US experts in gene therapy for Duchenne muscular dystrophy (DMD) have investigated the causes of two deaths that occurred in 2025 and were attributed to the administration of a single dose of dilandistrogene moxeparvovec (Elevidys®). They propose the following preventive measures:
- the two patients concerned were aged 15 and 16 respectively and had no risk factors other than their DMD,
- the first symptoms appeared four weeks after the initial infusion and manifested as elevated transaminases, followed by full-blown hepatocellular failure leading to death,
- The authors emphasise the warning and adverse nature of the sharp rise in bilirubin levels, even as liver enzyme levels were tending to normalise;
- pre-injection liver function tests will now need to be more comprehensive and more frequent in order to identify patients at risk;
- However, there is no consensus on whether or not it is necessary to prevent this type of adverse event by using a high-dose immunosuppressive regimen (such as sirolimus) prior to gene therapy.
