Long-Term Safety and Efficacy of Cannabidiol (CBD) Treatment in Patients with Dravet Syndrome (DS): 3-Year Interim Results of an Open-Label Extension (OLE) Trial (GWPCARE5) (439)

Objective: Assess the long-term safety and efficacy of add-on CBD treatment in patients with Dravet syndrome (DS) in the third analysis of the open-label extension (OLE; GWPCARE5 [NCT0224573]) of two randomized controlled trials (RCTs), GWPCARE1 (Phase 2/3) and GWPCARE2 (Phase 3).

Background: DS is a developmental and epileptic encephalopathy that is often treatment-resistant, with onset by 15 months and a high mortality rate.

Design/Methods: Patients initially received 20 mg/kg/day plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution); the dose could be decreased or increased to 30 mg/kg/day at the investigator’s discretion. Primary endpoint: safety. Secondary efficacy endpoints: median percentage change from baseline in convulsive and total seizure frequency.

Results: Of 330 patients who completed RCTs, 315 enrolled in GWPCARE5. At data cut-off, the OLE was ongoing and 43% of patients had withdrawn. Mean patient age was 10 years; 97% <18 years. Patients were taking a median of 3 concurrent antiepileptic drugs at baseline; during the OLE, 68% were taking clobazam, 67% valproate, and 38% stiripentol. Mean modal CBD dose was 22 mg/kg/day. Adverse events (AEs) and serious AEs occurred in 97% and 41% patients, respectively; 9% discontinued due to AEs. AEs of increased aspartate aminotransferase occurred in 12% of patients. Four deaths occurred (considered nontreatment-related by the investigator). Median percentage reductions in seizure frequency overall (12–week windows over 156 weeks) was 45%–73% for convulsive and 49%–80% for total seizures.

Conclusions: Long-term treatment with add-on CBD in patients with DS produced sustained seizure reductions, with no new safety concerns.

Disclosure: Dr. Halford has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Brain Sentinel. Dr. Halford has received research support from Brain Sentinel.Dr. Scheffer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with scientific advisory boards for BioMarin, Nutricia, GSK, Xenon Pharmaceuticals, UCB, received speaker honoraria, support for travel from BioMarin, UCB, GSK, Eisai. Dr. Scheffer has received royalty, license fees, or contractual rights payments from Royalty payment received for PCT/AU2012/001321. Dr. Scheffer has received research support from Trial investigator for GW Pharma, Zogenix, UCB, Ultragenyx, Ovid Therapeutics, Zynerba.Dr. Nabbout has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultant/advisor, Eisai, GW Pharma, Novartis, Shire, Zogenix; Speaker, Advicenne, BioMarin, GW Pharma, Novartis, Zogenix. Dr. Nabbout has received research support from Eisai, GW Pharma, UCB, Zogenix. Dr. Sanchez-Carpintero has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with scientific advisory boards of GW Pharma, Zogenix and Novartris; speaker’s bureau GWPharma. Dr. Sanchez-Carpintero has received research support from principal investigator for GW Pharma, Zogenix and Takaeda initiated trials. Dr. Shiloh-Malawsky has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Checketts has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GW Research, Ltd. Dr. Checketts holds stock and/or stock options in GW Research, Ltd.Dr. Dunayevich has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences, Inc. Dr. Dunayevich has received compensation for serving on the Board of Directors of GW Pharmaceuticals plc. Dr. Dunayevich holds stock and/or stock options in Stock in GW Pharmaceuticals plc.