Cannabidiol (CBD) significantly reduces drop seizure frequency in Lennox-Gastaut syndrome (LGS): results of a multi-center, randomized, double-blind, placebo controlled trial (GWPCARE4) (S21.001)

Objective: Evaluate efficacy of CBD added to antiepileptic drug (AED) therapy for the treatment of seizures associated with LGS. Background: Multiple data streams suggest that CBD may be an effective antiepileptic treatment; however, class 1 evidence supporting its use is lacking. Here we present the first controlled trial of CBD in LGS. Design/Methods: Eligible patients were 2–55 years old and had a clinical diagnosis of LGS, ≥2 drop seizures each week during baseline, and documented failures on ≥1 AED. Patients were randomized (1:1) to receive 20 mg/kg/day CBD (oral solution) or matched placebo, for 14 weeks (2-week titration; 12-week dose maintenance). The primary efficacy endpoint was percentage change from baseline in drop seizure frequency (tonic, atonic, and tonic-clonic) over the entire 14-week treatment period for patients on CBD vs placebo. Results: 171 patients were randomized (86 CBD; 85 placebo); 14 CBD and 1 placebo patient withdrew early. Demographic and baseline characteristics were evenly distributed between groups; mean age was 15 years (34% of patients ≥18 years) and median drop seizure frequency was 74/month. Patients had previously taken a median of 6 AEDs, and were taking a median of 3 concomitant AEDs throughout the trial. CBD resulted in a significantly greater median percent reduction in monthly drop seizure frequency, versus placebo (44% vs. 22%; p=0.0135). The treatment difference was established during the first 4 weeks of the maintenance period. 86% of CBD and 69% of placebo patients had adverse events (AEs); the most common were diarrhea, somnolence, pyrexia, decreased appetite, and vomiting. Treatment-related serious AEs were reported in 9 CBD patients and 1 placebo patient. There was 1 death (CBD), considered unrelated to treatment. Conclusions: Results from this trial suggest that CBD add-on therapy for the treatment of drop seizures associated with LGS may be efficacious and generally well-tolerated. (NCT02224690) Study Supported by: GW Research, Ltd Disclosure: Dr. French has received personal compensation for activities with Acorda, Adamas, Alexza, Anavex, Biogen, BioPharm Solutions, Cerecor, Concert Pharmaceuticals, Convance, Eisai, Georgia Regents University, GSK, GW Pharma, Marinus, MonosolRx, Monteris, Nestle-Health Science, Neurelis, Novartis, Ovid Therapeutics Inc., Pfizer, Pfizer-Neusentis, Pronutria, Roivant, Sage, SK Life Sciences, Sunovion, Supernus, Takeda, UCB Inc., Upsher Smith, Xenon Pharmaceuticals, Zogenix, Zynerba as a consultant. Dr. Thiele has received personal compensation for activities with GW Pharma, Zogenix, Eisai Pharmaceuticals, Dravet, Lennox Gastaut and TSC as a consultant or PI. Dr. Thiele has received research support from GW Pharma and Zogenix. Dr. Mazurkiewicz-Beldzin has received personal compensation for activities with UCB and TEVA Pharmaceuticals as an advisory board member. Dr. Benbadis has received personal compensation for activities with Cyberonics, Eisai, Inc., Lundbeck, Sunovion and UCB Pharma. Dr. Benbadis has received personal compensation in an editorial capacity for eMedicine, WebMD, Medscape, and Up-To-Date. Dr. Marsh has received personal compensation for activities with GLC Consultants and SBSE. Dr. Marsh has received research support from GW Pharma and Neuren Pharmacuticals. Dr. Joshi has nothing to disclose. Dr. Roberts has received personal compensation for activities with GW Pharma as an employee. Dr. Taylor has nothing to disclose. Dr. Sommerville has received personal compensation for activities with King Pharmaceuticals as an employee. Dr. Sommerville holds stock and/or stock options in GW, Abbott, Abbvie, Johnson and Johnson, Mylan, and Merck.