Pivotal trial tests new gene therapy approach for Rett syndrome
NGN-401 study moves closer to completing dosing
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A Phase 3 clinical trial testing the experimental gene therapy NGN-401 for Rett syndrome is underway and continuing to enroll participants, according to an update from its developer, Neurogene.
The Phase 3 study, called Embolden (NCT05898620), aims to test NGN-401 in 20 girls and young women with Rett syndrome, ages 3 and older. More than a dozen sites across the U.S. are participating in the trial, with 10 currently recruiting participants. According to Neurogene, multiple patients were dosed in late 2025, and the company expects to complete dosing in the second quarter of this year.
“We are pleased to share that multiple participants have been dosed in our Embolden registrational trial of NGN-401 gene therapy for Rett syndrome, an important step toward completing dosing in the second quarter,” Rachel McMinn, PhD, founder and CEO of Neurogene, said in a company press release.
How the Phase 3 trial is designed to measure benefit
All participants in the Embolden study will receive NGN-401, with the primary goal of determining how many show both a clinician-rated functional improvement and gain at least one developmental milestone or skill from a prespecified list of 28 that are typically not acquired by untreated people with Rett syndrome. If the results are positive, Neurogene plans to use the trial as the basis for seeking regulatory approval of NGN-401 as a Rett treatment. The company has also begun preliminary preparations for a potential commercial launch.
“As we rapidly advance NGN-401 towards commercialization, we are actively engaging with payors and other key stakeholders while leveraging our internal CMC [chemistry, manufacturing, and controls] capabilities for commercial-grade production to ensure future launch readiness,” McMinn said. “With cash runway expected through the first quarter of 2028, we believe we are well-positioned to advance NGN-401 through key upcoming milestones, including [submission of an application seeking approval in the U.S.], to achieve its potential as a best-in-class gene therapy for Rett syndrome.”
Rett syndrome is mainly caused by mutations in the MECP2 gene, which plays a critical role in brain cell health and function. NGN-401 is designed to deliver a working copy of MECP2 to brain cells, along with built-in controls intended to help regulate gene activity and avoid harmful overexpression. The therapy is administered directly into fluid-filled spaces of the brain using a procedure known as intracerebroventricular infusion.
What earlier trial results showed
Neurogene recently announced interim findings from a previous Phase 1/2 clinical trial testing NGN-401 in people with Rett syndrome. Ten participants received the dose that is now being evaluated in the Phase 3 study. The company reported that no serious side effects were observed in these 10 participants and that all showed functional improvements. Neurogene plans to report additional data from the early trial later this year, once all participants have been followed for at least 12 months after NGN-401 treatment.
“We continue to track the progress of the participants in our Phase 1/2 trial, with plans to report updated interim safety and efficacy data by mid-year, including at least 12 months of data for all participants,” McMinn said.
