Long-term Effectiveness of Cannabidiol (CBD) Against Focal-Onset Seizures in Treatment-Resistant Epilepsies (TRE)

Abstract number : 3.291
Submission category : 7. Anti-seizure Medications / 7E. Other
Year : 2023
Submission ID : 1029
Source : www.aesnet.org
Presentation date : 12/4/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Yong D. Park, MD – Medical College of Georgia at Augusta University, Department of Neurology, AU Health System, Augusta, GA, USA

Karthik Rajasekaran, PhD – Jazz Pharmaceuticals, Inc, Carlsbad, CA, USA; Teresa Greco, MD, PhD – Jazz Pharmaceuticals, Inc, Gentium Srl, Villa Guardia, Italy; Farhad Sahebkar, MD – Jazz Pharmaceuticals, Inc, Carlsbad, CA, USA; Robert J. Flamini, MD – PANDA Neurology, Atlanta, GA, USA

Patients with TRE received compassionate access to CBD through the Expanded Access Program (EAP). Four-year results from the EAP demonstrated that CBD was associated with sustained seizure improvement. We report the effect of CBD in EAP patients with focal-onset seizures, including focal aware seizures (FAS), focal impaired awareness seizures (FIAS), and focal to bilateral tonic-clonic seizures (FBTCS).

Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) starting at 2–10 mg/kg/d and further titrated based on clinical response and tolerance to a maximum of 25–50 mg/kg/d, depending on the study site. Effectiveness of CBD was evaluated as the percentage change from baseline in the median monthly frequency of focal seizures, and responder rates (≥ 50%, ≥ 75%, and 100% reduction) across 12-wk intervals through 144 wks of treatment. Safety results are reported for the full follow-up.

Out of 892 patients in the overall EAP, 351 (39%) experienced focal seizures. The mean age was 15.8 years (range, < 1–73.2), and patients were taking a median of three antiseizure medications (ASMs) at baseline (range, 0–10). The most common ASMs were clobazam (43%), levetiracetam (35%), lacosamide (27%), and lamotrigine (26%). Among patients with focal seizures, 113 (32%) withdrew, primarily due to lack of efficacy (18%) or adverse events (AE; 5%). The median CBD exposure was 684 days (range, 10–1793), and the median top CBD dose was 25 mg/kg/d (IQR, 24–31). Baseline median monthly seizure frequency was 28 (IQR, 4–87) for FAS, 22 (IQR, 7–76) for FIAS, and 12 (IQR, 4–41) for FBTCS. CBD treatment was associated with median reduction of 67%–99% in FAS, 61%–78% in FIAS, and 50%–81% in FBTCS across 12-wk intervals through 144 wks (Fig. 1). The responder rates (RR) for FAS through 144 wks were 61%–88% for ≥ 50% reduction, 45%–72% for ≥ 75% reduction, and 20%–46% for 100% reduction (Fig. 2A). For FIAS, the RR ranged from 55%–69%, 41%–56%, and 18%–29% in the respective categories (Fig. 2B). For FBTCS, the RR in the respective categories ranged from 52%–69%, 41%–54%, and 23%–36% (Fig. 2C). Among patients with any focal seizure, 90% reported AEs, with 38% experiencing serious AEs. Seven percent of patients withdrew due to AEs. Five deaths occurred in the cohort, unrelated to treatment according to the investigator. The most common AEs (≥ 20% of patients) were diarrhea (40%), convulsion (24%), and somnolence (21%). Liver-related AEs in more than 1% of patients included increased ALT and AST (4% each) and abnormal liver function test (3%).
Anti-seizure Medications