Acute systemic infection caused the patient to develop fatal capillary leak syndrome, highlighting the unpredictability of gene therapies and potentially challenging investment in the space, analysts say.
A patient has died in Rocket Pharmaceuticals’ pivotal Phase II trial for its investigational gene therapy RP-A501, which the biotech is developing for Danon disease.
The patient in question developed complications related to capillary leak syndrome, characterized by fluid leaking out of blood vessels and into surrounding tissues, resulting in a drop in blood pressure. The complication was unexpected and serious, Rocket said in its release on Tuesday, and prompted the company to voluntarily suspend dosing in the trial. The FDA placed a formal clinical hold on the trial on Friday.
The patient has since died. “Rocket is deeply saddened to report that this patient has since passed away after an acute systemic infection,” the company stated in its news release.
In a note to investors on Tuesday, analysts at Jefferies wrote that the mortality “hurts the benefit/risk profile of the Danon program,” while also strengthening the growing notion that serious toxicities “are unpredictable with gene therapies, making it challenging to invest in gene therapies broadly.” Jefferies added the development “seems fresh” and expects that the hold could take “weeks/months to resolve.”
BMO Capital Markets, meanwhile, had a more optimistic angle. “Despite Danon patient death, however, we still believe that RP-A501 benefit/risk is justified, given that Danon patients die” by around 20 years of age, the analysts wrote in a Tuesday note.
Rocket is comprehensively reviewing the incident to identify the cause, “with the current focus being on the recent introduction of a novel immune suppression agent to the pre-treatment regimen.” This medication, which according to Rocket is specific to its Danon program, was meant to suppress the activation of the complement system in preparation for the induction of the gene therapy.
The biotech is working with the FDA, an independent data monitoring board and the study’s investigators to ensure the safety of all enrolled patients, “while resuming the trial as expeditiously as possible,” it wrote on Tuesday.
As per the Jefferies note, the patient death and the clinical hold will put some pressure on Rocket’s finances. “Cash burn needs to be monitored,” the analysts wrote, estimating that Rocket spends anywhere from $40 million to $50 million per quarter. In its Tuesday release, Rocket noted that as of the end of Q1, it had $318.2 million in cash, cash equivalents and investments, giving it a runway into 2027.
Both BMO and Jefferies analysts agreed that Tuesday’s patient death will have broader implications for the gene therapy space, which in recent months has suffered several safety setbacks. In March, for instance, Sarepta Therapeutics reported that a patient treated with its Duchenne muscular dystrophy gene therapy Elevidys died. There were also two mortalities in November 2024: one in Neurogene’s Phase I/II Rett syndrome study and another for Beam Therapeutics’ base editor BEAM-101 for sickle cell disease.
The gene therapy space also lost a vocal advocate with the recent exit of the FDA’s Peter Marks, former director of the agency’s Center for Biologics Evaluation and Research.
