To evaluate the efficacy of highly purified cannabidiol (CBD; Epidiolex^® [US]/Epidyolex^® [EU], 100 mg/mL oral solution) in a subgroup of randomized clinical trial (RCT) participants with genetic developmental and epileptic encephalopathies (DEEs) in addition to Lennox-Gastaut syndrome (LGS).

LGS is a severe DEE characterized by distinct electroclinical characteristics that may overlap with DEEs of genetic etiologies. CBD safety and efficacy in patients with LGS were demonstrated in 2 placebo-controlled RCTs and an open-label extension trial. Controlled trial data in individuals with genetic DEEs are limited; hence, this post hoc analysis assessed these data from CBD RCTs.

All RCT participants met clinical diagnostic criteria for LGS. Participants with documented genetic variants in their clinical histories were identified. All identified variants were searched in the Genes4Epilepsy database; for variants linked to a DEE/progressive myoclonic epilepsy phenotype, literature searches were performed to identify associations with named syndromes. Efficacy endpoints included change in drop seizure frequency from baseline. Safety analyses included treatment-emergent adverse events (TEAEs), serious AEs (SAEs), treatment-related (TR)-AEs, TR-SAEs, and withdrawals.

We identified 53 participants aged 2–55 years who had a confirmed/likely genetic DEE in addition to LGS (CBD 10 mg/kg/day [CBD10], n=6; CBD 20 mg/kg/day [CBD20], n=25; placebo, n=22). Participants with genetic DEEs had broadly similar demographic characteristics and baseline seizure frequency compared with the overall RCT populations. In participants with genetic DEEs randomized to CBD20, median decrease in drop seizure frequency from baseline was −48.6% vs −16.3% in the placebo group. The results were consistent with the RCTs overall. TEAEs were reported in 90.3% of participants with genetic DEEs who received CBD vs 90.9% in the placebo group; 1 TR-SAE was reported in the CBD20 group.