Maintenance of Long-Term Safety and Efficacy of Cannabidiol (CBD) Treatment in Dravet Syndrome (DS): Results of the Open-Label Extension (OLE) Trial (GWPCARE5) (S19.003)

Objective: Assess long-term safety and efficacy of CBD as add-on to existing antiepileptic drug (AED) treatment in patients with treatment-resistant DS. Background: The safety and efficacy of CBD for the treatment of seizures associated with DS has been demonstrated in controlled trials. We present a prespecified interim analysis of an OLE study (GWPCARE5; NCT02224573). Design/Methods: Children and adults who participated in a 14-week, double-blind, randomized, controlled DS trial (GWPCARE1 [NCT02091375] or GWPCARE2 [NCT02224703]) could enroll to receive a pharmaceutical formulation of purified CBD (100 mg/mL) in oral solution. The primary endpoint was safety; key secondary endpoints were convulsive and total seizure frequency and the Subject/Caregiver Global Impression of Change (S/CGIC). Results: A total of 264 patients from GWCARE1 and GWPCARE2 enrolled; at time of analysis, 75 had withdrawn, 17 for adverse events (AEs). Patients were aged 3–19 years (mean, 10 years) and 50% male. Patients were taking a median of 3 concomitant AEDs. Mean modal dose for the treatment phase was 21 mg/kg/d (min=2.5, max=30; n=257). AEs occurred in 93% of patients; 64% were considered treatment-related. Of patients reporting AEs, 76% had mild/moderate AEs. Some elevations in transaminases were reported. Serious AEs were reported in 29% of patients and were considered treatment-related in 8%. There were 2 deaths; neither was deemed treatment-related. In patients with baseline data, median monthly convulsive seizures and total seizures assessed over five 12-week periods decreased by (min–max) 38%–57% (baseline=12.4) and 40%–60% (baseline=32.4), respectively. Improvements in S/CGIC scores were reported by 81% and 84% of patients/caregivers at weeks 24 and 48, respectively. Conclusions: Long-term add-on CBD treatment for DS was generally well tolerated, with an AE profile similar to that observed in controlled trials. Results showed reductions in convulsive and total seizure frequency and S/CGIC-score improvements in a high proportion of patients. Study Supported by: GW Research Ltd Disclosure: Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Insys pharmaceuticals, GWPharma, TS Alliance, DS Foundation, Visualase, Neuroblate, Zogenix, and Ultragenix. Dr. Miller has received research support from Insys pharmaceuticals, GWPharma, TS Alliance, DS Foundation, Visualase, Neuroblate, Zogenix, and Ultragenix. Dr. Devinsky has nothing to disclose. Dr. Nabbout has nothing to disclose. Dr. Laux has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GW Pharmaceuticals, Zogenix. Dr. Laux has received research support from GW Pharmaceuticals, Zogenix. Dr. Zolnowska has nothing to disclose. Dr. Wright has received compensation for serving on the Board of Directors of GW Pharmaceuticals. Dr. Roberts has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GW Research Ltd.