Neurogene’s Rett Syndrome Trial Halted After Patient Death Linked to High-Dose Gene Therapy

Patient Death:
A patient participating in Neurogene's Phase I/II Rett syndrome trial has died due to complications from a rare hyperinflammatory syndrome associated with high doses of adeno-associated virus (AAV) based therapies[1][3][5].

High-Dose Arm Halted:
The company has paused further use of the 3E15 vg dose and does not plan to enroll any further participants on this dose arm of the trial[1][3].

Trial Background:
The trial (NCT05898620) aims to examine NGN-401, a gene therapy for female pediatric patients with Rett syndrome, using Neurogene’s EXACT transgene regulation technology to deliver the full-length human MECP2 gene[1].

Previous Outcomes:
The first four participants showed consistent, concordant improvements across key Rett syndrome scales, achieving the score of “much improved” on the Clinical Global Impression-Improvement (CGI-I) scale[1].

Future Plans:
Neurogene will continue to engage with the FDA on planning for a future registrational clinical trial and anticipates providing an update on the trial design in the first half of 2025[1].

Stock Impact:
The company’s stock price has significantly dropped since the initial announcement of the adverse event, from $71.53 to $15.59 per share[1].