2026 American Academy of Neurology Abstract Website

Objective:

Evaluating the efficacy, safety, and pharmacokinetics of vormatrigine in adults with focal onset seizures (FOS).

Background:

FOS is characterized by localized neuronal hyperexcitability, with current standard-of-care limited by tolerability issues and need for titration to avoid side effects. Vormatrigine, a precision functional state modulator targeting the hyperexcitable state of sodium channels, is currently in development for adult FOS and generalized epilepsy. Recent data highlight a superior preclinical and early clinical profile compared to currently approved antiseizure medications (ASMs), demonstrating a favorable safety and tolerability profile in doses up to 45 mg, with no clinically significant food effect. Notably, emerging data demonstrate its ability to significantly exceed therapeutic concentrations while being well tolerated, without the need for titration.

Design/Methods:

POWER1 is a global, multicenter, double-blind, parallel design Phase 2/3 study enrolling ≈230 participants aged 18-75 years with FOS, currently taking 1-3 concomitant ASMs. Participants are randomized 1:1 to receive vormatrigine QD, at 20 mg for the first 6 weeks and 30 mg for the second 6 weeks, or matching placebo for 12 weeks. The study will consist of Screening/Observation (Baseline), Treatment and Follow-up periods.

Results:

The primary endpoint is median percent change in monthly (28 days) focal seizure frequency from the Baseline Period to the Treatment Period for vormatrigine compared to placebo. Key secondary endpoints include the proportion of subjects experiencing a ≥50% reduction in monthly focal seizure frequency (responder rate) from the Baseline Period to the Treatment Period for vormatrigine compared to placebo. Further secondary and exploratory endpoints examine the effect of vormatrigine on additional efficacy and safety outcomes, including pharmacokinetic characterization of plasma concentrations of vormatrigine. Enrollment is ongoing with topline data anticipated by year end 2025.

Conclusions:

Expanding on preclinical and preliminary clinical data, the POWER1 study examines the efficacy, safety and pharmacokinetics of vormatrigine as an ideal precision ASM for FOS.