Neurogene Inc. announced positive interim clinical data from its Phase 1/2 open-label trial of NGN-401 gene therapy for Rett syndrome in female pediatric patients. The low-dose cohort demonstrated a favorable safety profile and meaningful skills and developmental milestones improvements. These improvements were consistent across multiple assessment scales and exceeded expectations based on the natural progression of Rett syndrome.
Interim data from seven participants, five in the low-dose group and two in the high-dose group, indicate that both NGN-401 dosages are well-tolerated. However, a treatment-related serious adverse event, consistent with known risks of AAV gene therapy, occurred in the third high-dose participant.
Focusing on the four participants in the low-dose cohort (aged 4-7 years), assessments conducted 3 to 15 months post-dosing revealed consistent and durable advancements across key Rett syndrome measures. All participants showed a 2-point improvement on the clinician-rated Clinical Global impression improvement (CGI-I) scale. Improvements were also observed in the caregiver-completed Rett Syndrome Behavior Questionnaire (RSBQ), ranging from 28% to 52%. Furthermore, participants experiencing sleep disruptions, constipation, and dysphagia at baseline demonstrated objective improvements after treatment. These observed gains in skills and developmental milestones were sustained and deepened over time, contrasting with the typical disease course.
In addition to the pediatric cohort, Neurogene initiated an adolescent/adult cohort (Cohort 3) to assess NGN-401’s potential in a broader patient population. This cohort will enroll three participants aged 16 and older at the high dose.
The company also secured FDA alignment on its potency assay strategy for NGN-401, a critical step for initiating a registrational trial. The FDA also supports Neurogene’s manufacturing scale-up plans, paving the way for a potential commercial product launch. Neurogene aims to provide an update on the registrational trial design in the first half of 2025.
Regarding its CLN5 Batten disease program, Neurogene will not proceed with the NGN-101 gene therapy. This decision follows the FDA’s denial of the company’s Regenerative Medicine Advance Therapy (RMAT) application despite Neurogene’s belief that it met the required criteria. The company is currently evaluating options for this program.
NGN-401 utilizes Neurogene’s EXACT™ transgene regulation technology to deliver the full-length human MECP2 gene. This technology aims to provide therapeutic levels of MECP2 while mitigating overexpression-related toxicity often associated with conventional gene therapy. NGN-401 has received various designations from the FDA, including selection for the START Pilot Program, RMAT designation, orphan drug designation, Fast Track designation, and rare pediatric designation. It has also received designations from the European Medicines Agency (EMA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA).
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
