CBD Without Concomitant Clobazam Reduces Seizures in Severe Epilepsy

Cannabidiol (CBD) demonstrates favorable efficacy in reducing seizures in patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), according to study findings published in the journal Seizure.

Add-on therapy of CBD to clobazam is approved in the US for treatment of LGS, DS, and tuberous sclerosis complex (TSC) in patients age 1 and older. Concomitant use of CBD with clobazam has shown significant reduction in seizures vs placebo in multiple phase 3 randomized controlled trials. As such, for the study, researchers aimed to investigate the efficacy of CBD as a standalone treatment.

The researchers conducted a retrospective phase 4 study on early access program (EAP) patients age 2 and older with LGS or DS who have been treated with CBD without clobazam between April 2021 and January 2022. The EAP provided access to CBD in those who are in urgent need for treatment, with added clobazam not being a requirement. Patients with 3 months of chart data before CBD induction without concomitant clobazam were included in the study. 

Electronic data capture was used to collect demographic and baseline information. Primary outcome was the number of seizures in the first 3 months of treatment. Follow-up was for 12 months of CBD treatment without clobazam or after discontinuation.

A total of 107 patients across 19 study sites were included in the study. Among patients with LGS and DS, the mean age was 14.5 years and 10.5 years, respectively. Concomitant use of antiseizure medications (ASMs) was recorded in 77% and 93% of patients with LGS and DS at baseline, respectively. The average daily dose of CBD without clobazam among patients with LGS and DS was 13.5 mg/kg/day and 11.6 mg/kg/day, respectively.

Patients with LGS experienced median percentage drop from baseline in seizure frequency after starting CBD treatment without concomitant clobazam of -6.2% (n=69) over 0-3 months and -16.7% (n=53) over 10-12 months. Alternatively, patients with DS did not show any median percentage change from baseline in seizure frequency over 0-3 (n=14) and 10-12 (n=8) months.

Threshold achievements of seizure reduction in patients with LGS on CBD treatment alone at 3 months were 13/69 (19%; ≥50%) and 4/69 (6%; ≥75%), and at 12 months were 16/53 (30%; ≥50%) and 9/53 (17%; ≥75%).

Patients with DS showed similar results, with threshold achievements at 3 months being 3/14 (21%; ≥50%) and 2/14 (14%; ≥75%). Achievements at 12 months were 1/8, (13%; ≥50%) and 1/8 (13%; ≥75%).

Complete seizure remission in patients with LGS was found in 1/69 (1%) of patients after 3 months and 2/53 (4%) of patients after 12 months.

Baseline seizure-free days in patients with LGS were 7.0 at baseline (n=65) and changes from baseline at 3 and 12 months were 0.8 (n=58) and 1.7 (n=44), respectively. Patients with DS had a baseline of seizure-free days of 16.9 (n=11), and baseline changes at 3 months were 1.5 (n=11) and 3.8 (n=4) at 12 months.

The incidence of adverse events (AEs) was 31%, with the most common being somnolence, seizure, diarrhea, and decreased appetite. A total of 2 patients discontinued CBD use due to AEs, and 4 patients with LGS experienced elevated liver enzymes, the researchers noted.

Limitations of the study included the lack of generalizability, as the study population of patients with LGS and DS enrolled in EAP were likely to have severe drug-resistant epilepsy.

“[O]ur findings support favorable effectiveness and retention of CBD without concomitant clobazam for up to 12 months in clinical practice,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.