Neurogene Accelerates Enrollment in Rett Syndrome Gene Therapy Trial

Neurogene, a clinical-stage company specializing in genetic medicines for rare neurological diseases, is advancing its Phase 1/2 clinical trial for NGN-401, a gene therapy for Rett syndrome in female pediatric patients. The trial has been expanded to include additional participants in the initial dosing group and the introduction of a higher dosage cohort. This modification is anticipated to yield a more comprehensive dataset, which will guide the design of future trials aimed at regulatory approval.

The company has successfully dosed a third patient in Cohort 1 and aims to complete dosing for this group in the latter half of 2024, thanks to the removal of a staggered dosing approach. The U.S. clinical protocol for NGN-401 has been amended to increase the number of patients in Cohort 1 from five to eight, with parallel dosing for the remaining participants. Additionally, a new Cohort 2 has been introduced, targeting eight patients with a higher total vector genome dose delivered via intracerebroventricular administration.

The first three patients in the new cohort will receive treatment in a staggered manner, with the first dosing expected in the second quarter of 2024. Following a review by the Data and Safety Monitoring Board, the protocol will permit parallel enrollment for the remaining patients in Cohort 2. To mitigate potential immune responses associated with adeno-associated virus-based products, a targeted immunosuppression regimen has been included for Cohort 2, featuring rituximab, sirolimus, and a brief course of corticosteroids. Cohort 1 will continue with corticosteroids alone.

Neurogene's EXACT gene regulation platform is a key component of NGN-401, allowing for precise control of transgene expression levels to avoid toxicities linked with conventional gene therapy. The technology has demonstrated the capability to escalate dosage and enhance biodistribution to the brain without increasing MECP2 transgene expression to harmful levels.

The company has reported that NGN-401 has been well-tolerated in the trial so far, with no serious adverse events or signs of overexpression-related toxicity observed. Neurogene is on schedule to report interim clinical data from Cohort 1 in the fourth quarter of 2024, with further data from Cohort 2 expected in the second half of 2025.

Neurogene's mission is to develop innovative treatments for devastating neurological diseases, focusing on overcoming the limitations of traditional gene therapy. The company's approach includes optimizing delivery to target tissues and designing products for maximum potency and purity to ensure an effective and safe therapeutic profile. With a state-of-the-art gene therapy manufacturing facility in Houston, Texas, Neurogene is well-equipped to support the pivotal clinical development of NGN-401 and other potential treatments.