Seizure reduction was observed to be sustained for up to 192 weeks in the Expanded Access Program data.
Data from the Expanded Access Program (EAP) of cannabidiol (CBD; Epidiolex; GW Pharmaceuticals) presented at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, show that CBD provided sustained seizure reduction in patients with tuberous sclerosis complex (TSC) for up to 192 weeks with an acceptable safety profile.1
These findings were presented by Arie Weinstock, MD, director, Comprehensive Epilepsy Program, Oishei Children’s Hospital, who stated that, “in the cohort of patients with TSC in the CBD EAP, add-on CBD produced sustained reduction in convulsive, focal, and total seizure frequency through 192 weeks.”
This analysis focused on 34 patients with TSC of the 892 total patients in the safety analysis set of the GWPCARE6 EAP (NCT02544763). These 32 patients had a mean age of 12.4 years (range, 1.8–31.2) and were taking a median of 3 (range, 1–7) concomitant antiepileptic drugs (AEDS). Clobazam was the most common AED, used by 20 (59%) patients; 14 (41%) patients took lamotrigine, 11 (32%) patients took levetiracetam, and 6 (18%) took valproate.
Patients received plant-derived, highly purified CBD in doses of 2–10 mg/kg/day increasing to tolerance or a maximum of 25–50 mg/kg/day, depending on study site. The median maximum CBD dose was 40 (Q1–Q3 interquartile range [IQR], 25–50) mg/kg/day and the median duration of CBD use was 1102 (IQR, 414–1341) days. In that efficacy analysis set, the baseline median seizure frequency was 46 (IQR, 18–76) for convulsive seizures, 37 (IQR, 24–84) for focal seizures, and 64 (IQR, 31–148) for total seizures.
In the first 48 weeks, the median reduction in seizure frequency ranged from 48% to 55% for convulsive seizures, 61% to 75% for focal seizures, and 44% to 56% for total seizures. These patterns of seizure reductions were maintained through 192 weeks, with some variation due to decreasing sample size as some patients withdrew from the study. Seizure responder rates (≥50%) were also maintained through 192 weeks.
Of the 34 patients with TSC, 8 (24%) patients withdrew: 4 (12%) due to lack of efficacy, 1 (3%) due to diarrhea, and 3 (9%) due to other reasons. Adverse events (AEs) such as somnolence (32%), diarrhea (29%), convulsion (18%), and vomiting (18%) were reported by 94% of patients; 47% reported serious AEs. No deaths occurred. A liver-related AE occurred in 1 patient (3%) who had an abnormal liver function test.
“CBD was generally well tolerated with a safety profile similar to that seen in the previously reported EAP analyses and the TSC randomized controlled trial (GWPCARE6, NCT02544763). Results of this subgroup analysis from the final CBD EAP dataset support the long-term use of CBD in patients with TSC,” Weinstock and colleagues concluded.
Also presented at AES was a post-hoc analysis of GWPCARE6 that suggests that the treatment is consistent in reducing seizures in patients with TSC with and without a history of infantile spasms (IS), presented by Steven Sparagana, MD, pediatric neurologist, Texas Scottish Rite Hospital for Children, UT Southwestern Medical Center, and colleagues. In patients with a history of IS, percent reduction in seizure count from baseline was 45% for those on CBD 25 mg/kg/day (CBD25), 43% in the CBD 50 mg/kg/day (CBD50) group, and 23% for placebo compared to 54%, 55%, and 32% in the respective dose groups for those without IS history.2
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