Long-term efficacy and safety of cannabidiol in patients with treatment-resistant focal epilepsies treated in the Expanded Access Program.

Objective: Cannabidiol (CBD) treatment was associated with long-term seizure reduction in patients with various treatment-resistant epilepsies who participated in the CBD Expanded Access Program. A phase 3 trial showed CBD effectively treats tuberous sclerosis complex (TSC)-associated seizures, which are primarily of focal origin. However, the effectiveness of CBD in non-TSC focal epilepsies is not well reported. Here, we evaluate CBD treatment outcomes among patients with a variety of focal epilepsies, including Tsc. Methods: Patients received plant-derived highly purified CBD (Epidiolex; 100 mg/mL oral solution) doses starting at 2-10 mg/kg/day and titrated up to each patient's limit or to a maximum of 25-50 mg/kg/day. CBD effectiveness was assessed by the median percentage change from baseline in monthly frequency of focal and total seizures and by responder rates through 144 weeks of treatment. Safety data were reported for the full follow-up period. Results: Of 140 patients with focal epilepsies, 33 (24%) had TSC and 107 (76%) had other focal epilepsies, including cortical dysplasia (14%), frontal lobe epilepsy (10%), and malformation of cortical development (9%). Median age was 11.9 years (range = 2-31) in the TSC group and 17.8 years (range = 2-73) in the non-TSC group. Median CBD daily dose was comparable between TSC and non-TSC groups (25 and 23 mg/kg/day, respectively). CBD treatment was associated with a median reduction from baseline of 51%-87% in focal seizures and 44%-87% in total seizures in the TSC group and 46%-75% and 45%-71% in the non-TSC group, respectively. Responder rates were similar for both groups. Adverse events occurred in 91% of the TSC group and 96% of the non-TSC group. Significance: Open-label CBD treatment was associated with sustained seizure reduction through 144 weeks, with a consistent safety profile in patients with treatment-resistant focal epilepsies, regardless of epilepsy type.