Abstract Details

Title Effect of Add-on Cannabidiol (CBD) on Seizure Frequency and Seizure-Free Intervals in Patients With Seizures Associated With Tuberous Sclerosis Complex (TSC): Phase 3 Trial GWPCARE6 Post Hoc Analysis

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-005

Objective Post hoc analysis 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.

Background Add-on CBD demonstrated efficacy against seizures associated with TSC with an acceptable safety profile in phase 3 trial GWPCARE6 (NCT02544763).

Design/Methods Patients received 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 weeks. Efficacy of CBD25 (n=75) vs placebo (n=76) was evaluated by percent reduction from baseline in TSC-associated seizures and longest seizure-free intervals.

Results Median (range) age: 11 (1–57) years. Median (Q1, Q3) TSC-associated seizure frequency during 4-wk baseline: 56 (21, 101) for CBD25 and 54 (26, 102) for placebo. Mean (standard deviation [SD]) longest seizure-free interval during 4-wk baseline: 3 (3) days for CBD25 and 2 (2) days for placebo. CBD produced significantly greater reduction in TSC-associated seizures than placebo (treatment ratio [95% CI], 0.699 [0.567–0.861]; P=0.0009). Patients with ≥25%, ≥50%, and ≥75% reduction: 68%, 44%, and 19% for CBD25 and 43%, 22%, and 0% for placebo. Mean (SD) longest seizure-free intervals: 11 (17) days for CBD25 and 6 (6) days for placebo; patients with 7-, 14-, 21-, and 28-day seizure-free intervals for CBD25 vs placebo: 45% vs 33%, 24% vs 14%, 12% vs 0%, and 8% vs 0%. AE incidence: 93% of patients taking CBD25 and 95% taking placebo; 11% taking CBD25 and 3% taking placebo discontinued treatment because of an AE. Most common AEs: 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% were on concomitant valproate.

Conclusions CBD was superior to placebo in reducing seizures and producing longer seizure-free intervals in patients with TSC-associated seizures.

Authors/Disclosures
Steven P. Sparagana, MD, FAAN PRESENTER	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.
Elizabeth Thiele, MD (Massachusetts General Hospital)	Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Pharma/Jazz. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for zogenix/UCB. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for nobelpharma. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for livanova. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Noema Pharma. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for pyros pharmaceutical/upsher smith. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus Pharmaceuticals. The institution of Dr. Thiele has received research support from GW Pharma/Jazz. The institution of Dr. Thiele has received research support from Zogenix/UCB. The institution of Dr. Thiele has received research support from Stoke Therapeutics. The institution of Dr. Thiele has received research support from Biocodex. Dr. Thiele has received publishing royalties from a publication relating to health care.
E M. Bebin, MD, FAAN (UAB Epilepsy Center)	Dr. Bebin has received personal compensation for serving as an employee of Springworks Therapeutics. Dr. Bebin has received personal compensation for serving as an employee of Apertura Gene Therapy. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springworks Therapeutics. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Apertura. The institution of Dr. Bebin has received research support from NINDS. The institution of Dr. Bebin has received research support from FDA Orphan Drug Program.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Farhad Sahebkar-Moghaddam, MD (Amgen)	Dr. Sahebkar-Moghaddam has received personal compensation for serving as an employee of Jazz pharmaceuticals. Dr. Sahebkar-Moghaddam has stock in Jazz pharmaceuticals.

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