Long-Term CBD Treatment in Tuberous Sclerosis Complex Effective Regardless of Age

John A. Lawson, PhD

New data from the open-label extension (OLE) of the phase 3 GWPCARE6 trial (NCT02544763) showed that treatment with cannabidiol, or CBD (Epidiolex; Jazz Pharmaceuticals), was effective in patients with tuberous sclerosis complex (TSC) regardless of age. Overall, the efficacy was maintained over the long-term period, with subgroup safety findings that were consistent with the overall population.¹

These data were presented at the 2023 American Epilepsy Society (AES) annual meeting, held December 1-5, in Orlando, Florida, by lead investigator John A. Lawson, PhD, a conjunct senior lecturer at the University of New South Wales. In the double-blind portion of the study, patients received CBD oral solution at 25 mg/kg/d (CBD25) or 50 mg/kg/d (CBD50) or placebo for a 4-week titration period followed by a 12-week maintenance period. Of the 224 patients included in this part of the trial, 166 (74%)(CBD25: n = 55; CBD50: n = 55; placebo: n = 56) were pediatric and 58 (26%)(CBD25: n = 20; CBD50: n = 18; placebo: n = 20) were adult.

In total, 153 (92%) pediatric and 46 (79%) adult patients continued to the OLE where they all received CBD for the maximum dose up to 50 mg/kg/d. Between pediatric and adult patients, median treatment duration was 680 and 383 days, respectively. The post-hoc analysis used TSC-associated seizure responder rates of at least 50% and 75% reduction for the efficacy analysis.

During the randomized portion of the study, 47% of pediatric patients taking CBD25, 52% taking CBD50, and 21% taking placebo had at least a 50% reduction in seizure frequency. Rates for adults were similar, with 50% of patients in both the CBD25 and CBD50 groups, respectively, as responders to treatment vs 25% of those on placebo. TSC-associated seizure reductions of at least 75% were reported in 24% of pediatric patients on CBD25, 28% taking CBD50, and 5% on placebo. For adults, 20% of those on CBD25, 31% on CBD50, and 5% taking placebo demonstrated such significant reductions as well.

Throughout the OLE, a response of at least 50% was observed in 53% of pediatric patients and 54% of adult patients. Similarly, 33% of patients in both groups reported at least a 75% reduction in TSC-associated seizures. In terms of safety, adverse events (AEs) were reported in 96%, 100%, and 95% of pediatric patients and 85%, 100%, and 95% of adult patients taking CBD25, CBD50, and placebo, respectively, during the randomized portion of the study. Throughout the OLE, AEs were recorded in 97% of pediatric patients and 91% of adult patients.

CBD was originally approved to treat patients with Lennox-Gastaut syndrome and Dravet syndrome, 2 rare epileptic disorders in 2019, and later for TSC in 2020.² Data from the double-blind portion of GWPCARE6, published in JAMA Neurology, served as the basis for the approval. In the study, the percentage reduction from baseline in the types of seizures considered the primary end point was 48.6% (95% CI, 40.4-55.8%) for the CBD25 group, 47.5% (95% CI, 39.0-54.8%) for the CBD50 group, and 26.5% (95% CI, 14.9-36.5%) for the placebo group. Overall, the 25-mg/kg/d dosage had a better safety profile than the 50 mg/kg/d dosage.³

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REFERENCES
1. Lawson JA, Kotulska K, Sahebkar F, Saurer TB. Efficacy and safety of cannabidiol (CBD) for seizures associated with tuberous sclerosis complex (TSC) in pediatric and adult patients from GWPCARE6: a phase 3 trial with open-label extension (OLE). Presented at: AES 2023; December 1-5; Orlando, FL. POSTER 3.266
2. FDA approves new indication for drug containing an active ingredient derived from cannabis to treat seizures in rare genetic disease. News release. FDA. July 31, 2020. Accessed November 30, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-indication-drug-containing-active-ingredient-derived-cannabis-treat-seizures-rare
3. Thiele EA, Bebin ME, Bhathal H, et al. Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex: a placebo-controlled randomized clinical trial. JAMA Neurol. 2021;78(3):285-292. doi:10.1001/jamaneurol.2020.4607