Cannabidiol Effective in TSC Regardless of Infantile Spasm History

Steven Sparagana, MD

Post-hoc analysis from the phase 3 GWPCARE6 trial (NCT02544763) of cannabidiol (CBD; Epidiolex; GW Pharmaceuticals) suggest that the treatment is consistent in reducing seizures in patients with tuberous sclerosis complex (TSC) with and without a history of infantile spasms (IS).¹

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.

The data were presented at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, by Steven Sparagana, MD, pediatric neurologist, Texas Scottish Rite Hospital for Children, UT Southwestern Medical Center.

The placebo-adjusted reduction was 29% (95% CI, 6–45) for CBD25 and 25% (95% CI, 3–43) for CBD50 in those with IS history, whereas, for patients without IS history, the placebo-adjusted reduction was 32% (95% CI, 5–52) for CBD25 and 34% (95% CI, 7–54) for CBD50, respectively. The treatment effect was comparable on effect modification analysis between patients with and without IS history (CBD25 interaction P = .803; CBD50 interaction P = .561).

READ MORE: Cannabidiol Efficacy Confirmed in Lennox-Gastaut Syndrome

Patients included in the study were between 1 and 65 years of age, had treatment-resistant epilepsy, ≥8 TSC-associated seizures during the 4-week baseline, and were taking ≥1 antiseizure medications (ASMs). Of the 224 patients enrolled, 138 (62%) had IS history. The median age for patients with IS history was 12.2 years (range, 1.1–56.8) compared to 10.5 years (range, 1.6–55.8) for those without.

Researchers randomized patients to either CBD25, CBD50, or placebo, and evaluated percent reduction from baseline in TSC-associated seizure count in both patients with and without IS history. IS history was defined as having documentation of current or prior infantile/epileptic spasms with onset age ≤2 years.

In total, 93%, 100%, and 95% of patients in the CBD25, CBD50, and placebo groups, respectively, reported adverse events (AEs). Among them, diarrhea (CBD25, 31% [n = 23]; CBD50, 56% [n = 41]) and somnolence (CBD25, 13% [n = 10]; CBD50, 19% [n = 26]) were the most common, occurring more frequently with CBD than placebo (diarrhea: 19% [n = 25]; somnolence: 9% [n = 7]).

Alanine transaminase (ALT) and aspartate aminotransferase (AST) elevations occurred in 9 (12%) patients on CBD25, 19 (26%) on CBD50, and none on placebo. Notably, the use of concomitant valproate was in 79% of these patients.

CBD was first approved by the FDA in June 2018 for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) and was later expanded to include an indication for patients with TSC.^2,3

The basis of the new indication was from the original GWPCARE6 trial, which met its primary end point, with patients treated with either dose of CBD experiencing a 48% reduction in seizure frequency compared with 24% in the placebo group (P <.01).⁴

Those who took CBD were more likely to experience at least a 50% reduction in seizures, observed in 36% of the 25 mg group (P = .0692) and 40% of the 50 mg group (P = .0245) compared with 22% for placebo. Caregivers reported an overall improvement in 69% of those taking CBD25, 62% of those taking CBD50, and 40% of those who received placebo.

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REFERENCES
1. Sparagana S, Kwan P, O’Callaghan FJ, et al. Efficacy of add-on cannabidiol (CBD) treatment in patients with tuberous sclerosis complex (TSC) and a history of infantile spasms (IS): post hoc analysis of phase 3 trial GWPCARE6. Presented at AES 2020 Virtual Meeting: December 4–8, 2020. Abstract 125.
2. Devinsky O, Patel AD, Cross JH, et al. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018; 378:1888-1897
3. FDA approves Epidiolex (cannabidiol) oral solution to treat seizures associated with tuberous sclerosis complex. News release. GW Pharmaceuticals. August 3, 2020. Accessed August 3, 2020. https://www.globenewswire.com/news-release/2020/08/03/2071601/0/en/FDA-Approves-EPIDIOLEX-cannabidiol-Oral-Solution-to-Treat-Seizures-Associated-with-Tuberous-Sclerosis-Complex.html
4. Thiele E, Wong M. Cannabidiol (CBD) treatment in patients with seizures associated with tuberous sclerosis complex: a randomized, double-blind, placebo-controlled phase 3 trial (GWPCARE6). Presented at: AES 2019, December 7–10, 2020; Baltimore, Maryland. Abstract 1.293.