Rocket Pharmaceuticals, Inc. (NASDAQ:RCKT), a fully integrated, commercial-stage biotechnology company advancing genetic medicines for rare and life-threatening diseases, focused on inherited cardiovascular disorders, today announced alignment with the U.S. Food and Drug Administration (FDA) on continued enrollment and dosing and key elements of the global pivotal Phase 2 trial of RP-A501 for the treatment of Danon disease, including the recalibrated dose, 12-patient pivotal population and established 12-month co-primary endpoints.

The clinical data reviewed by FDA included results from the first three patients treated under the modified protocol. All three completed at least four weeks of follow-up and had been discharged following protocol-specified observation. No clinical or laboratory evidence of thrombotic microangiopathy or capillary leak syndrome had been observed. Following its review of the available safety data, the FDA confirmed continued enrollment and dosing under the modified protocol at the recalibrated dose.

The FDA also confirmed that the pivotal study population will include 12 male patients treated with RP-A501 at the recalibrated dose of 3.8 × 10¹³ genome copies per kilogram (GC/kg) using commercial-grade product. Importantly, the first three patients treated at the recalibrated dose under the modified protocol count toward the 12-patient pivotal population, leaving nine additional patients to be enrolled and treated. Rocket expects to complete dosing of the remaining patients by mid-2027.

The primary assessment will occur at 12 months using the previously established co-primary endpoints of myocardial LAMP2 protein expression and a 10% reduction from baseline in left ventricular mass index. These endpoints are intended to support a potential accelerated approval pathway.

"FDA’s confirmation of the pivotal efficacy framework marks an important milestone for RP-A501 and the Danon disease community," said Gaurav Shah, M.D., Chief Executive Officer of Rocket Pharmaceuticals. "With the first three patients counting toward the 12-patient pivotal population and the established co-primary endpoints preserved, we now have a clear and actionable path to complete the pivotal study. The initial clinical experience at the recalibrated dose and supportive product-bridging data further reinforce the path forward."

The modified protocol incorporates a recalibrated RP-A501 dose and an optimized immunomodulatory regimen comprised of rituximab, sirolimus and corticosteroids, together with enhanced eligibility criteria, safety monitoring and risk-mitigation measures. The recalibrated dose was selected based on analytical characterization of the Phase 2 commercial-grade product, including its full-particle content, and is supported by nonclinical bridging data.

Nonclinical bridging data further support the pharmacologic activity of the recalibrated dose. In a Danon disease mouse model, administration of Phase 2 material at 3.8 × 10¹³ GC/kg resulted in cardiac LAMP2B protein expression comparable to that observed at a higher dose and demonstrated comparable vector biodistribution.