Rocket Pharmaceuticals, a fully integrated, late-stage biotechnology company advancing a sustainable pipeline of genetic therapies for rare disorders with high unmet need, announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the Company’s pivotal Phase 2 trial of RP-A501 for the treatment of Danon disease. 

The hold was lifted in under three months, underscoring the efficiency of the FDA’s review process and Rocket’s commitment to expeditiously optimize safety and resume the trial. 

In its correspondence, the FDA confirmed that Rocket satisfactorily addressed the issues outlined in the clinical hold. The agency authorized the pivotal study to resume with a recalibrated dose of 3.8 x 10 1 3 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 demonstrated efficacy across multiple biomarkers, echocardiographic measures, 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. 

Rocket will also 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, and specifies 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 are expected following the review of data from the next three patients. 

The pivotal Phase 2 trial is a global, single-arm, multi-center study enrolling 12 patients to evaluate the efficacy and safety of RP-A501 for the treatment of Danon disease. The trial began with a pediatric safety run-in of two patients and has treated a total of six patients at a dose level of 6.7 x 10 13 GC/kg. Following the FDA’s guidance upon lifting of the clinical hold, three additional patients will now be treated at a dose level of 3.8 x 10 1 3 GC/kg with a minimum four-week interval between dosing, after which additional patients will be enrolled to complete the study.