To report the effect of CBD in EAP patients with focal-onset seizures, including focal aware seizures (FAS), focal impaired awareness seizures (FIAS), and focal to bilateral tonic-clonic seizures (FBTCS).

Four-year EAP results demonstrated that CBD was associated with sustained seizure improvement in TRE.

Patients received plant-derived highly purified CBD (Epidiolex^®; 100 mg/mL oral solution) starting at 2–10 mg/kg/d and further titrated to a maximum of 25–50 mg/kg/d. Percentage change from baseline in median monthly frequency of focal seizures and responder rates (RRs) across 12-week intervals through 144 treatment weeks were evaluated.

Of 892 EAP patients, 351 (39%) experienced focal seizures. Mean (range) age: 15.8 (<1–73.2) years. Median (range) ASMs at baseline: 3 (0–10). Most common ASMs: clobazam (43%), levetiracetam (35%). Patients withdrew mainly because of lack of efficacy (18%) or AEs (5%). Median CBD exposure: 684 days (range, 10–1793). Median top CBD dose: 25 mg/kg/d (IQR, 24–31). Baseline median (IQR) monthly seizure frequency: 28 (4–87) for FAS, 22 (7–76) for FIAS, and 12 (4–41) for FBTCS. CBD treatment was associated with median reduction of 67%–99% (FAS), 61%–78% (FIAS), and 50%–81% (FBTCS). The FAS RRs were 61%–88% (≥50% reduction), 45%–72% (≥75% reduction), and 20%–46% (100% reduction). The FIAS RRs were 55%–69%, 41%–56%, and 18%–29%, respectively. The FBTCS RRs were 52%–69%, 41%–54%, and 23%–36%, respectively. Among patients with any focal seizure, 90% reported AEs and 38% serious AEs; 7% withdrew due to AEs. Five deaths, not considered treatment-related, occurred in the cohort. Most common AEs: diarrhea (40%), convulsion (24%), somnolence (21%). Liver-related AEs (>1%) were increased ALT and AST (4% each) and abnormal liver function test (3%).