In this post hoc analysis of a phase 3 randomized controlled trial (RCT: GWPCARE6/NCT02544763), we compared response to add-on CBD in patients with TSC and treatment-resistant epilepsy with and without IS history.

Approximately 30%–60% of patients with TSC have a history of IS and are more likely to have treatment-resistant epilepsy than those without IS. CBD was significantly superior to placebo in reducing seizures in patients with TSC in the phase 3 RCT.

Patients received plant-derived highly purified CBD (Epidiolex^®, 100 mg/mL oral solution) titrated to 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks. Negative binomial regression effect modification analysis was used to assess whether IS history affected CBD efficacy.

138/224 (62%) patients had IS history. Median (range) age: 12.2 years (1.1–56.8) and 10.5 years (1.6–55.8) for patients with and without IS history. Median (Q1, Q3) baseline monthly TSC-associated seizure frequency: 59 (28, 117) and 51 (29, 96) for patients with and without IS history. CBD reduced TSC-associated seizures vs placebo regardless of IS history (interaction p-value: 0.803 for CBD25, 0.561 for CBD50). Percentage reduction in seizures: for patients with IS history: 45% for CBD25, 43% for CBD50, and 23% for placebo; for patients without IS history:: 54% for CBD25, 55% for CBD50, and 32% for placebo. AE incidence: 93% for CBD25, 100% for CBD50, and 95% for placebo. 8 patients (11%) on CBD25, 10 (14%) on CBD50, and 2 (3%) on placebo discontinued treatment due to AE(s). Most common AEs: diarrhea and somnolence, occurring more frequently with CBD than placebo. ALT/AST elevations (>3×ULN): 9 (12%) patients on CBD25, 19 (26%) on CBD50, none on placebo; 79% were on concomitant valproate.

CBD produced consistent reductions in TSC-associated seizures in patients with and without IS history.

FUNDING: GW Research Ltd.