Neurogene initiated dosing of its NGN-401 pivotal Rett syndrome study in Q4 2025, with multiple patients already treated. The company expects to complete enrollment and dosing by Q2 2026 and to present updated Phase I/II data for 10 patients with at least 12 months of follow-up in mid-2026.

In eight participants, Phase I/II data showed a total of 35 developmental milestones gained, averaging about four new skills per patient. Improvements were characterized as multi-domain, durable and deepening over time, which Neurogene says reduces risk heading into the pivotal trial.

After observing hemophagocytic lymphohistiocytosis at a 3×10^15 vg dose in prior studies, the pivotal trial uses a lower 1×10^15 vg dose with enhanced ferritin and immune monitoring. No HLH events have been reported at this dose, and one transient nerve conduction abnormality resolved without intervention.

Neurogene’s “biology-first” approach uses a full-length MECP2 construct with proprietary expression control and in-house manufacturing targeting PPQ and commercialization. The FDA’s success threshold for Rett is 7/20 (35%), while Neurogene’s data suggest an ~80% response rate, with a U.S.-first BLA and commercial launch focus.