Neurogene completes dosing in gene therapy trial for Rett syndrome

Neurogene announced the successful completion of dosing in the Embolden registrational trial of NGN-401, an investigational gene therapy designed to be a one-time treatment for Rett syndrome.

Embolden is a multi-center, single-arm, open-label, baseline-controlled registrational trial designed to evaluate the efficacy, safety and tolerability of a one-time dose of NGN-401 (1E15 vg) in females with Rett syndrome ages three and older. Neurogene elected to overenroll the trial and dose all eligible participants already in screening for a total of 25.

NGN-401 is an AAV9 gene therapy in development as a potential best-in-class treatment for Rett syndrome, a rare genetic neurological disorder that primarily affects girls and causes severe impairments in communication, movement and cognitive function.

The Embolden trial builds on positive interim data from the phase 1/2 trial of NGN-401, which demonstrated multidomain, durable gains with continued developmental milestone acquisitions. In November 2024, however, Neurogene halted the high-dose cohort of the phase 1/2 clinical trial after a patient experienced signs of a systemic hyperinflammatory syndrome — a life-threatening immune response that has been reported with systemic exposure to high doses of AAV. That patient later died, triggering an FDA review of the safety data for NGN-40. The agency allowed the company to proceed with the phase 1/2 trial using the low-dose cohort, 1E15 vg dose.

As of June 7, 2026, NGN-401 at the 1E15 vg dose continues to be generally well-tolerated. There were no cases of hemophagocytic lymphohistiocytosis at this dose level in the phase 1/2 trial or the Embolden trial.

The primary analysis to support the planned BLA submission is expected to occur after the first 24 participants have completed 12 months of follow-up, with topline data expected in the second half of 2027.