Neurogene's Rett Syndrome Trial Halted After Patient Death

• A patient in Neurogene's Phase I/II trial for Rett syndrome gene therapy, NGN-401, died due to complications from a hyperinflammatory syndrome linked to AAV-based therapies.
• The patient received a 3E15 vg dose of NGN-401 on November 5th, and the trial has been paused for the 3E15 vg dose, with no further participants to be enrolled in that arm.
• Neurogene's stock price has significantly decreased following the adverse event and subsequent death, impacting the company's market value.
• The company plans to engage with the FDA to plan a future registrational clinical trial and expects to provide an update on the trial design in the first half of 2025.

A patient participating in Neurogene's Phase I/II clinical trial (NCT05898620) for Rett syndrome has died due to complications arising from a rare hyperinflammatory syndrome associated with adeno-associated virus (AAV) based therapies. The trial was evaluating NGN-401, a gene therapy intended as a one-time treatment for Rett syndrome.

The patient, who was administered a 3E15 vg dose of NGN-401 on November 5th, experienced critical complications leading to death on November 18th. The news of the adverse event initially caused Neurogene's stock to plummet by 34% in premarket value, and the stock has continued to decline since the patient's death, reaching $15.59 per share, a significant drop from its previous high of $71.53.

Trial Details and NGN-401

NGN-401 is an investigational AAV9 gene therapy that utilizes Neurogene’s EXACT transgene regulation technology to deliver the full-length human MECP2 gene. The open-label trial aims to assess the safety and efficacy of NGN-401 in female pediatric patients with Rett syndrome, a genetic disorder typically manifesting between 6 and 18 months of age, predominantly affecting girls and leading to developmental and health challenges.

Impact on Trial and Future Plans

Following the initial adverse event, Neurogene paused further use of the 3E15 vg dose. The company has confirmed that it will not enroll any additional participants in the 3E15 vg dose arm of the trial. Despite this setback, Neurogene reported that the first four participants in the trial showed consistent improvements across key Rett syndrome scales, achieving a score of "much improved" on the Clinical Global Impression-Improvement (CGI-I) scale.

Company Statement and Next Steps

Neurogene founder Rachel McMinn stated on November 18th that the company has observed girls gaining complex skills rarely seen in this population, including skills that were previously lost during the regression phase of the disease. Neurogene plans to continue discussions with the FDA regarding the design of a future registrational clinical trial and anticipates providing an update on the trial design in the first half of 2025.