The FDA has slapped a clinical hold on Rocket Pharmaceuticals’ pivotal gene therapy trial in response to a death. Rocket, which was aiming to report data in mid-2026, dropped its targeted trial completion date and outlined actions to extend its cash runway after suffering the setback.
New Jersey-based Rocket is testing its gene therapy RP-A501 in patients with Danon disease, a condition associated with weakening of the heart muscle. The biotech’s pivotal phase 2 trial is assessing the AAV9 gene therapy in 12 patients to support accelerated approval. RP-A501 is designed to fully restore cardiac function by delivering the LAMP2B transgene to heart cells.
Rocket stopped dosing in the phase 2 study and notified the FDA after a patient developed complications linked to capillary leak syndrome. Gaurav Shah, M.D., CEO at Rocket, discussed the timeline of events on a call with investors Tuesday, explaining that the company saw signs of capillary leak around one week after infusion.
“There were other medical complications and procedural complications in the week or so afterwards, and actually the patient was at that time stable and doing potentially well enough that we were cautiously optimistic over recovery and the capillary leak was improving,” Shah said. “Unfortunately, over the weekend ... he developed an acute systemic infection that accelerated his demise.”
The FDA imposed the clinical hold Friday, before the patient died, to enable evaluation of the causes of the adverse event. Rocket has identified the addition of a C3 inhibitor to the pretreatment regimen as a potential cause of the capillary leak syndrome. The biotech added the immunomodulatory agent to the regimen to counter complement activation by the AAV and prevent thrombotic microangiopathy (TMA).
Rocket saw complement activation and TMA, a potentially life-threatening blood vessel condition, in patients who received the original pretreatment regimen. Those patients “are actually now doing well from a safety and potentially even an efficacy viewpoint,” Shah said, but Rocket changed pretreatment in the belief “the timing was right to try to eradicate the risk of TMA.”
The biotech didn’t see TMA in the two patients who received the C3 inhibitor but both participants had capillary leak syndrome. The first patient died. Shah said Rocket learnt from the first case and intervened “so that we didn't see the same events happening in the second patient.” Rocket only saw capillary leak in people who received the C3 inhibitor, leading it to finger the drug as a possible cause of the syndrome.
Shah said Rocket is confident there is a path forward and is committed to advancing RP-A501. The biotech is in talks with the FDA but is yet to provide a timeline for resolving the hold. Patients are waiting to be treated but Rocket cannot resume dosing until it receives the green light from the FDA. The agency has, if anything, “been more responsive and more collaborative and faster” than in the past, Shah said.
Rocket, which ended March with $318.2 million, is “prioritizing investments into its AAV platform while conducting an internal strategic review to optimize value for the rest of the pipeline,” Shah said. The changes will extend the biotech’s cash runway into 2027, compared to late 2026 under the previous plan.
Rocket’s PKP2 and BAG3 programs are on track and unaffected by the clinical hold, Shah said.
Shares in Rocket fell 63% to $2.29 in premarket trading.
Analysts at William Blair said in a note to clients that: “With the stock down […] following the company’s announcement, we believe investors are hesitant about the program’s safety and time to clinical hold resolution. However, we continue to believe there is a path forward for the program once a modified safety plan is implemented.”
The firm added that it was not seeing a read-through to Rocket’s other clinical cardiovascular program, namely RP-A601 for the treatment of Plakophilin-2 associated arrhythmogenic cardiomyopathy, “given that it utilizes a different AAV vector (AAVrh74) and does not include the C3 inhibitor in its immunosuppression protocol.”