Evaluate the effect of CBD on convulsive (clonic, tonic, tonic-clonic, atonic, focal to bilateral tonic-clonic) and nonconvulsive (focal, absence, myoclonic, myoclonic-absence, spasms) seizures and safety in patients with TREs in the EAP.

The EAP provided open-label CBD to patients with TREs at 35 US epilepsy centers (2014–2019).

Patients received add-on CBD (Epidiolex®; 100 mg/mL oral solution) increasing from 2–10 mg/kg/d to tolerance or maximum 25–50 mg/kg/d dose. Efficacy endpoint: percentage change from baseline in median monthly frequency of convulsive and nonconvulsive seizures (24-wk treatment windows through 144 wks). Safety for up to 256 wks.

Of 892 patients with safety data, 322 (36%) withdrew; most common reasons: lack of efficacy (19%) and AEs (7%). Median (range) age: 11.8 yrs (0.4–74.5); median (range) baseline ASDs: 3 (0–10). Most common baseline ASDs: clobazam (48%), levetiracetam (34%), valproate (28%). Median (Q1, Q3) top CBD dose: 25 mg/kg/d (24, 30); median (range) exposure duration: 694 days (10–1793). For efficacy set (n=840), baseline median (Q1, Q3) monthly convulsive seizure frequency: 40 (12, 112); nonconvulsive seizure frequency: 38 (9, 140). CBD produced 47%–100% reduction from baseline in convulsive and 50%–100% reduction in nonconvulsive seizures. ≥50% responder rates: 49%–78% of patients for convulsive and 50%–92% for nonconvulsive seizures. AEs were reported by 88% of patients and serious AEs by 41%. There were 20 deaths, deemed unrelated to treatment by the investigator. Most common AEs (≥20% of patients): diarrhea (33%), convulsion (24%), somnolence (23%). ALT elevations >5×ULN occurred in 25/829 (3%) patients with baseline and on-treatment ALT measurements; 18 patients were on valproate. No patient met Hy’s Law criteria for severe drug-induced liver injury.

Add-on CBD produced sustained reduction in convulsive and nonconvulsive seizure types for up to 144 wks and was well tolerated.

Funding: GW Research Ltd.