Assess the long-term safety and efficacy of add-on CBD treatment in patients with Dravet syndrome (DS) in the third analysis of the open-label extension (OLE; GWPCARE5 [NCT0224573]) of two randomized controlled trials (RCTs), GWPCARE1 (Phase 2/3) and GWPCARE2 (Phase 3).

DS is a developmental and epileptic encephalopathy that is often treatment-resistant, with onset by 15 months and a high mortality rate.

Patients initially received 20 mg/kg/day plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution); the dose could be decreased or increased to 30 mg/kg/day at the investigator’s discretion. Primary endpoint: safety. Secondary efficacy endpoints: median percentage change from baseline in convulsive and total seizure frequency.

Of 330 patients who completed RCTs, 315 enrolled in GWPCARE5. At data cut-off, the OLE was ongoing and 43% of patients had withdrawn. Mean patient age was 10 years; 97% <18 years. Patients were taking a median of 3 concurrent antiepileptic drugs at baseline; during the OLE, 68% were taking clobazam, 67% valproate, and 38% stiripentol. Mean modal CBD dose was 22 mg/kg/day. Adverse events (AEs) and serious AEs occurred in 97% and 41% patients, respectively; 9% discontinued due to AEs. AEs of increased aspartate aminotransferase occurred in 12% of patients. Four deaths occurred (considered nontreatment-related by the investigator). Median percentage reductions in seizure frequency overall (12-week windows over 156 weeks) was 45%-73% for convulsive and 49%–80% for total seizures.

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