Epilepsy affects ~50 million worldwide, with a significant number experiencing uncontrolled seizures despite antiseizure medications (ASMs). While sodium channel blockers (SCBs) are a cornerstone of ASM therapy, approved medications have limited efficacy and dose-limiting side effects. Vormatrigine is a functional state modulator precisely targeting the hyperexcitable state of sodium channels shown to achieve higher therapeutic concentrations with superior tolerability compared to other sodium channel therapies, without the need for titration.

RADIANT (NCT06908356) is an open-label Phase 2 clinical trial enrolling up to 80 participants aged 18-75 years with FOS or idiopathic PGTS based on ILAE classification. Participants received vormatrigine 30mg daily for 8 weeks. The study consisted of Screening/Observation (Baseline), Treatment and Follow-up periods. The primary endpoint was median percent change in monthly (28-day) seizure frequency from Baseline to Week 8.

Within the initial evaluable cohort of 37 subjects with FOS, overall median percent reduction in focal seizure frequency from baseline to Week 8 was 56.3%, with more than 20% of participants achieving seizure freedom during the last month of treatment, and 54% achieving ≥50% response in Week 1 and 67% in Week 8. Vormatrigine demonstrated consistent efficacy across background ASMs (including ~30% on cenobamate), baseline seizure burden and seizure subtypes.

Most TEAEs were mild-to-moderate and transient. The few severe and serious AEs all resolved. Approximately 20% of subjects discontinued the trial; in 6 cases where investigators reduced background ASM therapy, AEs were successfully managed, with no discontinuation observed.

These results build on vormatrigine data to date, positioning it as a fast-acting, precision once-daily ASM with minimal drug–drug interactions and a favorable safety profile. Completed RADIANT study findings are anticipated to further support advancement of the vormatrigine ENERGY program.