Rett gene therapy trial starts dosing patients
Embolden trial up and running at 12 sites, Neurogene says
The Embolden clinical trial, a registrational study testing Neurogene‘s gene therapy NGN-401 in people with Rett syndrome, has begun dosing participants.
“Dosing the first participant in the Embolden registrational trial of NGN-401 marks a major milestone in advancing a gene therapy for Rett syndrome,” Rachel McMinn, PhD, Neurogene’s founder and CEO, said in a company press release.
Neurogene said the Phase 3 trial (NCT05898620), which aims to test NGN-410 in 20 girls and women with Rett, ages 3 and older, is up and running at 12 of 13 planned sites. The company said it expects the trial to finish recruitment in the next three to six months.
All participants in the Embolden trial will be treated with NGN-401 at a dose of 1E15 (1,000 trillion) vector genomes, with the goal of assessing how the one-time therapy affects measures of development relative to the trial’s start. Treatment efficacy and safety will be tracked for three years, and each participant is expected to enroll in a long-term follow-up study lasting 12 years.
Trial results could lead to regulatory approvals
If the results are positive, Neurogene plans to use the study as a basis for applying for regulatory approvals of NGN-401. The U.S. Food and Drug Administration (FDA) agreed to important aspects of the trial’s design earlier this year, and in the months since, Neurogene has been preparing for its launch.
“We prioritized operational excellence this year, doubling our U.S. site footprint and initiating 12 of 13 sites to meet patient demand, positioning us to complete enrollment within the next three to six months,” McMinn said.
Rett is a genetic disorder that mainly affects girls, causing a wide range of developmental, motor, and behavioral symptoms. It’s mainly caused by mutations in the MECP2 gene, leading to reduced levels of a protein called MeCP2 that’s key for brain development.
NGN-401, which is administered directly into fluid-filled cavities in the brain via a one-time procedure, is designed to deliver a healthy version of the MECP2 gene to brain cells. The gene therapy includes molecular machinery to carefully modulate the gene’s activity, with the aim of restoring MeCP2 protein production without driving levels too high (which can cause other problems).
Embolden is a conversion of a Phase 1/2 study that finished dosing earlier this year and is ongoing to track outcomes. Early data from the first few participants showed patients gained new developmental milestones following NGN-401 treatment.
NGN-401 has shown promise in preclinical models, easing symptoms and improving survival in a mouse model of the disease.
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