Long-term Efficacy and Safety of Cannabidiol (CBD) in Patients with Tuberous Sclerosis Complex (TSC): 4-year Results from the Expanded Access Program (EAP) (2405)

Objective: To evaluate the long-term efficacy (up to 192 weeks) and safety (up to 233 weeks) of add-on CBD in patients with TSC in the EAP final analysis. Background: The EAP provided open-label CBD to patients with treatment-resistant epilepsies at 35 US epilepsy centers (January 2014 through January 2019). Design/Methods: Patients received plant-derived highly purified CBD (100 mg/mL oral solution) increasing from 2–10 mg/kg/d to tolerance or maximum 25–50 mg/kg/d dose, depending on the study site. Efficacy: percentage change from baseline in convulsive, focal, and total seizure frequency and responder rates across visit windows (12-week windows through 192 weeks). Safety: adverse events (AEs). Results: Of 892 patients in the safety analysis set, 34 patients had TSC. Of those with TSC, 8 (24%) patients withdrew. Mean (range) age: 12.4 (1.8–31.2) years. Median (range) concomitant antiepileptic drugs (AEDs): 3 (1–7). Most common AEDs: clobazam (20 [59%]), lamotrigine (14 [41%]), levetiracetam (11 [32%]), and valproate (6 [18%]). Top median (Q1, Q3) CBD dose: 40 (25, 50) mg/kg/day. Baseline median (Q1, Q3) monthly seizure frequency: 46 (18, 76) for convulsive, 37 (24, 84) for focal, and 64 (31, 148) for total seizures. Median percentage reduction in seizure frequency during the first 48 weeks ranged from 48–55% for convulsive, 61–75% for focal, and 44–56% for total seizures; and the overall pattern of response was maintained through 192 weeks. Similarly, responder rates (≥50%) were maintained through 192 weeks for all seizure types. AEs were reported by 94% of patients and serious AEs by 47%; there were no deaths. Most common AEs: somnolence (32%), diarrhea (29%), convulsion (18%), and vomiting (18%). Liver-related AEs occurred in 1 patient (3%). Conclusions: Add-on CBD resulted in sustained seizure reduction in patients with TSC for up to 192 weeks with an acceptable safety profile. Funding: GW Research Ltd Disclosure: Dr. Weinstock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GW PHARMA. 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. Daniel Checketts has received personal compensation for serving as an employee of GW Research LTD. Daniel Checketts has received stock or an ownership interest from GW Research LTD. The institution of Dr. Clark has received research support from Greewich pharmaceuticals. The institution of Dr. Clark has received research support from Novartis. Dr. Szaflarski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB Pharma. Dr. Szaflarski has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for SK Life Sciences. Dr. Szaflarski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for LivaNova Inc. Dr. Szaflarski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Serina Therapeutics. Dr. Szaflarski has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Biosciences. An immediate family member of Dr. Szaflarski has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Biosciences. Dr. Szaflarski has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Seltzer has nothing to disclose. 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.