Abstracts

Rationale: Recent phase 3 data demonstrate that add-on cannabidiol (CBD) may be efficacious for patients with treatment-resistant epilepsies (TRE), including Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in a 14-week treatment trial. Here, we present long term pooled results from an Expanded Access Program (EAP) to provide CBD to patients with TRE, focused on the subset of patients with DS/LGS treated for >10 weeks between January 2014 and December 2016. Methods: During the 4-week baseline period, parents/caregivers kept seizure diaries of all countable seizure types. Patients received a plant-derived pharmaceutical formulation of CBD (100 mg/mL) in oral (sesame oil) solution (Epidiolex: GW Pharmaceuticals) at a gradually increasing dose from 2–10 mg/kg/d to tolerance or a maximum dose of 25–50 mg/kg/d, depending on site (median dose: 21 mg/kg/d [IQR: 15-25] at 12 weeks; 25 mg/kg/d [IQR: 21-25] at 96 weeks). Patients were seen every 2–4 weeks during the first 12 weeks and at regular 3-6-month intervals thereafter. Efficacy endpoints were percentage change from baseline in convulsive and total seizures and ≥25%, ≥50%, and ≥100% responder rates. Adverse events (AEs) were recorded. Results: Of the 580 U.S. EAP participants with efficacy data, 147 (25%) had DS/LGS diagnoses. Forty (27%) withdrew during the study period; primary reason was reported as AE for 4 (3%) and lack of efficacy for 30 (20%) patients. Of patients with >10 weeks of treatment: 134 patients comprise the safety set with mean (SD) treatment duration of 77 (40) weeks and 130 patients comprise the efficacy set. Mean (min, max) age was 12.5 y (1.7, 51.0), with 20% aged ≥18 y. Median (Q1, Q3) number of concomitant antiepileptic drugs was 3 (2, 4). Monthly median (Q1, Q3) seizure frequency at baseline was 38 (16, 98) for convulsive and 62 (24, 140) for total seizures. Median percentage changes in convulsive and total seizures were consistent at Weeks 12, 24, 48, 72, and 96 (Table 1). For both convulsive and total seizures, ≥50%, ≥75%, and 100% responder rates were consistent across the five time points. Most common AEs in this subset of patients who remained on CBD >10 weeks are summarized in Table 2. Abnormal liver AEs were reported in 16% of patients. All causality serious AEs were reported in 45% of patients; most common were convulsion (16%), status epilepticus (10%), pneumonia (5%), and pyrexia (5%). There were no deaths. Across the entire CBD development program, common adverse reactions are somnolence, decreased appetite, diarrhea, pyrexia, fatigue, lethargy, rash, nasopharyngitis, and pneumonia.  Dose-related reversible elevations of liver transaminases without elevation of bilirubin is an identified adverse reaction of special interest for CBD. Conclusions: The EAP is an ongoing study reflective of real-world clinical practice. To date, CBD has been generally well tolerated. This study supports previous observational and randomized controlled trial data showing add-on CBD may be an efficacious long-term treatment option for LGS and DS in children and adults.  Funding: Funded by GW Research Ltd