Neurogene Reports Positive Safety Data for NGN-401 in Rett Syndrome Trial

Neurogene Inc., a clinical-stage company focused on genetic medicines for rare neurological disorders, has announced promising initial safety and tolerability data from its ongoing Phase 1/2 gene therapy clinical trial for Rett syndrome. The therapy, NGN-401, has shown to be generally well-tolerated in the first three patients dosed, with follow-up periods of around nine, six, and three months. This data was unveiled at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting.

Rachel McMinn, Ph.D., the Founder and CEO of Neurogene, highlighted the innovative design of NGN-401, which integrates their EXACTTM transgene regulation technology. This technology aims to achieve therapeutic levels of protein expression in critical brain and nervous system regions, addressing limitations seen in conventional gene therapy for Rett syndrome. The initial data suggests favorable tolerability in the first three pediatric patients, with no signs of overexpression toxicity, even in a patient with a mild variant expected to result in residual MeCP2 expression.

The Phase 1/2 open-label trial is assessing the safety, tolerability, and early efficacy of two dose levels of NGN-401, administered through a one-time intracerebroventricular (ICV) infusion. Currently, the trial is enrolling female patients aged 4-10 years with classic Rett Syndrome and a Clinical Global Impression-Severity (CGI-S) score of 4-6, into both low-dose Cohort 1 and high-dose Cohort 2.

The demographic details of the first three patients in Cohort 1 (1E15 vector genomes) are as follows:
- Patient 1: Age 7, Asian, mild MECP2 mutation, ~9 months post-administration.
- Patient 2: Age 4, White, severe MECP2 mutation, ~6 months post-administration.
- Patient 3: Age 6, White, severe MECP2 mutation, ~3 months post-administration.

NGN-401 has been well-tolerated across all three patients, with all treatment-related adverse events (AEs) being mild (Grade 1) and transient. Most of these AEs are recognized potential risks associated with adeno-associated virus (AAV) therapies, such as asymptomatic changes in laboratory values. Importantly, there have been no indications of MeCP2 overexpression toxicity, nor any treatment-emergent or ICV procedure-related serious adverse events (SAEs).

Dr. Bernhard Suter, Medical Director of the Blue Bird Circle Rett Center at Texas Children’s Hospital and principal investigator in the NGN-401 trial, emphasized the high unmet need for new treatments for Rett syndrome. He expressed optimism about the potential of gene therapy to address the underlying cause with a one-time treatment and highlighted the significance of the interim safety data from the NGN-401 trial. Dr. Suter is looking forward to continuing the trial to further evaluate the safety and efficacy of NGN-401.

Neurogene plans to release interim clinical data, including efficacy outcomes, from Cohort 1 in the fourth quarter of 2024, and additional interim data from Cohort 2 in the second half of 2025.

The mission of Neurogene is to bring transformative treatments for severe neurological diseases, utilizing advanced approaches to overcome the limitations of traditional gene therapy. This includes optimizing delivery approaches to target tissues, designing products for maximum efficacy and safety, and leveraging their proprietary EXACT transgene regulation technology to achieve therapeutic levels while minimizing toxicity. Neurogene has established a state-of-the-art manufacturing facility in Houston, Texas, to support its clinical development activities, including the production of NGN-401 for its pivotal trials.