Neurogene Reports Positive Interim Data for Rett Syndrome Gene Therapy

Rare Daily Staff

Neurogene said updated interim clinical data from the pediatric cohort in its ongoing Phase 1/2 study of NGN-401, its experimental gene therapy for females with Rett syndrome, show that all participants gained developmental milestones or experienced functional improvements, with durability and continued skill acquisition over time.

The company said those improvements occurred regardless of baseline disease severity.

Rett syndrome is a complex condition caused by a mutation in the MECP2 gene. It is characterized by a period of normal development until 6 to 18 months of age, followed by significant developmental regression and loss of acquired communication skills and purposeful hand use. Symptoms may also include hand stereotypies, such as hand wringing or clapping, and gait abnormalities.

NGN-401 is an investigational AAV9 gene therapy being developed as a one-time treatment for Rett syndrome. It is the first clinical candidate to deliver the full-length human MECP2 gene under the control of Neurogene’s EXACT transgene regulation technology. EXACT technology represents an advancement in gene therapy for Rett syndrome, which requires targeted MECP2 transgene expression without overexpression-related toxicity seen with conventional gene therapy.

The U.S. Food and Drug Administration selected NGN-401 for its START Pilot Program. The therapy has also received Regenerative Medicine Advanced Therapy, orphan drug, Fast Track, and rare pediatric disease designations from the FDA. In Europe, NGN-401 has been granted Priority Medicines (PRIME), orphan, and advanced therapy medicinal product designations by the European Medicines Agency, as well as Innovative Licensing and Access Pathway designation from the United Kingdom’s Medicines and Healthcare products Regulatory Agency.

At the 1E15 vg dose, NGN-401 has been generally well tolerated, with a favorable safety profile in both the pediatric and adolescent/adult cohorts.

“These skill gains far exceed the bar for our Embolden registrational trial, and coupled with NGN-401’s tolerability profile at the 1E15 vg dose, create the potential for a best-in-class gene therapy for Rett syndrome,” said Rachel McMinn, founder and CEO of Neurogene. “It is gratifying to see the benefits of our strategy to use local delivery to the brain, coupled with the naturally occurring full-length human gene, as a key to unlocking meaningful efficacy in this devastating disorder. Moreover, we are the only company evaluating a gene therapy in children with Rett syndrome as young as 3 years old in a single trial, which provides us an efficient path to market and first-in-class potential.”