Stiripentol Reduces Seizure Burden in Patients with Lennox-Gastaut Syndrome, Study Shows

Findings from a single-blind, multicenter phase 2 study in France indicated that Stiripentol (Diacomit; Biocodex), an antiseizure medication (ASM) originally developed as a treatment for Dravet Symptom (DS), can reduce seizure burden in patients with Lennox-Gastaut Syndrome (LGS).¹

Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-8, in Atlanta, Georgia, the trial enrolled 15 participants aged 2-20 years (mean age 9.1 [SD, 6.1]) with inadequately controlled LSG, defined as at least one seizure per week. Efficacy endpoints included change in seizure frequency and longest seizure-free interval.

During a 1 month baseline period, participants were permitted up to 3 concomitant ASMs as long as dosing remained stable. Participants then received placebo for one month, followed by stiripentol (2,000–3,000 mg/day, adjusted for age) for two months. Seizure types recorded included tonic-clonic, absence, drop, and sleep-related seizures. Study visits occurred on Day 0 (inclusion), Day 30 (end of baseline), Day 60 (end of placebo), Day 90, and Day 120 (end of the stiripentol phase).

Results showed that the antiseizure treatment produced a significant 81% median reduction compared to baseline (P = 0.016), with consistent improvements across seizure types: tonic (-88%), absence (-100%), drop seizure (-100%) and sleep-related (-100%). In contrast, the placebo period resulted in a non-significant 9% median reduction in total seizures. One patient had missing data (day 30); thus, 14 patients were evaluated for efficacy. By day 120, 5 patients (36%) were seizure-free, and three others experienced 75 to 100% reduction in seizure frequency.

The median longest seizure-free interval increased non-significantly from 60 hours at baseline to 80 hours after placebo, and then significantly to 376 hours following stiripentol treatment (P = 0.02 vs. placebo). From a safety perspective, no serious treatment-related adverse events (TEAEs) occurred. The most common side effects were somnolence, decreased appetite, and gastrointestinal disorders.

READ MORE: US Survey Reveals Underuse of Dravet Syndrome–Specific Antiseizure Medications in the Clinic

Previously, Stiripentol had been tested for its clinical profile outside the sphere of just a treatment for DS. In addition to seizure burden reduction, data from the STIRUS study, an retrospective, observational trial, indicated that real-world treatment with stiripentol was linked to fewer status epilepticus episodes and lower healthcare utilization in patients with DS.²

The analysis was comprised of 98 patients with a confirmed DS who initiated stiripentol after August 2018 and received it for at least 3 months following. data was extracted 3 months prior to treatment initiation, the first 3 months of treatment, and the final 3 months of stiripentol, irrespective of treatment discontinuation.

Treatment with the FDA-approved product led to significant reductions in bilateral convulsive seizures (BCS; OR, 2.16; 95% CI, 1.25-3.75; P <.006). In addition, investigators found that the number of patients experiencing status epilepticus (SE) decreased from 33 at baseline to 16 and 14 during the first and final 3 months, respectively (ORs, >2.8; P <.003). Overall, the longest episode lasted a median of 15 minutes.

REFERENCES
1. Auvin S, Serraz B, Lespinasse J, et al. Stiripentol Use in Lennox-Gastaut Syndrome: Results from a Phase 2 Clinical Trial. Presented at: 2025 AES Annual Meeting; December 5-9; Atlanta, Georgia.
2. Wirrell E, Wheless J, Perry MS, et al. Real-World Use and Effectiveness of Stiripentol in U.S. Patients with Dravet Syndrome: Results from the STIRUS Study. Presented at: 2025 AES Annual Meeting; December 5-9; Atlanta, GA. Abstract 1.386