Neurogene reports patient death in Rett syndrome gene therapy trial

Neurogene has reported the death of a participant in its phase 1/2 clinical trial for Rett syndrome due to complications from a rare hyperinflammatory syndrome.

The patient, who received a 3E15 vg dose of NGN-401 on November 5, experienced severe systemic exposure to high doses of adeno-associated virus (AAV), resulting in a fatal outcome. NGN-401 is a gene therapy candidate designed to address the genetic basis of Rett syndrome, a rare neurological condition.

Following the incident, the FDA has permitted the trial to continue using a lower 1E15 vg dose for both pediatric and adolescent/adult cohorts. Neurogene has confirmed that this reduced dose will also be incorporated into the design of its future registrational trials. The decision reflects a cautious approach to patient safety while advancing therapy development.

This development raises broader questions about the safety and regulation of experimental treatments for rare diseases. Neurogene has not disclosed further details about the impact on its timeline or any additional changes to its clinical program.