Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial.

Abstract

Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy that is often treatment resistant. Efficacy and safety of add-on cannabidiol (CBD) to treat seizures associated with LGS was demonstrated in two randomized controlled trials (RCTs). Patients who completed the RCTs were invited to enroll in this long-term open-label extension (OLE) trial, GWPCARE5 (NCT02224573). We present the final analysis of safety and efficacy outcomes from GWPCARE5. Patients received plant-derived highly purified CBD (Epidiolex in the United States; Epidyolex in the European Union; 100mg/ml oral solution), titrated to a target maintenance dose of 20mg/kg/day over 2weeks. Based on response and tolerability, CBD could then be reduced or increased up to 30mg/kg/day. Of 368patients with LGS who completed the RCTs, 366(99.5%) enrolled in this OLE. Median and mean treatment duration were 1090 and 826days (range = 3-1421), respectively, with a mean modal dose of 24mg/kg/day. Adverse events (AEs) occurred in 96% of patients, serious AEs in 42%, and AE-related discontinuations in 12%. Common AEs were convulsion (39%), diarrhea (38%), pyrexia (34%), and somnolence (29%). Fifty-five (15%) patients experienced liver transaminase elevations more than threetimes the upper limit of normal; 40(73%) were taking concomitant valproic acid. Median percent reductions from baseline ranged 48%-71% for drop seizures and 48%-68% for total seizures through 156weeks. Across all 12-week visit windows, 87% or more of patients/caregivers reported improvement in the patient's overall condition on the Subject/Caregiver Global Impression of Change scale. Long-term add-on CBD treatment had a similar safety profile as in the original RCTs. Sustained reductions in drop and total seizure frequency were observed for up to 156weeks, demonstrating long-term benefits of CBD treatment for patients with LGS.