Authors :
Presenting Author: Stéphane Auvin, MD, PhD – Center for rare epilepsies, Pediatric Neurology Dpt, Robert-Debré Hospital, Paris, France
Benjamin Serraz, PharmD, PhD – Biocodex Orphan Disease Division, Gentilly, France
Jérémie Lespinasse, PharmD, PhD – eXYSTAT, Malakoff, France
Laurent Chancharme, PharmD, PhD – Biocodex R&D center, Compiègne, France
Rationale:
During the clinical development of stiripentol, an exploratory Phase 2 trial was conducted in patients with Lennox-Gastaut Syndrome (LGS). As stiripentol was subsequently developed for Dravet syndrome, results of the LGS trial have remained unpublished and are presented here for the first time.Methods:
Patients aged 2–20 years with inadequately controlled LGS (≥1 seizure/week) were enrolled in a single-blind, multicenter Phase 2 study in France. After a 1-month baseline period with stable treatment (up to 3 concomitant antiseizure medications [ASMs]), patients received placebo for 1 month, followed by stiripentol (2,000–3,000 mg/day, age-adjusted) for 2 months. Seizure frequency and types (tonic-clonic, absence, drop seizures, sleep-related seizures) were recorded by caregivers in diaries. Study visits were at Day 0 (inclusion), Day 30 (baseline end), Day 60 (end of placebo), Day 90, and Day 120 (end of stiripentol phase). Efficacy endpoints included change in seizure frequency and longest seizure-free interval (maximum duration between seizures).Results:
Fifteen patients (mean age 9.1 ± 6.1 years) were included. They received an average of 3 ASMs, most commonly valproate (n=10) and clobazam (n=8). Median monthly seizure count at baseline was 35 (range: 4–203), with tonic and absence seizures being most common. One patient had missing data (day 30); thus, 14 patients were evaluated for efficacy. At the end of the placebo period, a non-significant 9% median reduction in total seizures was observed. In contrast, stiripentol treatment led to 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%). Five patients (36%) were seizure-free at Day 120, and three others had a [75–100%[ reduction. Median longest seizure-free interval increased non-significantly from 60 hours at baseline to 80 hours after placebo, then significantly to 376 hours after stiripentol (p=0.02 vs. placebo). From a safety perspective, no serious treatment-related adverse events occurred. The most common side effects were somnolence, decreased appetite and gastrointestinal disorders.Conclusions:
Despite the small sample size, stiripentol appeared to reduce seizure burden in LGS patients. These promising results support further investigation in a larger, controlled trial.Funding: This study was funded by Biocodex