In this 2nd interim analysis of an OLE trial (GWPCARE6/NCT02544763), we report safety (full follow-up) and efficacy (through 72 weeks) of add-on CBD for treatment of TSC-associated seizures.

Add-on CBD demonstrated efficacy with an acceptable safety profile in patients with TSC in the 16-week RCT.

Patients who completed the RCT received plant-derived highly purified CBD (Epidiolex^®, 100 mg/mL oral solution) in the OLE (titration to 25 mg/kg/day or up 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).

Of 201 RCT completers, 199 (99%) patients entered the OLE. Median (range) age: 10.7 (1.1–56.8) years. Baseline median seizure frequency/28 days: 57 seizures. At this analysis, 12% of patients completed treatment, 31% were withdrawn, and 57% were ongoing. OLE median (range) treatment time: 372 (18–1127) 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 AEs: diarrhea (45%), seizure (28%), decreased appetite (23%), pyrexia (21%), and vomiting (20%). ALT/AST >3×ULN occurred in 17 (9%) patients; 12 on concomitant valproate No patient met Hy’s law criteria. There was 1 death due to cardiopulmonary failure, deemed not treatment-related by the investigator. Median percentage reductions in TSC-associated seizures (12-week windows through 72 weeks): 53%–75%. Seizure reductions were 54%–80% for patients with a modal dose ≤25 mg/kg/day (n=145). ≥50%, ≥75%, and 100% responder rates were maintained up to 72 weeks, ranging from 52%–63%, 29%–51%, and 6%–19%, across 12-week windows. Improvement on S/CGIC was reported by 85% and 89% of subjects/caregivers at 26 and 52 weeks.

Add-on CBD treatment was well tolerated and produced sustained reductions in TSC-associated seizures for up to 72 weeks.

FUNDING: GW Research Ltd.