Assess the long-term safety and efficacy of add-on CBD treatment in patients with Dravet syndrome (DS) in the second interim analysis of the open-label extension (OLE) of two Phase 3, randomized controlled trials, GWPCARE1 and GWPCARE2.

DS is an intractable epilepsy, with onset typically in the first year of life and a high mortality rate. Highly purified CBD (Epidiolex^®) is approved in the U.S. for seizures associated with Dravet Syndrome in patients ≥2 years of age.     

Patients received GW’s plant-derived pharmaceutical formulation of highly purified CBD (100 mg/mL) in oral solution. The primary endpoint was safety. Secondary endpoints were change from baseline in convulsive and total seizure frequency and Subject/Caregiver Global Impression of Change.

Of 289 patients who completed the randomized controlled trials, 278 enrolled in GWPCARE5. At data cut-off, 14% of patients had completed, 52% were ongoing, and 34% had withdrawn. Mean patient age was 9.8 years; 97% were <18 years. Patients were taking a median of 3 concurrent antiepileptic drugs with 68% taking clobazam, 63% valproate, and 39% stiripentol. The mean of patients’ modal CBD dose was 22 mg/kg/d. Adverse events (AEs) and serious AEs were reported by 96% and 32% of patients; 7% discontinued due to AEs. Elevated liver transaminases >3× upper limit of normal were reported in 9% of patients; none had severe liver injury. Two nontreatment-related deaths were reported. Median % reductions from baseline assessed in 12-week intervals were 44%-57% for convulsive and 49%–67% for total seizures through 72 weeks. Over 80% of patients/caregivers reported improvements in overall condition.

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