Long-term Safety and Efficacy of Add-on Cannabidiol (CBD) for Treatment of Seizures Associated with Tuberous Sclerosis Complex (TSC) in an Open-Label Extension (OLE) Trial (GWPCARE6) (1127)

Objective: In this 2nd interim analysis of an OLE trial (GWPCARE6/NCT02544763), we report safety (full follow-up) and efficacy (through 72 weeks) of add-on CBD for treatment of TSC-associated seizures. Background: Add-on CBD demonstrated efficacy with an acceptable safety profile in patients with TSC in the 16-week RCT. Design/Methods: Patients who completed the RCT received plant-derived highly purified CBD (Epidiolex®, 100 mg/mL oral solution) in the OLE (titration to 25 mg/kg/day or up to 50 mg/kg/day). Primary endpoint: safety. Secondary endpoints: percentage change in TSC-associated seizures (countable focal or generalized), responder rates, and Subject/Caregiver Global Impression of Change (S/CGIC). Results: Of 201 RCT completers, 199 (99%) patients entered the OLE. Median (range) age: 10.7 (1.1–56.8) years. Baseline median seizure frequency/28 days: 57 seizures. At this analysis, 12% of patients completed treatment, 31% were withdrawn, and 57% were ongoing. OLE median (range) treatment time: 372 (18–1127) days. Mean (SD) modal dose: 28 (9) mg/kg/day. AE incidence: 94%; serious AE incidence: 26%; 8% discontinued due to AE(s). Most common AEs: diarrhea (45%), seizure (28%), decreased appetite (23%), pyrexia (21%), and vomiting (20%). ALT/AST >3×ULN occurred in 17 (9%) patients; 12 on concomitant valproate No patient met Hy’s law criteria. There was 1 death due to cardiopulmonary failure, deemed not treatment-related by the investigator. Median percentage reductions in TSC-associated seizures (12-week windows through 72 weeks): 53%–75%. Seizure reductions were 54%–80% for patients with a modal dose ≤25 mg/kg/day (n=145). ≥50%, ≥75%, and 100% responder rates were maintained up to 72 weeks, ranging from 52%–63%, 29%–51%, and 6%–19%, across 12-week windows. Improvement on S/CGIC was reported by 85% and 89% of subjects/caregivers at 26 and 52 weeks. Conclusions: Add-on CBD treatment was well tolerated and produced sustained reductions in TSC-associated seizures for up to 72 weeks. FUNDING: GW Research Ltd. Disclosure: 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. Dr. Bebin has received personal compensation for serving as an employee of GW Pharma. Dr. Bebin has received personal compensation for serving as an employee of Biocodex. Dr. Bebin has received personal compensation for serving as an employee of Regenxbio. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharma. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regenxbio. The institution of Dr. Bebin has received research support from GW Pharma. The institution of Dr. Bebin has received research support from NINDS. Dr. Filloux has nothing to disclose. Patrick KL Kwan, MD,PhD has nothing to disclose. Floor Jansen has nothing to disclose. Rachel Loftus has received personal compensation for serving as an employee of GW Research, Ltd. Rachel Loftus has received stock or an ownership interest from GW Research, Ltd. 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. Dr. Thiele has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GW Pharma. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for zogenix. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aquestive. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for West Therapeutics. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RegenxBio. 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 $50,000-$99,999 for serving as a Consultant for Thor labs. Dr. Thiele has received personal compensation in the range of $0-$499 for serving as a Consultant for Biocodex. The institution of Dr. Thiele has received research support from GW Pharma. The institution of Dr. Thiele has received research support from Zogenix.