Abstracts

Rationale: Initial data suggest that add-on CBD may be efficacious in patients with TRE. The long-term effectiveness and safety of add-on CBD in patients with TRE enrolled in an Expanded Access Program (EAP) and treated for >10 weeks between January 2014 and December 2016 were assessed. Methods: During the 4-week baseline period, parents/caregivers kept seizure diaries of all countable seizures. 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/day to tolerance or a maximum dose of 25–50 mg/kg/day, depending on the site (median dose: 25 mg/kg/day [IQR: 15-25] at 12 weeks; 25 mg/kg/day [IQR: 21-30] at 96 weeks). Patients were seen every 2–4 weeks during the first 12 weeks and at 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 all U.S. EAP patients with efficacy data (N=580), 136 (23%) withdrew during the study period; the top reasons were lack of efficacy for 87 (15%) and AEs for 25 (4%). Results are presented for patients on CBD >10 weeks: 542 patients comprise the safety set with median (Q1, Q3) treatment duration of 54 weeks (27, 100) and 523 patients comprise the efficacy set. Mean (min, max) age was 13.0 y (0.4, 62.1); 23% were ≥18 y. Median (Q1, Q3) number of concomitant antiepileptic drugs was 3 (2, 4). Baseline monthly median (Q1, Q3) seizure frequency was 40 (12, 112) for convulsive and 72 (22, 196) 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, the ≥50%, ≥75%, and 100% responder rates were also consistent across the five time points.Most common AEs in this subset of patients on CBD >10 weeks are summarized in Table 2. Abnormal liver AEs were reported in 11% of patients. All causality serious AEs were reported in 35% of patients; most common were convulsion (10%), status epilepticus (8%), and pneumonia (5%). Eight patients died, considered unrelated to treatment. In patients treated for <10 weeks and not included in this analysis, there were 4 deaths (including 1 prior to starting CBD), considered unrelated to treatment. Across the entire CBD development program, common adverse reactions are somnolence, decreased appetite, diarrhea, pyrexia, fatigue, lethargy,  rash, nasopharyngitis, and pneumonia.  Dose-related reversible elevation 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 TRE. Funding: Funded by GW Research Ltd.