Neurogene/FDA alignment on pivotal trial

01/07/2025

Following Neurogene’s update at the recent IRSF Scientific Meeting in Boston, the company has now received written alignment from the U.S. Food and Drug Administration (FDA) to move forward with a pivotal (registrational) trial of NGN-401, their gene therapy candidate for Rett syndrome.

🔍 While Phase 1/2 trials primarily assess safety, this pivotal study will focus more intensively on efficacy—whether the treatment meaningfully benefits participants—while continuing to collect safety data.

🔑 Key Takeaways:

👧 Eligibility, Numbers & Locations
  • The age range has been expanded from 4–10 years to 3 years and older.
  • The pivotal trial will include females only.
  • Neurogene is working with the FDA to determine the final number of participants—currently proposed at 18.
  • Trial site locations are still being finalised.
đź’‰ Dosing & Placebo
  • The dose used will be the lower 1E15 vector genomes (vg) dose, now standard in the ongoing Phase 1/2 trial.
  • The higher 3E15 dose has been discontinued.
  • No placebo group: all participants will receive the gene therapy.
  • Each participant will act as her own baseline, with progress compared to her pre-treatment state rather than to a control group.
🎯 Efficacy Endpoints

The primary efficacy measure has two parts:

  1. Clinical Global Impression–Improvement (CGI-I) scale
    – Assesses overall change in functioning using Rett-specific anchors.
    – Each point shift represents a significant change.
  2. Gain of Developmental Milestone
    – From a set of 28 key skills typically rarely regained after age 6 in untreated individuals with Rett syndrome.
    – Assessed via video analysis of before and after the patient receives treatment.

Read the full press release here

Read the Neurogene community letter below

our-letter-to-rett-syndrome-community-06302025Download

In Summary ✨

This is another encouraging step forward from Neurogene. FDA alignment at this stage enables a smoother transition into the pivotal trial.

Importantly, Neurogene is working to include an additional 6-month efficacy endpoint, alongside the already agreed 12-month endpoint, in an effort to accelerate the path to market. ⏩

Finally, the company has expressed gratitude to all families who participated in the ‘Burden of Disease’ surveys—shared by Reverse Rett through the Rett Registry UK—for helping lay the groundwork for this progress. 🙏 Rett Registry UK.