Abstract Details

Title Long-term Safety and Efficacy of Cannabidiol (CBD) for the Treatment of Seizures in Patients with Tuberous Sclerosis Complex (TSC) in an Open-label Extension (OLE) Trial (GWPCARE6)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S31 - Epilepsy/Clinical Neurophysiology (EEG) 3 (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Objective To evaluate the long-term safety and efficacy of CBD as adjunctive treatment of seizures in patients with TSC; an interim analysis of the OLE of the phase 3 randomized controlled trial (RCT) GWPCARE6 (NCT02544750).

Background A 16-week, double-blind RCT demonstrated the efficacy of CBD, with an acceptable safety profile, for treatment of seizures in patients with TSC.

Design/Methods Patients who participated in the RCT could enroll to receive a plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) in the OLE (starting dose 25 mg/kg/day with titration up to 50 mg/kg/day). Primary endpoint: safety. Secondary endpoints: percentage reduction in seizures (countable focal or generalized), responder rates, and Subject/Caregiver Global Impression of Change (S/CGIC).

Results

Of 201 patients who completed the RCT, 199 patients (99%) entered the OLE. Mean age: 13 years (range, 1-57); 59% male. Baseline median seizure frequency/28 days: 57 seizures. OLE median treatment time: 267 days (range, 18-910). Mean modal dose: 27 mg/kg/day; 39 patients (20%) withdrew. Adverse event (AE) incidence was 93%; serious AE incidence: 15%; 6% discontinued due to AEs. There was 1 death deemed unrelated to treatment by the investigator. Most common AEs (≥20%): diarrhea (42%), seizure (22%), decreased appetite (20%). Elevated ALT/AST >3× ULN were reported in 17 (8.5%) patients; 12 were on concomitant valproate. Median percentage reductions in seizure frequency (12-week windows over 48 weeks) were 54-68%. Seizure responder rates (≥50%, ≥75%, and 100% reduction) were maintained up to 48 weeks, ranging from 53-61%, 29-45%, and 6-11% across 12-week visit windows. Improvement in S/CGIC was reported by 87% of patients/caregivers at week 26, with 53% reporting much/very much improvement.

Conclusions Long-term adjunctive CBD treatment was well tolerated in patients with TSC, with an AE profile similar to that observed previously. Reductions in seizures were maintained through 48 weeks with a high proportion of patients reporting global improvement.

Authors/Disclosures
Elizabeth Thiele, MD (Massachusetts General Hospital) PRESENTER	Dr. Thiele has received personal compensation in the range of $10,000-$49,999 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. An immediate family member of Dr. Thiele has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Thor labs. 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 takeda. 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 $500-$4,999 for serving as a Consultant for Azurity. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 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.
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.
Francis M. Filloux, MD (Pediatric Neurology)	Dr. Filloux has nothing to disclose.
Patrick K. Kwan, MD, PhD (United Christian Hospital)	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.
Steven P. Sparagana, MD, FAAN	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.
James W. Wheless, MD, FAAP, FAAN (UTHSC-Pediatric Neurology)	Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. 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 as a Consultant for Azurity. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LivaNova. 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 Jazz. 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. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelius.

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