Neurogene Inc. (Nasdaq: NGNE), a clinical-stage biotechnology company focused on developing genetic medicines for rare neurological diseases, today reported positive interim results from the first four participants in the low-dose cohort of its ongoing Phase 1/2 open-label clinical trial evaluating NGN-401 gene therapy for Rett syndrome. The data, collected from pediatric patients treated with a low dose of NGN-401, shows promising safety and efficacy outcomes, marking a significant milestone for both Neurogene and the Rett syndrome community.
Positive Interim Efficacy Data
The first four participants, aged 4 to 7 years, demonstrated notable improvements in key clinical areas, including hand function, language/communication, and motor skills—core domains typically affected by Rett syndrome. These gains were achieved despite the natural history of the disease, where such improvements are not expected.
- All participants were rated as “much improved” (score of 2) on the Clinical Global Impression Scale of Improvement (CGI-I), a measure of overall treatment effectiveness. A score of 2 is considered clinically meaningful.
- Participants showed 28-52% improvements on the Rett Syndrome Behavior Questionnaire (RSBQ), a caregiver-reported tool assessing Rett syndrome behaviors.
- Developmental milestones were achieved across multiple domains, including hand function, speech, and motor skills, with improvements continuing over time.
Rachel McMinn, Ph.D., Founder and CEO of Neurogene, expressed her excitement: “Today marks an important day for Neurogene and the Rett syndrome community. The interim data from the low-dose cohort is incredibly encouraging, as the first four participants showed significant gains in skills and developmental milestones that would typically not be expected given the natural progression of Rett syndrome.”
Safety Data
The low-dose and high-dose NGN-401 treatments have been well tolerated in the first seven participants (five in the low-dose cohort and two in the high-dose cohort), with no serious adverse events (SAEs) related to the treatment.
- No signs of MeCP2 overexpression toxicity were observed, a key concern in gene therapies for Rett syndrome.
- Most treatment-related adverse events (AEs) were typical of AAV-based gene therapies and were managed effectively with steroids. These events have either resolved or are resolving.
- No seizures or intracerebroventricular (ICV)-related AEs were reported.
However, Neurogene noted an emerging treatment-related SAE in one high-dose participant, consistent with known risks of AAV gene therapy. The company is continuing to monitor the situation.
Expanding the Trial
Neurogene has now initiated a new adolescent/adult cohort (Cohort 3) for NGN-401 to assess the therapy’s potential in a broader population, including individuals aged 16 and older, at the high dose. This will provide further insights into the treatment’s effectiveness and safety in a more mature patient group.
FDA Alignment and Manufacturing Progress
In addition to these promising clinical results, Neurogene has received FDA alignment on its potency assay strategy for NGN-401, a critical step toward initiating a registrational trial. The FDA has also agreed to Neurogene’s plans for scaling up manufacturing of NGN-401 to support a potential commercial launch.
Upcoming Milestones
- Enrollment completion for the low-dose pediatric cohort (N=8) is expected by Q4 2024.
- The company plans to update the public on the registrational trial design in early 2025.
- Additional interim data from the Phase 1/2 trial will be released in the second half of 2025.
Update on CLN5 Batten Disease Program
Neurogene also provided an update on its NGN-101 gene therapy program for CLN5 Batten disease, announcing that it will not be advancing the program further at this time. The company had submitted a Regenerative Medicine Advanced Therapy (RMAT) application to the FDA, but the application was denied. Neurogene is currently assessing next steps for this program.
About NGN-401
NGN-401 is an investigational AAV9-based gene therapy designed to treat Rett syndrome by delivering a full-length MECP2 gene, using Neurogene’s proprietary EXACT™ transgene regulation technology. The therapy aims to restore normal MECP2 levels without the risk of toxic overexpression, a challenge in conventional gene therapies for Rett syndrome.
NGN-401 has received several key designations from the FDA, including Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy (RMAT) status. The therapy has also been granted orphan designation by the European Medicines Agency (EMA) and Advanced Therapy Medicinal Product designation by the UK Medicines and Healthcare products Regulatory Agency (MHRA).
About Neurogene
Neurogene is committed to developing innovative genetic therapies for rare neurological diseases. With its EXACT™ transgene regulation platform, the company is advancing gene therapies that precisely deliver therapeutic levels of transgenes while minimizing toxicity. Neurogene’s state-of-the-art cGMP manufacturing facility in Houston, Texas, supports the production of NGN-401 and will be crucial for the company’s future clinical and commercial activities.
