Neurogene's NGN-401 Gene Therapy for Rett Syndrome Chosen for FDA START Pilot Program

Neurogene Inc., a pioneering clinical-stage company specializing in genetic medicines for rare neurological disorders, has announced a significant milestone for its NGN-401 gene therapy aimed at treating Rett syndrome. The U.S. Food and Drug Administration (FDA) has included NGN-401 in its Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program. This selection underscores the therapy's potential clinical benefits and readiness for further development.

The START Program, initiated by the FDA, aims to accelerate the development of treatments for rare diseases by providing selected sponsors with enhanced communication opportunities. These interactions include frequent advice and regular discussions that address specific development issues, such as clinical study design and patient population selection. Neurogene's CEO, Rachel McMinn, expressed gratitude for the FDA's commitment to accelerating NGN-401's development, highlighting the therapy's potential to benefit patients and families affected by Rett syndrome.

NGN-401 is currently under evaluation in a Phase 1/2 clinical trial, which investigates the safety, tolerability, and preliminary efficacy of a one-time intracerebroventricular (ICV) administration in pediatric female patients with Rett syndrome. Early safety data from the first three patients dosed have been favorable, and Neurogene anticipates reporting interim efficacy data in the fourth quarter of 2024.

The FDA's START Program aims to expedite the development of promising drug and biological product candidates by facilitating more frequent and rapid interactions. Applicants to the program must present comprehensive clinical, CMC (chemistry, manufacturing, and controls), and non-clinical development plans. The FDA evaluates these applications based on several factors, including the potential clinical benefits of the product, alignment of development plans, and the ability to progress towards a marketing application. Selected sponsors are expected to receive ongoing advice from FDA staff to ensure the generation of high-quality and reliable data supporting future market applications.

NGN-401 stands out as an investigational AAV9 gene therapy designed as a one-time treatment for Rett syndrome. This therapy is notable for delivering the full-length human MECP2 gene, utilizing Neurogene's proprietary EXACT technology. This technology offers a critical advancement in gene therapy for Rett syndrome by enabling controlled transgene expression levels, thus avoiding toxic effects associated with overexpression.

The FDA’s selection of NGN-401 as one of the three Center for Biologics Evaluation and Research (CBER) programs for the START Pilot Program reflects its potential. Previously, NGN-401 received multiple designations from the FDA, including orphan drug designation, Fast Track designation, and rare pediatric designation. Additionally, it has been granted orphan designation and advanced therapy medicinal product designation from the European Medicines Agency (EMA) and the Innovative Licensing and Application Pathway (ILAP) designation from the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Neurogene is committed to developing innovative treatments for severe neurological diseases, aiming to improve the quality of life for patients and their families. The company focuses on overcoming the limitations of conventional gene therapy for central nervous system disorders. Their proprietary EXACT transgene regulation platform technology enables the delivery of therapeutic levels of transgenes while minimizing toxicity. Neurogene's advanced gene therapy manufacturing facility in Houston, Texas, ensures the production of CGMP-grade NGN-401, supporting its pivotal clinical development activities.

Overall, the inclusion of NGN-401 in the FDA's START Program marks a significant step forward in developing a potentially transformative treatment for Rett syndrome, fostering hope for affected patients and their families.