhibitor, while maintaining sirolimus, rituximab, and steroids. Additionally, the protocol will specify a lower threshold for administering a C5 inhibitor (eculizumab) in response to impending complement activation.
To date, six patients with Danon disease have been treated in the Phase 2 study with RP-A501. Further updates about the Phase 2 study can be expected following review of data from the next three patients.
RP-A501 Phase 2 Pivotal Trial Overview
The global, single-arm, multi-center 12-patient Phase 2 pivotal trial evaluates the efficacy and safety of RP-A501 for the treatment of Danon disease. The trial began with a pediatric safety run-in (n=2) and treated a total of six patients at a dose level of 6.7 x 1013 GC/kg. Per alignment with the FDA upon lifting of the clinical hold, three additional patients are expected to be treated at a dose level of 3.8 x 1013 GC/kg with a minimum four-week interval between dosing, followed by additional patients to complete the trial.
- To support accelerated approval, the study assesses the efficacy of RP-A501 as measured by the biomarker-based co-primary endpoint consisting of improvements in LAMP2 protein expression, and reductions in left ventricular mass.
- 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 24 months and treatment emergent safety events. These endpoints could support full approval with longer-term follow-up.
- A global natural history study is running concurrently with the Phase 2 pivotal trial.
- All patients enrolled in the trial are required to have a three-months observational pre-treatment run-in to enable an assessment of troponin (and other biomarker) trajectories to optimally assess this key secondary endpoint.