Neurogene completes FDA discussion on Embolden trial, announces NGN-401 data

Neurogene (NGNE) announced the company has completed discussions with the FDA on its Embolden registrational trial protocol and plans to initiate dosing in the fourth quarter of 2025. In response to strong interest from the Rett syndrome community, the trial is expected to enroll across 13 sites. Neurogene also announced new preclinical data from nonhuman primates demonstrating that intracerebroventricular delivery of NGN-401 achieves superior AAV biodistribution across brain regions relevant to Rett syndrome, compared to intrathecal lumbar delivery. These findings are consistent with preclinical data generated by other independent laboratories, reinforcing a growing body of evidence that supports ICV delivery for achieving greater expression in the brain. The head-to-head NHP study compared ICV and IT-L administration of NGN-401 at a dose that approximates the human dose being evaluated in the NGN-401 Phase 1/2 and Embolden clinical trials alongside a dose approximately four times higher than the clinically relevant dose administered via IT-L. Key results presented at the European Society of Gene & Cell Therapy Annual Congress in Seville, Spain, included: ICV administration of NGN-401 showed greater expression of the full-length therapeutic MECP2 transgene mRNA in key brain regions underlying Rett syndrome pathophysiology when compared to the same IT-L administered dose; more similar levels of RNA expression were observed in the lumbar spinal cord. Higher RNA expression in key areas of the brain was also observed when ICV was compared to the approximately four times higher dose IT-L cohort. Comparable peripheral exposure of vector genome biodistribution was observed in peripheral organs, including the liver, between equivalent ICV and IT-L doses, consistent with clinical data from intra-CSF administered products.