Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698212
Poster Presentations
Poster Area GNP Epilepsy 1
Georg Thieme Verlag KG Stuttgart · New York

Long-term Safety and Efficacy of Add-on Cannabidiol (CBD) Treatment in Patients with Lennox-Gastaut Syndrome in an Open-label Extension Trial (GWPCARE5)

Anup Patel
1   Nationwide Children’s Hospital, Division of Child Neurology, Columbus, Ohio, United States
,
Antonio Gil-Nagel
2   Hospital Ruber International, Department of Neurology, Madrid, Spain
,
Richard Chin
3   Royal Hospital for Sick Children, Department of Paediatric Neurosciences, Edinburgh, United Kingdom
,
Wendy Mitchell
4   Children’s Hospital Los Angeles, Division of Neurology, Los Angeles, California, United States
,
M. Scott Perry
5   Cook Children’s Medical Center, Department of Neurosciences, Fort Worth, Texas, United States
,
Arie Weinstock
6   Oishei Children’s Hospital, Pediatric Neurology, Buffalo, New York, United States
,
Kevan VanLandingham
7   Greenwich Biosciences, Inc., Neurology, Carlsbad, California, United States
› Author Affiliations
Further Information

Publication History

Publication Date:
11 September 2019 (online)

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Research Question: Lennox-Gastaut syndrome (LGS) is a rare epileptic encephalopathy that is often treatment-resistant. CBD significantly reduced seizures with an acceptable safety profile in patients with LGS in 2 Phase 3 trials (GWPCARE3/NCT02224560; GWPCARE4/NCT02224690). A second interim analysis of the open label extension (OLE) of these 2 trials was conducted to assess long-term safety and efficacy of add-on CBD in patients with LGS.

Materials and Methods: Patients who completed a 14-week, double-blind, randomised controlled trial (GWPCARE3; GWPCARE4) could enter this OLE trial, GWPCARE5 (NCT02224573). Patients received GW Pharmaceuticals’ formulation of plant-derived highly purified CBD in oral solution (100 mg/mL) for ≤3 years. Primary endpoint was safety. Secondary endpoints were drop and total seizure frequency, and Subject/Caregiver Global Impression of Change (S/CGIC).

Results: 99% (366/368) of eligible patients with LGS entered the OLE trial. Median follow-up was 61 weeks (3 days to 87 weeks); 88 patients (24%) withdrew. Mean age: 16 years; 33% ≥18 years; 54% male. Baseline median seizure frequency per 28 days: 80 drop seizures; 168 total seizures. During the extended follow-up, treatment-emergent adverse event (AE) incidence: 94%; serious AE incidence: 33%; 11% discontinued owing to AEs. Most common AEs (≥20%): diarrhoea, convulsion, somnolence, pyrexia, vomiting and decreased appetite. Forty-seven patients (13%) had elevations in liver transaminases >3× upper limit of normal; 35 (74%) were taking concomitant valproate. There were 5 deaths; none deemed treatment-related by the investigator. Median percentage reductions in seizure frequency (12-week windows over 72 weeks): 48%–70% for drop seizures; 48%–63% for total seizures. Approximately 88% of patients/caregivers reported an improvement in overall condition on the S/CGIC at Weeks 24 and 48.

Discussion and Conclusion: Long-term add-on CBD treatment had a similar AE profile to that observed in the core studies at 14 weeks. Reductions in drop and total seizure frequency and improvements in overall condition were maintained through 72 weeks.

Funding: GW Research Ltd, Cambridge, UK.