Abstracts

Rationale: Add-on CBD has demonstrated efficacy against seizures associated with TSC with an acceptable safety profile in a randomized, placebo-controlled phase 3 trial (GWPCARE6; NCT02544763). In this post hoc analysis of GWPCARE6, we evaluated reduction in seizure frequency as cumulative distribution function (CDF) to determine the proportion of patients with TSC, treated with CBD or placebo, who reached all continuous responder rate thresholds and the longest seizure-free intervals.

Methods: Eligible patients (1–65 yrs) with treatment-resistant epilepsy who had ≥8 TSC-associated (countable focal and generalized) seizures during the 4-wk baseline period and were taking ≥1 antiseizure medication (ASM) at baseline were randomized to receive plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) at 25 mg/kg/d (CBD25) or 50 mg/kg/d or matched placebo for 16 wks. In this analysis, efficacy of CBD25 vs placebo was evaluated by percent reduction from baseline in TSC-associated seizure frequency and presented as CDF, and longest seizure-free intervals.

Results: This post hoc analysis included 75 patients who received CBD25 and 76 who received placebo. The median (range) age was 11 (1–57) yrs. Patients had previously tried and discontinued a median of 4 ASMs and were currently taking a median of 3 ASMs. In the 4-wk baseline period, the median (Q1, Q3) TSC-associated seizure frequency was 56 (21, 101) for CBD25 and 54 (26, 102) for placebo, and the mean (standard deviation [SD]) longest seizure-free interval was 3 (3) days for CBD25 and 2 (2) days for placebo. CBD produced a significantly greater reduction in TSC-associated seizures vs placebo (treatment ratio [95% CI], 0.699 [0.567–0.861]; P=0.0009). A greater proportion of patients on CBD25 vs placebo achieved all continuous responder rate thresholds for TSC-associated seizures; response rates for ≥25%, ≥50%, and ≥75% reduction were 68%, 44%, and 19% for CBD25 vs 43%, 22%, and 0% for placebo. Patients on CBD were seizure free for longer intervals than those on placebo, with mean (SD) longest seizure-free intervals of 11 (17) days for CBD25 and 6 (6) days for placebo. More patients taking CBD25 had 7-, 14-, 21-, and 28-day seizure-free intervals than placebo (45% vs 33%, 24% vs 14%, 12% vs 0%, and 8% vs 0%). AEs were reported by 93% of patients on CBD25 and 95% on placebo; 8 patients (11%) on CBD25 and 2 (3%) on placebo discontinued treatment because of an AE. The most common AEs were diarrhea and decreased appetite, occurring more frequently with CBD than placebo. ALT/AST elevations ( >3× ULN) occurred in 9 (12%) patients on CBD25 and none on placebo; 78% of these patients were on concomitant valproate.

Conclusions: As previously reported for the RCT, CBD was significantly superior to placebo in reducing TSC-associated seizures. The post hoc analyses showed longer seizure-free intervals with CBD than placebo in patients with treatment-resistant epilepsy associated with TSC.

Funding: Please list any funding that was received in support of this abstract.: GW Research Ltd.