The U.S. Food and Drug Administration (FDA) has placed a clinical hold on Rocket Pharmaceuticals’ pivotal gene therapy trial following the death of a patient treated with RP-A501 for Danon disease. The hold has triggered a significant shift in Rocket’s trial and financial timelines, as the company seeks to assess safety protocols and extend its cash runway into 2027.
RP-A501 is an investigational AAV9-based gene therapy designed to treat Danon disease—a rare, life-threatening genetic condition that weakens the heart muscle—by delivering the LAMP2B transgene directly to cardiac cells. The therapy is currently under evaluation in a Phase 2 trial involving 12 patients at Rocket’s New Jersey facility.
The FDA intervened after a patient developed capillary leak syndrome approximately one week after receiving the gene therapy, later succumbing to complications from an infection. Rocket had previously adjusted its pre-treatment protocol to include a C3 inhibitor, aiming to mitigate complement activation and thrombotic microangiopathy (TMA)—a serious vascular condition observed in earlier participants. While TMA was not detected in the two patients who received the C3 inhibitor, both developed capillary leak syndrome, and one of them died.
CEO Gaurav Shah emphasized that the biotech acted swiftly after detecting early signs of adverse reactions, halting further dosing and notifying the FDA. While the exact cause is under investigation, the correlation between the C3 inhibitor and capillary leak syndrome raises new safety questions. Shah stated that Rocket is committed to refining the therapy and resuming the trial once it’s deemed safe.
Despite the setback, Rocket maintains that RP-A501 holds promise. The company is revising its data reporting schedule to mid-2026 and has extended its financial runway by prioritizing AAV gene therapy efforts. As of March, Rocket held $318.2 million in cash, now redirected to focus on its lead programs.
Importantly, the FDA’s clinical hold does not impact Rocket’s other pipeline programs, including those targeting PKP2 and BAG3. However, investor confidence took a hit, with Rocket’s stock plunging 63% in premarket trading to $2.29.
Rocket has not provided a timeline for when the FDA hold may be lifted but remains optimistic about collaborating with regulators to resume the trial under enhanced safety measures.
