Abstract
Objective: 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.
Background: 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.
Design/Methods: 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.
Results: 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.
Conclusions: CBD produced consistent reductions in TSC-associated seizures in patients with and without IS history.
FUNDING: GW Research Ltd.
Disclosure: Dr. Saneto has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for REATA. Dr. Saneto has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GW Pharmaceuticals. The institution of Dr. Saneto has received research support from NIH. The institution of Dr. Saneto has received research support from Zogenix. The institution of Dr. Saneto has received research support from GW Pharmaceuticals. Dr. Sparagana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Biosciences. Dr. Sparagana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nobelpharma. The institution of Dr. Sparagana has received research support from Greenwich Biosciences. The institution of Dr. Sparagana has received research support from Tuberous Sclerosis Alliance. The institution of Dr. Sparagana has received research support from Novartis. Dr. Sparagana has a non-compensated relationship as a Professional Advisory Board Member, committee member with Tuberous Sclerosis Alliance that is relevant to AAN interests or activities. Patrick KL Kwan, MD,PhD has nothing to disclose. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aquestive. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for LivaNova. Dr. Wheless has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Supernus. Dr. Wheless has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Greenwich. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BioMarin. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zogenix. Kerry Hyland has received personal compensation for serving as an employee of GW Pharmaceuticals. Kerry Hyland has received stock or an ownership interest from GW Pharmaceuticals. Dr. Sahebkar-Moghaddam has received personal compensation for serving as an employee of gw. Dr. Sahebkar-Moghaddam has received stock or an ownership interest from GW.
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