Long-Term Safety, Efficacy of Add-on Cannabidiol (CBD) for Treatment of Tuberous Sclerosis Complex-Associated Seizures in an Open-Label Extension

Background/Purpose: Interim analysis of an open-label extension (OLE) of a randomized controlled-trial (RCT) (GWPCARE6/NCT02544750) to evaluate long-term safety and efficacy of add-on cannabidiol (CBD) for tuberous sclerosis complex (TSC)-associated seizures.

Methods: Patients who completed the RCT received plant-derived highly purified CBD medicine (Epidyolex, 100 mg/mL oral solution; starting dose 25 mg/kg/day, titrated to ≤50 mg/kg/day). Primary endpoint: safety. Secondary endpoints: percentage change in TSC-associated seizures (countable focal or generalized), responder rates, and Subject/Caregiver Global Impression of Change (S/CGIC).

Results: Of 201 RCT completers, 199 (99%) entered OLE. Median (range) age: 10.7 (1.1–56.8) years. Baseline median TSC-associated seizure frequency/28 days: 57 seizures. At this analysis, 12% of patients completed treatment, 31% were withdrawn. OLE median (range) treatment time: 372 (18–1,127) days. Mean (SD) modal dose: 28 (9) mg/kg/day. AE incidence: 94%; serious AE incidence: 26%; 8% discontinued due to AE(s). Most common AE: diarrhea (45%). ALT/AST >3 × ULN occurred in 17 patients (9%); 12 on concomitant valproate. No patient met Hy's law criteria. One death occurred due to cardiopulmonary failure, deemed not treatment-related by investigator. Median percentage reductions in seizures (12-week windows through 72 weeks): 53–75%. Seizure responder rates (≥50%, ≥75%, and 100%) ranged from 52 to 63%, 29 to 51%, and 6 to 19% across 12-week windows through 72 weeks. S/CGIC improvement was reported by 85 and 89% of subjects/caregivers at 26 and 52 weeks.

Conclusion: Add-on CBD was well tolerated and produced sustained TSC-associated seizure reductions for ≤72 weeks.

Funding

GW Research Ltd.

Publication History

Article published online:
28 October 2021