Neurogene halts high-dose Rett syndrome therapy after adverse event

Neurogene has provided an update on its Phase 1/2 clinical trial for NGN-401, a gene therapy targeting Rett syndrome, after a serious adverse event (SAE) was reported in a participant.

The participant, dosed at 3E15 vg (high-dose cohort), experienced a severe hyperinflammatory syndrome and remains in critical condition. This rare immune response has been associated with high-dose exposure to adeno-associated virus (AAV) therapies.

Following the SAE, Neurogene paused dosing in the high-dose cohort and engaged with the FDA under the START program.

The FDA allowed the trial to proceed with the 1E15 vg (low-dose) cohort but prohibited further enrollment in the high-dose group. Neurogene is revising its trial protocol to reflect this change and no longer expects to complete enrollment in the low-dose cohort by the end of 2024.

To date, no other treatment-related SAEs have been reported in the trial, including among five participants in the low-dose cohort and two previously dosed in the high-dose cohort. All treatment-related adverse events (AEs) in the low-dose group have been mild, steroid-responsive, and either resolved or resolving.

There have been no signs of MeCP2 overexpression toxicity or complications from intracerebroventricular (ICV) procedures.