Embolden gene therapy trial finishes dosing ahead of schedule

All 25 participants in the Phase 3 Embolden study have received their doses of NGN-401, Neurogene’s experimental gene therapy for Rett syndrome, surpassing the trial’s initial enrollment target ahead of schedule.

“We are pleased to have completed dosing in the Embolden trial of NGN-401 within our original timeline while exceeding our enrollment target, reflecting both the significant unmet need and strong demand from the Rett syndrome community,” Rachel McMinn, PhD, founder and CEO of Neurogene, said in a company press release. “This milestone brings us one step closer to delivering a potential best-in-class, one-time treatment for Rett syndrome.”

Recommended Reading

May 8, 2026 by Neil Genzlinger

The day a famous actress joined girls with Rett syndrome in Washington

Next steps for NGN-401 clinical trials

Neurogene expects top-line results for Embolden (NCT05898620) in the second half of 2027. If successful, the results could support a Biologics License Application (BLA) requesting approval of NGN-401 for Rett syndrome.

The company also anticipates releasing updated results from an ongoing Phase 1/2 study of NGN-401 in the coming weeks.

Rett is a neurodevelopmental disorder that primarily affects girls and women. Mutations in the MECP2 gene, which is important for nerve cell health, brain development, and regulating which genes are turned on or off, cause most cases of the condition.

Neurogene designed NGN-401 to deliver a functional copy of MECP2 to brain cells. The one-time gene therapy, which uses engineered viruses to carry the genetic material, is injected into the brain’s fluid-filled cavities while the patient is under anesthesia. The treatment aims to prevent abnormally high MeCP2 levels, which may lead to toxic side effects.

Interim results of the Phase 1/2 trial shared late last year showed that girls who received NGN-401 at a dosage of 1E15 (one quadrillion) vector genomes (vg) experienced functional improvements. These included reaching new developmental milestones or gaining skills in hand function, communication, and gross motor function.

Embolden is a multi-center registrational trial, meaning its data could provide the basis for regulatory approval of NGN-401. It will assess the efficacy, safety, and tolerability of NGN-401 at 1E15 vg in females with Rett, who are 3 years and older.

Initially, Neurogene planned to enroll 20 girls and women. However, the trial ultimately enrolled 25 participants, all of whom have received the gene therapy. According to Neurogene, the participants have tolerated the dosage well so far.

One participant in the earlier trial experienced hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening complication that may occur with therapies using viral vectors. This occurred at a higher dose than that received by the Embolden participants. None of the Embolden participants has shown signs of HLH.

The trial’s primary goal is to evaluate the proportion of patients who respond to the therapy after one year of follow-up. This criterion includes attaining a Clinical Global Impression-Improvement (CGI-I) scale score of 3 or less, and gaining at least one developmental milestone from a pre-specified list. The CGI-I assesses clinicians’ perspectives on improvement.

“We are deeply grateful to the participants, their families and the investigators for their trust, partnership and ongoing support of the development of NGN-401,” McMinn said. “We look forward to sharing topline results from Embolden in the second half of 2027 and advancing NGN-401 towards a planned BLA submission.”

NGN-401 has received several regulatory designations that incentivize and potentially accelerate the development of promising therapies. In the U.S., these include participation in the Support for Clinical Trials Advancing Rare Disease Therapeutics program and receiving regenerative medicine advanced therapy status, along with breakthrough therapy, fast track, orphan drug, and rare pediatric disease designations.