Authors :
Presenting Author: James Wheless, BScPharm, MD, FAAP, FACP, FAAN, FAES, FCNS – University of Tennessee Health Science Center and Le Bonheur Children's Hospital
Delphine Vandame, PhD – Biocodex
Laurent Chancharme, PharmD, PhD – Biocodex R&D center, Compiègne, France
Rationale:
Stiripentol (STP), approved for the treatment of seizures associated with Dravet syndrome, has shown efficacy in other drug-resistant developmental and epileptic encephalopathies (DEEs). We conducted a literature review to evaluate the broader efficacy and tolerability profile of STP across syndromic and genetic epilepsies.
Methods:
Twelve clinical sources were analyzed, comprising 1 randomized trial, 4 observational cohort studies and 7 case reports or series. All clinical sources exclusively involving DS populations were excluded. Syndromes covered included Lennox–Gastaut syndrome (LGS), epilepsy with myoclonic atonic seizures (EMAtS) (formerly Doose Syndrome), epilepsy of infancy with migrating focal seizures (EIMFS), tuberous sclerosis complex (TSC), and genetically defined DEEs such as SLC6A1-, SLC13A5-, PCDH19- and CNTNAP2-related syndromes. Key outcomes evaluated were ≥50% seizure reduction (responder rate), seizure freedom, adverse events (AEs), and treatment discontinuation.
Results:
Data from 417 patients across the 12 references were analyzed:
- The median dose of STP was 38 mg/kg/day (range: 4-100 mg/kg/day), with a median patient age of 5 years (range: 2 months to 21 years)
- Reported responder rates ranged from 46% to 100%. Aggregated data showed
- 46-68% in the randomized clinical trial and the observational cohorts,
- and 100% response (seizure-freedom) in monogenic syndromes (SLC6A1, SLC13A5, PCDH19) and in EIMFS.
- Complete cessation of seizures was reported in patients treated with 38-77 mg/kg/day of STP:
- in SLC6A1 (n=1/1, 24 months), PCDH19 (n=1/ 1, 34 months), SLC13A5 (n=3/3, 18 months), EIMFS (n=4/5, with n=2, >12 months),
- STP was effective in resolving refractory status epilepticus (RSE) or seizure clusters in 4/4 patients with DEE (including 2 with LGS), with resolution within 0.3 to 2 days at a median dose of 50 mg/kg/day.
- STP showed broad-spectrum efficacy across multiple seizure types, including generalized tonic-clonic, absence, myoclonic, tonic, focal, and epileptic spasms. Cognitive and behavioral improvements were observed in over 50% of patients, when assessed.
- AEs were reported in 19–48% of cases, most commonly drowsiness, ataxia and anorexia. Treatment discontinuations due to AEs remained low (≤5%) in most series, with slightly higher rates observed in adults or when dose was >75mg/kg/day.
Conclusions:
STP demonstrates consistent efficacy and acceptable tolerability across a wide spectrum of non-Dravet DEEs, including ultra-rare genetic forms. Its effectiveness across seizure types and in RSE supports its consideration as a treatment option in complex drug-resistant epilepsy. Prospective, genotype-driven studies are warranted to better define the optimal use of STP in DEEs.
Funding:
Funding: Biocodex, Inc.