(123) Efficacy and Safety of Cannabidiol (CBD) in Patients with Treatment-Resistant Epilepsies (TREs) in the Expanded Access Program (EAP): Additional Efficacy Data for Convulsive and Nonconvulsive Seizure Subtypes

Rationale: The CBD EAP was initiated in 2014 to provide CBD to patients with TREs across 25 centers in the United States. Previous EAP publications have shown that add-on CBD produced a sustained reduction in convulsive seizures through 96 wks of treatment with an acceptable safety profile. Here we present additional efficacy data for convulsive (clonic, tonic, tonic-clonic, atonic, focal to bilateral tonic-clonic) and nonconvulsive (focal, absence, myoclonic, myoclonic-absence, spasms) seizure subtypes.

Methods: Patients received open-label plant-derived highly purified CBD (Epidiolex^®; 100 mg/mL oral solution) increasing from 2–10 mg/kg/d to tolerance or maximum 25–50 mg/kg/d dose, depending on the study site and institutional review board approval. Efficacy data were reported as the percent change from baseline in median monthly seizure frequency for each of the convulsive and nonconvulsive seizure subtypes through 144 wks of treatment. Safety data were reported over the full duration of follow-up (up to 256 wks).

Results: Of 892 patients with safety data, 322 (36%) withdrew during the study period; most common reasons were lack of efficacy (19%) and adverse events (AEs; 7%). At baseline, median (range) age was 11.8 yrs (0.4–74.5), and patients were taking a median (range) of 3 (0–10) antiseizure drugs (ASDs); most common baseline ASDs were clobazam (48%), levetiracetam (34%), and valproate (28%). Median top (Q1, Q3) CBD dose was 25 mg/kg/d (24, 30), and the median (range) exposure duration was 694 days (10–1793). For patients in the efficacy analysis set (n=840), the median (Q1, Q3) monthly seizure frequency at baseline was 40 (12, 112) for convulsive seizures and 71 (21, 200) for total seizures. CBD treatment produced 47%–100% reduction from baseline in convulsive and 50%–100% reduction in nonconvulsive seizure subtypes during 24-wk visit windows through 144 wks of treatment (Figure). At least 50% reduction was reported in 49%–78% of patients for convulsive seizure subtypes and 50%–92% of patients for nonconvulsive seizure subtypes during 24-wk visit windows through 144 wks. AEs were reported by 88% of patients and serious AEs by 41%; 8% of patients discontinued treatment due to an AE. There were 20 deaths during the study, all deemed unrelated to treatment by the investigator. Most common AEs (≥20% of patients) were diarrhea (33%), convulsion (24%), and somnolence (23%). Increases in alanine aminotransferase (ALT) >5× upper limit of normal occurred in 25 of 829 patients with baseline and on-treatment ALT measurements; 18 of these patients were on concomitant valproate. No patient met Hy’s Law criteria for drug-induced liver injury.

Conclusions: Add-on CBD produced sustained reduction in convulsive and nonconvulsive seizure subtypes for up to 144 wks with an acceptable safety profile. These results support the long-term use of CBD for patients with TREs with a variety of convulsive and nonconvulsive seizure subtypes.

Funding: Please list any funding that was received in support of this abstract.: GW Research Ltd.