Neurogene Details New Safety Measures After Young Patient’s Death in Rett Syndrome AAV Gene Therapy Trial

A young patient participating in Neurogene's Phase I/II trial of NGN-401 for Rett syndrome died following complications from hemophagocytic lymphohistiocytosis (HLH), a rare hyperinflammatory syndrome linked to high-dose AAV gene therapy15.

NGN-401 utilizes an AAV vector to deliver functional copies of the MECP2 gene, which is commonly mutated in Rett syndrome1.

Following the patient's death—which occurred about two weeks after dosing at the 3E15 vg level—Neurogene discontinued the trial's high-dose (3E15 vg) arm and will now only use a lower 1E15 vg dose with FDA approval15.

HLH is a known but uncommon risk of AAV-based gene therapies, marked by immune dysregulation, cytokine storm, and multi-organ failure1.

Neurogene has announced new, evidence-based monitoring and treatment protocols intended to reverse rare hyperinflammatory responses associated with high-dose AAV exposure2.

The revised trial design and safety measures were presented at the American Society of Gene & Cell Therapy (ASGCT) conference in May 20251.

Neurogene's stock suffered a substantial decrease following news of the adverse event and patient death5.

Sources:

1. https://www.fiercebiotech.com/biotech/neurogene-details-severe-aav-reaction-led-young-patients-death-rett-syndrome-gene-therapy

2. https://ir.neurogene.com/news-releases/news-release-details/neurogene-announces-evidence-based-monitoring-and-treatment

5. https://www.clinicaltrialsarena.com/news/patient-dies-in-neurogenes-phase-i-ii-rett-syndrome-trial/