Long- term efficacy and safety of cannabidiol in patients with treatment- resistant epilepsies: Four- year results from the expanded access program

Objective: Cannabidiol (CBD) expanded access program, initiated in 2014, provided add -on CBD to patients with treatment-resistant epilepsies (TREs) at 35 US epilepsy centers. Prior publications reported results through December 2016; herein, we present efficacy and safety results through January 2019.Methods: Patients received plant-derived highly purified CBD (Epidiolex (R); 100 mg/ml oral solution), increasing from 2 to 10 mg/kg/day to tolerance or maximum 25- 50 mg/kg/day dose, depending on the study site. Efficacy endpoints included percentage change from baseline in median monthly convulsive and total seizure frequency and >= 50%, >= 75%, and 100% responder rates across 12 -week visit windows for up to 192 weeks. Adverse events (AEs) were documented at each visit.Results: Of 892 patients in the safety analysis set, 322 (36%) withdrew; lack of efficacy (19%) and AEs (7%) were the most commonly reported primary reasons for withdrawal. Median (range) age was 11.8 years (range = 0- 74.5), and patients were taking a median of three (range = 0- 10) antiseizure medications (ASMs) at baseline; the most common ASMs were clobazam (47%), levetiracetam (34%), and valproate (28%). Median top CBD dose was 25 mg/kg/day; median exposure duration was 694 days. Median percentage reduction from baseline ranged 50%- 67% for convulsive seizures and 46%- 66% for total seizures. Convulsive seizure responder rates (>_50%, >_75%, and 100% reduction) ranged 51%- 59%, 33%- 42%, and 11%- 17% of patients across visit windows, respectively. AEs were reported in 88% of patients and serious AEs in 41%; 8% withdrew because of an AE. There were 20 deaths during the study deemed unrelated to treatment by the investigator. The most common AEs (>_20% of patients) were diarrhea (33%), seizure (24%), and somnolence (23%).Significance: Add on CBD was associated with sustained seizure reduction up to 192 weeks with an acceptable safety profile and can be used for long term treatment of TREs.

Automated summary

The CBD expanded access program initiated in 2014 provided additional CBD treatment for patients with treatment-resistant epilepsies. The study showed that CBD treatment was effective in reducing seizure frequency and had an acceptable safety profile for long-term use in patients with treatment-resistant epilepsies.