Neurogene Updates on NGN-401 Gene Therapy Trial for Rett Syndrome

NEW YORK, NY, USA I November 18, 2024 I Neurogene Inc. (Nasdaq: NGNE), a company dedicated to developing genetic medicines for rare neurological diseases, has provided an update on its Phase 1/2 open-label clinical trial of NGN-401 gene therapy for treating Rett syndrome.

On November 11, 2024, Neurogene reported a serious adverse event (SAE) in a participant who received NGN-401 at the higher dose level of 3E15 vg. The participant, who was dosed on November 5, exhibited symptoms of a systemic hyperinflammatory syndrome, a critical immune response witnessed with high doses of AAV. This condition, linked with abnormal cytokine release, can lead to hemophagocytic lymphohistiocytosis (HLH) and multisystem inflammatory syndrome. The participant remains in critical condition as the situation develops.

Rachel McMinn, Ph.D., Founder and CEO of Neurogene, expressed deep sympathy for the affected family and emphasized that the safety of trial participants is their primary concern as they strive to find solutions for Rett syndrome.

Neurogene has engaged with the FDA under the START program to ensure full transparency regarding the SAE. The FDA reviewed the safety data for NGN-401 and permitted the continuation of the Phase 1/2 trial at the lower dose of 1E15 vg. Neurogene has halted the use of the 3E15 vg dose and will not enroll additional participants at this dose level.

Thus far, no other treatment-related SAEs have been observed in the trial, which includes five participants who received the low dose and two who received the high dose of NGN-401. Treatment-related adverse events (AEs) in the low-dose group have been mild and manageable with steroids. Importantly, there have been no signs of MeCP2 overexpression toxicity or AEs related to the intracerebroventricular (ICV) procedure.

Due to the discontinuation of the high-dose cohort, Neurogene no longer expects to complete enrollment in the low-dose cohort by the fourth quarter of 2024. The trial protocol is being updated to reflect these changes.

Neurogene is committed to developing treatments for severe neurological diseases to enhance the lives of patients and their families. Their innovative strategies aim to overcome the challenges of conventional gene therapy for central nervous system disorders by optimizing delivery methods and product design for efficacy and safety. The company's proprietary EXACT™ transgene regulation platform technology enables therapeutic delivery while minimizing transgene toxicity. Neurogene has established a gene therapy manufacturing facility in Houston, Texas, which supports the production and clinical development of NGN-401.