The U.S. Food and Drug Administration has placed a clinical hold on Rocket Pharmaceuticals' pivotal Phase II gene therapy trial after a patient death linked to serious complications from the experimental treatment. The FDA action, announced Tuesday, follows the development of capillary leak syndrome in a patient receiving RP-A501, an investigational gene therapy for Danon disease.
Patient Death Triggers Safety Review
The patient developed capillary leak syndrome, a serious condition characterized by fluid and proteins leaking from tiny blood vessels into surrounding tissues, causing swelling and dangerously low blood pressure. According to Rocket, the complication was "unexpected and serious," prompting the company to voluntarily suspend dosing in the trial before the FDA formalized the clinical hold on Friday.
"Rocket is deeply saddened to report that this patient has since passed away after an acute systemic infection," the company stated in its Tuesday release. The New Jersey-based biotech is now conducting a comprehensive review of the incident to identify the underlying cause.
Focus on Novel Immune Suppression Agent
Rocket's investigation is currently focusing on "the recent introduction of a novel immune suppression agent to the pre-treatment regimen." This medication, which the company notes is specific to its Danon program, was designed to suppress activation of the complement system in preparation for gene therapy induction.
The company is working with the FDA, an independent data monitoring board, and study investigators to ensure patient safety while seeking to resume the trial "as expeditiously as possible." However, Rocket cannot provide a timeline for completion until the clinical hold is lifted.
Market Impact and Financial Implications
The safety setback sent Rocket's shares tumbling 63% to $2.30 in premarket trading Tuesday, down from Friday's close of $6.27. Analysts at Jefferies noted that the mortality "hurts the benefit/risk profile of the Danon program" while strengthening concerns that serious toxicities "are unpredictable with gene therapies, making it challenging to invest in gene therapies broadly."
The clinical hold is expected to impact Rocket's financial position, with Jefferies analysts estimating the company spends $40 million to $50 million per quarter. As of the end of Q1, Rocket reported $318.2 million in cash, cash equivalents and investments, providing a runway into 2027.
Broader Gene Therapy Safety Concerns
The incident adds to mounting safety concerns in the gene therapy sector. BMO Capital Markets analysts acknowledged that while the patient death is concerning, they "still believe that RP-A501 benefit/risk is justified, given that Danon patients die" by around 20 years of age.
Recent months have seen several gene therapy safety setbacks across the industry. In March, Sarepta Therapeutics reported a patient death following treatment with its Duchenne muscular dystrophy gene therapy Elevidys. November 2024 brought two additional mortalities: one in Neurogene's Phase I/II Rett syndrome study and another involving Beam Therapeutics' base editor BEAM-101 for sickle cell disease.
About Danon Disease and RP-A501
Danon disease is a rare genetic disorder that causes progressive heart muscle damage and muscle weakness. RP-A501 represents Rocket's investigational gene therapy approach to treating this devastating condition, which typically proves fatal by the patient's twenties.
Jefferies analysts expect the clinical hold could take "weeks/months to resolve" as regulators and the company work through the safety investigation. The outcome will likely have implications not only for Rocket's Danon program but for broader confidence in gene therapy development across the industry.
