A pivotal moment for Rocket Pharmaceuticals and patients with Danon disease has just taken a devastating turn. Gaurav Shah, M.D., CEO of Rocket, is now under close scrutiny as the company faces a halt on its most critical gene therapy study.

According to Fierce Biotech, the U.S. Food and Drug Administration (FDA) has imposed a clinical hold on Rocket Pharmaceuticals’ phase 2 trial of its gene therapy, RP-A501, after a patient died following treatment complications. This pause comes as Rocket was preparing to release pivotal data by mid-2026 but now must regroup and address safety concerns before moving forward.

Rocket’s plan was to use its AAV9-mediated gene therapy to restore heart function in patients with Danon disease, a rare and deadly disorder causing progressive heart muscle weakness. The phase 2 trial, which aimed to support accelerated FDA approval, was dosing just 12 patients in hopes of a breakthrough.

Patient complications raise alarms

The clinical hold was triggered after a trial participant developed capillary leak syndrome—a rare but serious complication—within one week of infusion. According to Shah, the patient’s condition initially appeared to stabilize, leading to cautious optimism among the medical team. However, the patient’s health rapidly declined after a sudden systemic infection, ultimately resulting in death.

Rocket responded promptly by notifying the FDA and ceasing all further dosing. The FDA’s swift action to institute a clinical hold before the patient died signals the agency’s heightened vigilance around new gene therapies, especially after a series of high-profile safety concerns within the biotech sector.

Shah detailed the sequence of events on a call with investors, explaining both the medical complications and the company’s efforts to intervene. He admitted the patient’s initial signs of recovery gave hope, but the turn for the worse over the weekend left the company reeling and the trial in limbo.

Changes to trial protocol spark debate

Rocket’s investigation identified a key change in its pretreatment regimen as a possible trigger for the adverse event. The company had recently added a C3 inhibitor—an immunomodulatory agent—to prevent a life-threatening blood vessel condition called thrombotic microangiopathy (TMA). While this addition aimed to improve safety, it appears to have introduced new risks.

Patients who received the original regimen without the C3 inhibitor avoided TMA and are reportedly doing well, both in terms of safety and potential efficacy. However, the two patients who received the new protocol with the C3 inhibitor both developed capillary leak syndrome, and one died. After learning from the first patient’s case, Rocket intervened early with the second, preventing a repeat of the same complications.

Shah pointed out that only those receiving the C3 inhibitor experienced a capillary leak, leading Rocket to suspect the drug as the possible culprit. He maintained that the company is “confident there is a path forward” and is actively collaborating with the FDA to resolve the clinical hold.

Investor reaction and market implications

News of the FDA hold, and patient death immediately rocked investor confidence. Shares of Rocket Pharmaceuticals plummeted 63% in premarket trading to $2.29. Analysts at William Blair acknowledged investor hesitancy surrounding the program’s safety and the timeline for resolving the hold but suggested there remains a way forward for Rocket if safety protocols are improved.

Despite the setback, Rocket’s other major programs—including those for PKP2 and BAG3—remain unaffected. The company finished March with $318.2 million and announced plans to prioritize investments in its AAV gene therapy platform while conducting an internal review to maximize the value of its pipeline. Leadership aims to extend its cash runway into 2027, adjusting strategy to weather the current storm.

William Blair analysts commented, “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.”

Why This Story Matters

This story has profound implications for the scientific and medical communities, particularly in the development of gene therapies and the safety protocols they follow. It sheds light on the complexities and risks tied to experimental treatments, even as they offer hope to those with rare conditions.

For the public, the incident underscores the value of transparency in biotechnology and the importance of strong regulatory oversight. Communities benefit when companies and agencies prioritize patient safety over speed. Finally, the tragedy invites a deep reflection on how far science is willing to go to save lives and what caution must accompany ambition in the pursuit of medical innovation.

Conclusion

Rocket’s RP-A501 gene therapy trial for Danon disease was halted after a patient died from complications linked to a new C3 inhibitor added to reduce TMA risk. The FDA has imposed a clinical hold while Rocket reviews its approach and talks with regulators about resuming the study. Other Rocket programs, including RP-A601, are unaffected since they use different methods.