The GW Pharmaceuticals product resulted in nearly 50% reductions in seizures at both 25 mg/kg and 50 mg/kg dose groups.
Elizabeth Thiele, MD, PhD
GW Pharmaceuticals has announced the publication of the phase 3 clinical trial data from its assessment of cannabidiol, or CBD (Epidiolex), in the treatment of patients with tuberous sclerosis complex (TSC).1 The data, published in JAMA Neurology, suggest that the first approved plant-derived cannabis-based medicine can significantly reduce seizures.
Those treated with 25 mg/kg/day or 50 mg/kg/day reported significantly greater reductions in TSC-associated seizures (25 mg/kg: 48.6%; 50 mg/kg: 47.5%) compared to placebo (26.5%; P <.001 and P = .002, respectively).2
“People living with TSC may experience focal seizures and spasms as infants and continue to suffer from seizures throughout their lifetime,” lead investigator Elizabeth Thiele, MD, PhD, director of pediatric epilepsy and director, The Carol and James Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital; and professor of neurology at Harvard Medical School, said in a statement. “This study demonstrated that for patients with TSC and a high baseline burden of treatment-resistant, primarily focal, seizures, Epidiolex significantly reduced the frequency of seizures compared with placebo.”
The secondary end point data additional showed that larger percentages of patients on CBD experienced ≥50% reduction in seizures (25 mg/kg: 36%; 50 mg/kg: 40%) compared to placebo (22%; P = .07 and P = .02, respectively). As well, both dose groups reported greater reductions in total seizure frequency (48%) compared to placebo (27%; P <.001 and P = .002, respectively).
Caregivers and patients also reported overall improvement, as measured by subject/caregiver global impression of change (S/CGIC), more often with the treatment (35 mg/kg: 69%; 50 mg/kg: 62%) than with placebo (39%; P = .007 and P = .06, respectively).
The observed safety profile was deemed consistent with prior studies, with both groups reporting an acceptable safety profile (25 mg/kg: 93%; 50 mg/kg: 100%; placebo: 95%). There were fewer adverse events (AEs) reported with 25 mg/kg/day than 50 mg/kg/day, and the most common AEs were diarrhea, decreased appetite, and somnolence. Elevated liver enzymes were reported in 12% of 25 mg/kg/day patients and 26% of 50 mg/kg/day patients. Of those, 79% were also taking valproate. All elevations resolved.
CBD was approved for the treatment of patients with TSC in July 2020—the basis for which was provided by these data—indicated for use in patients age 1 and older with TSC. Notably, at that time, the FDA also expanded the approved age range to patients age 1 and older for the treatment’s other indications, including treatment of Dravet syndrome and Lennox-Gastaut syndrome (LGS).
“The publication of these results in JAMA Neurology reinforces the importance of Epidiolex as a new treatment option for people experiencing treatment-resistant seizures associated with TSC,” said Justin Gover, chief executive officer, GW Pharmaceuticals, in a statement. “We hope that the data will help clinicians to better understand the potential of Epidiolex to reduce focal and generalized seizure frequency in their patients with this condition.”
Previously, some of the results were presented at the 2019 meeting of the American Epilepsy Society (AES). Additionally, at the 2020 AES meeting, trial data from the Expanded Access Program (EAP) were presented suggesting that CBD provided sustained seizure reduction in patients with TSC for up to 192 weeks with an acceptable safety profile.3
Those 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.” The 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.
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.4
1. JAMA Neurology Publishes Phase 3 Study of EPIDIOLEX® (cannabidiol) Oral Solution in Patients with Seizures Associated with Tuberous Sclerosis Complex. News release. GW Pharmaceuticals. Published December 21, 2020. Accessed January 7, 2021. https://www.globenewswire.com/news-release/2020/12/21/2148882/0/en/JAMA-Neurology-Publishes-Phase-3-Study-of-EPIDIOLEX-cannabidiol-Oral-Solution-in-Patients-with-Seizures-Associated-with-Tuberous-Sclerosis-Complex.html
2. Thiele EA, Bebin M, Bhathal H, et al. Add-On Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurol. Published online December 21, 2020. doi:10.1001/jamaneurol.2020.4607
3. Weinstock A, Bebin EM, Checketts D, et al. Long-term efficacy and safety of cannabidiol (CBD) in patients with tuberous sclerosis complex (TSC): 4-year results from the expanded access program (EAP). Presented at AES 2020 Virtual Meeting: December 4–8, 2020. Abstract 137.
4. 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.