Cannabidiol Efficacy in Patients With Lennox-Gastaut Syndrome With Developmental and Epileptic Encephalopathy-Associated Genetic Variants: A Subgroup Analysis
Abstract number :
1.382
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2025
Submission ID :
954
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Elizabeth Thiele, MD, PhD – Massachusetts General Hospital
Michael Boffa, MD, FAES – Jazz Pharmaceuticals, Inc.
Daniel Checketts, MSc – Jazz Pharmaceuticals, UK Ltd.
Farhad Sahebkar, MD – Jazz Pharmaceuticals, Inc.
Rationale: Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy (DEE) characterized by distinct electroclinical characteristics that may overlap with DEEs of genetic etiologies. Cannabidiol (CBD; Epidiolex®, 100 mg/mL oral solution) is FDA approved for the treatment of seizures associated with LGS, Dravet syndrome, and tuberous sclerosis complex in patients ≥ 1 year of age. CBD safety and efficacy in patients with LGS were demonstrated in two placebo-controlled clinical trials, GWPCARE3 (NCT02224560) and GWPCARE4 (NCT02224690), and open-label extension trial GWPCARE5 (NCT02224573). Due to the rarity of genetic DEEs, controlled trial data in these patient populations are limited. This post hoc analysis evaluated the efficacy of CBD in a subgroup of participants in the LGS placebo-controlled clinical trials with genetically confirmed DEEs.
Methods: All participants met clinical diagnostic criteria for LGS including documented history of a slow (< 3.0 Hz) spike-and-wave electroencephalogram and evidence of ≥ 2 types of generalized seizures, including drop seizures, for ≥ 6 months. Participants with documented genetic variants in their clinical histories were identified, and all identified variants were searched in the Genes4Epilepsy database. For variants linked to a DEE or progressive myoclonic epilepsy phenotype, manual literature searches were performed to identify those associated with named syndromes. Efficacy endpoints included change in drop seizure frequency from baseline and Global Impression of Change (GIC). Safety analyses included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), treatment-related TEAEs and SAEs, and withdrawals.
Anti-seizure Medications