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)

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 \u003e3× 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. Disclosure: Dr. Thiele has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GW pharma, Zogenix, West Therapeutics, Aquestive, Biocodex. Dr. Thiele has received research support from GW Pharma and Zogenix.Dr. Bebin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences advisory board and site PI for the GW 1521 clinical trial.. Dr. Filloux has nothing to disclose. Dr. Kwan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, LivaNova, UCB Pharma. Dr. Kwan has received research support from Eisai. Dr. Loftus has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Quanticate, GW Pharmaceuticals. Dr. Sahebkar-Moghaddam has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences, Inc..Dr. Sparagana has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences--ad. board consulting (honorarium). Dr. Sparagana has received research support from All funds to my institution: Greenwich Biosciences, Novartis, Tuberous Sclerosis Alliance. Dr. Wheless has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CombiMatrix; Eisai Inc.; GW Pharmaceuticals; Lundbeck, Inc.; Neurelis, Inc.; NeuroPace, Inc.; Supernus Pharmaceuticals, Inc.; and Upsher-Smith Laboratories, Inc. Dr. Wheless has served as a speaker or a member of a speakers bureau for: Cyberonics, Inc.; E. Dr. Wheless has received research support from Acorda Therapeutics; GW Pharmaceuticals; INSYS Therapeutics, Inc.; Lundbeck, Inc.; Mallinckrodt; Neurelis, Inc.; NeuroPace, Inc.; Upsher-Smith Laboratories, Inc.; and Zogenix, Inc.