To assess long-term safety and efficacy of add-on CBD in patients with Lennox-Gastaut syndrome (LGS) in the third analysis of the open label extension (OLE; GWPCARE5) of two Phase 3, randomized controlled trials (RCTs), GWPCARE3 and GWPCARE4.

LGS is an epileptic encephalopathy that is often treatment resistant. Efficacy of CBD was demonstrated in the RCTs, with an acceptable safety profile.

Patients who completed either of the RCTs could enter this OLE trial (GWPCARE5/NCT02224573). Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution). Primary endpoint: safety. Secondary efficacy endpoints: median percentage change from baseline in drop and total seizure frequency.

Overall, 99% (366/368) of eligible patients with LGS entered the OLE. Median follow-up was 150 weeks (3 days to 179 weeks); 119 patients (33%) withdrew. Mean age: 16 years; 33% ≥18 years; 54% male. Baseline median seizure frequency/28 days: 80 drop seizures; 168 total seizures. During the extended follow-up, the incidence of adverse events (AE) was 96%; serious AEs 42%; AEs leading to discontinuation 12%. Most common AEs (≥20%): diarrhoea, convulsion, pyrexia, somnolence, vomiting, upper respiratory tract infection, and decreased appetite. AEs of alanine aminotransferase increased occurred in 8% of patients. There were 11 deaths; none deemed treatment-related by the investigator(s). Median percentage reductions in seizure frequency (12-week windows over 156 weeks) was 48–71% for drop seizures and 48–68% for total seizures.

Long-term treatment with add-on CBD in patients with LGS produced sustained seizure reductions, with no new safety concerns.