Neurogene Doses First High-Dose Patient in NGN-401 Rett Syndrome Trial

Neurogene Inc. (Nasdaq: NGNE), a clinical-stage company focused on genetic medicines for rare neurological disorders, announced progress in its Phase 1/2 trial of NGN-401 for treating female pediatric patients with Rett syndrome. The trial's second cohort has begun receiving high-dose NGN-401, and initial results indicate that this dosage is well-tolerated. Additionally, interim safety data from the first three patients in the low-dose cohort were presented at the IRSF ASCEND 2024 Rett Syndrome National Summit, showing no new treatment-related adverse events.

Rachel McMinn, Ph.D., Founder and CEO of Neurogene, emphasized the significance of reaching the milestone for high-dose cohort dosing and reported that early safety profiles for high-dose NGN-401 appear favorable. McMinn explained that NGN-401 is designed to deliver consistent and controlled full-length MECP2 expression to critical areas of the brain and nervous system. She indicated that the company plans to release interim efficacy data for the low-dose cohort by the fourth quarter of 2024 and is collaborating with the FDA’s START Pilot Program to expedite NGN-401’s development.

During the summit, Bernhard Suter, M.D., Medical Director of the Blue Bird Circle Rett Center at Texas Children’s Hospital and principal investigator of the NGN-401 trial, provided updated safety data for the low-dose cohort. The findings revealed that NGN-401 continues to demonstrate a favorable safety profile with no new treatment-related adverse events reported since the previous update at the ASGCT Annual Meeting. All treatment-related adverse events were mild, transient, or resolving, with most being known risks associated with AAV-based therapies. Notably, there were no indications of MeCP2 overexpression toxicity, even in a patient with a mild genetic variant. Additionally, there were no serious adverse events related to the treatment or intracerebroventricular (ICV) procedures.

NGN-401 is an investigational AAV9 gene therapy developed as a one-time treatment for Rett syndrome. It delivers the full-length human MECP2 gene regulated by Neurogene’s EXACT™ technology. This approach aims to achieve targeted MECP2 transgene expression levels without the overexpression-related toxic effects commonly seen in conventional gene therapies. The FDA has selected NGN-401 for its START Pilot Program, and it has received multiple designations, including orphan drug status, Fast Track status, and rare pediatric status. The European Medicines Agency and the UK's Medicines and Healthcare products Regulatory Agency have also granted orphan designation and advanced therapy medicinal product designation, respectively.

Neurogene’s mission is to develop treatments for rare neurological diseases, focusing on overcoming the limitations of traditional gene therapies in central nervous system disorders. Their EXACT platform technology aims to deliver therapeutic levels of transgenes while minimizing toxicity. Neurogene has established a gene therapy manufacturing facility in Houston, Texas, where CGMP production of NGN-401 occurs, supporting pivotal clinical development activities.

In summary, Neurogene Inc. has made significant strides in its gene therapy trial for Rett syndrome, with high-dose NGN-401 showing favorable initial safety results and low-dose NGN-401 continuing to maintain a good safety profile. The company remains on track to share interim efficacy data later in the year and is working closely with regulatory bodies to advance the development of this promising treatment.