Post hoc analysis to evaluate CBD effectiveness against focal seizure subtypes (focal aware seizures [FAS], focal impaired awareness seizures [FIAS], and focal to bilateral tonic-clonic seizures [FBTCS]) in the GWPCARE6 OLE.

Add-on CBD reduced TSC-associated seizures (focal and generalized) in the randomized controlled trial (RCT) GWPCARE6 (NCT02544763) and its OLE (NCT02544750).

Patients received plant-derived highly purified CBD (Epidiolex^®; 100 mg/mL oral solution) at 25 or 50 mg/kg/d or placebo in the RCT, which included a 4-week titration and 12-week maintenance period. In OLE, all patients received CBD (maximum dose up to 50 mg/kg/d). Percentage change from baseline in the 28-day monthly average and responder rates (RRs) of focal seizure frequency across 12-week intervals through 144 treatment weeks were evaluated.

Of 224 randomized patients in GWPCARE6, 199 (89%) entered OLE; of these,168 (84%) reported focal seizures and 89 (45%) generalized seizures. In the focal seizure cohort, median age was 10.2 years (range, 1–56 years); median number of concomitant antiseizure medications (ASMs) was 4 (range, 0–15). Most commonly used ASMs included valproate (40%) and vigabatrin (35%). Median duration of CBD exposure was 596 days (range, 18–1462); median modal dose was 25 mg/kg/d (range, 5–50). CBD treatment was associated with median reductions of 54%–88% (overall focal seizures), 56%–84% (FAS), 54%–92% (FIAS), and 52%–74% (FBTCS) across 12-week intervals through 144 weeks. RRs for overall focal seizures (≥50%, ≥75%, and 100% reduction) throughout OLE were 54%, 33%, and 2%, respectively. RRs for focal seizure subtypes were consistent with overall focal seizure RRs. Treatment-emergent adverse event (TEAE) incidence in OLE was 96%. Most common TEAEs (>20%) were diarrhea, seizures, pyrexia, decreased appetite, and vomiting.

There was a robust effect of CBD across all focal seizure subtypes in patients with TSC. The safety profile was consistent with previous studies.