Authors :
Presenting Author: Jerzy Szaflarski, MD, PhD – University of Alabama Birmingham, Birmingham, AL, USA
Timothy B. Saurer, 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; Sheryl R. Haut, MD – Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA
Rationale:
The CBD EAP was initiated in 2014 to provide compassionate access to CBD for patients with diverse treatment-resistant epilepsies (TREs). Four-year results from the overall EAP population (mean age, 13.5 y) have been previously published and reported sustained seizure reduction associated with long-term CBD use. Here, we present the effectiveness and safety results in adult patients (aged ≥ 18 y) from the EAP.
Methods:
Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/mL oral solution) starting at 2–10 mg/kg/d and titrated up to tolerance or maximum of 25–50 mg/kg/d, at the discretion of the study site. Effectiveness of CBD was evaluated as the percentage change from baseline in median monthly frequency of convulsive and total seizures (convulsive plus nonconvulsive seizures, including focal seizures with or without impaired awareness), and the ≥ 50%, ≥ 75%, and 100% responder rates through 144 weeks of treatment. Safety results are reported for the full follow-up.
Results:
Of 892 patients in the overall safety analysis set, 193 (22%) were adults, with mean age (range) of 27.3 (18.0–74.5) y. Patients were taking a median (range) of three (1–7) antiseizure medications (ASMs) at baseline. The most common ASMs were clobazam (37%), levetiracetam (34%), and lamotrigine (33%). Among adults, 64 (33%) withdrew; most commonly due to lack of efficacy (20%) or adverse events (AE; 5%). Median (range) CBD exposure was 733 (15–1742) days, and the median (IQR) top CBD dose was 25 (21–35) mg/kg/d. In the efficacy analysis set (n=182), baseline median (IQR) monthly frequency of convulsive and total seizures was 22 (6–60) and 40 (15–100), respectively. CBD treatment was associated with a median percent reduction from baseline of 45%–64% in convulsive seizures and 41%–63% in total seizures across 12-week visit intervals through 144 weeks of treatment (Figure 1). Convulsive seizure responder rates (≥ 50%, ≥ 75%, and 100% reduction) were maintained through 144 weeks and ranged from 49%–64%, 27%–39%, and 7%–16% of patients across visit intervals, respectively (Figure 2A). Total seizure responder rates showed sustained and profound reductions of ≥ 75% among 25%–38% of patients across visit intervals (Figure 2B). AEs were reported in 92% of patients and serious AEs in 39%; 8% of patients withdrew because of an AE. There were two deaths during the study, both deemed unrelated to treatment. Most common treatment-related AEs (≥ 20% of patients) were diarrhea (49%) and somnolence (24%). Liver-related AEs in > 1% of patients were increased ALT, increased AST, and abnormal liver function test (5% each).
Conclusions:
Among adults with TREs, add-on CBD was associated with sustained seizure reduction through 144 weeks with an acceptable safety profile. These results support the long-term use of CBD for adults with TRE in a real-world setting and provide insight into the safety and effectiveness of CBD when used in clinical practice.
Funding:
Jazz Pharmaceuticals, Inc.