Long-term Safety and Efficacy of Add-on Cannabidiol (CBD) for Seizures Associated With Tuberous Sclerosis Complex (TSC): 3-Year Results From GWPCARE6 Open-Label Extension (OLE)
Elizabeth Thiele1, E. Martina Bebin2, Francis Filloux3, Floor Jansen4, Patrick Kwan5, Rachael Loftus6, Farhad Sahebkar6, Steven Sparagana7, John lawson8, James Wheless9
1Massachusetts General Hospital, 2University of Alabama School of Medicine, 3University of Utah School of Medicine, 4Brain Center University Medical Center, 5Monash University and the University of Melbourne, 6Jazz Pharmaceuticals, Inc., 7Scottish Rite for Children and the University of Texas Southwestern Medical Center, 8Sydney Children’s Hospital, 9UTHSC-Pediatric Neurology
Objective:

To report safety for the full follow-up and efficacy through 156 weeks of CBD treatment in an OLE (NCT02544750).

Background:

Safety and efficacy of add-on CBD in TSC was demonstrated in a phase 3 randomized controlled trial (RCT; GWPCARE6 [NCT02544763]).

Design/Methods:

Patients who completed GWPCARE6 RCT were enrolled to receive CBD (Epidiolex®; 100 mg/mL oral solution), starting dose 25 mg/kg/d with titration up to maximum 50 mg/kg/d. Primary endpoint: safety. Secondary endpoints: percentage change in TSC-associated (countable focal and generalized) seizures, responder rates, and Subject/Caregiver Global Impression of Change (S/CGIC).

Results:

Of 201 RCT completers, 199 (99%) entered OLE. At baseline, median (range) age was 10.7 years (1.1–56.8) and number of ASMs was 3 (0–5). Most common concomitant ASMs were valproate (43%), vigabatrin (37%), and clobazam (35%). Baseline median (Q1, Q3) monthly TSC-associated seizure frequency: 57 (28, 109). Thirty-four patients (17%) completed treatment; most common reason for withdrawal was transition to commercial product (93 [56%]). Median (range) treatment time: 631 days (18–1462). Mean (SD) modal dose: 28 mg/kg/d (9). AEs incidence: 96% of patients, serious AEs incidence: 28%; discontinuation because of an AE: 9%. Most common AEs: diarrhea (47%), seizures (30%), pyrexia (24%), and decreased appetite (24%). Overall, 7% of patients had elevation in ALT levels and 5% in AST levels. There was 1 death due to cardiopulmonary failure, deemed not treatment related. Median percentage reduction in TSC-associated seizures (12-week windows through 156 weeks): 53%–90%. Seizure responder rates (≥50%, ≥75%, and 100%) ranged from 52%–78%, 29%–69%, and 6%–31% across 12-week windows through 156 weeks. Improvements on S/CGIC were reported by 89% and 93% of subjects/caregivers at 52 and 104 weeks.

Conclusions:

Add-on CBD treatment was well tolerated and produced sustained reductions in TSC-associated seizures for up to 156 wks in patients treated in OLE.

10.1212/WNL.0000000000202601