Real-world Outcomes of Cannabidiol (CBD) in Tuberous Sclerosis Complex (TSC) and Other Focal Epilepsies: Experience from the Expanded Access Program (EAP)
Abstract number :
2.369
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
1004
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Anup Patel, MD, FAAN, FAES – Nationwide Children's Hospital, The Ohio State University
Jerzy Szaflarski, MD, PhD – University of Alabama
Presenting Author: Elizabeth Thiele, MD, PhD – Massachusetts General Hospital
Paul D. Lyons, MD, PhD – Winchester Neurological Consultants
Michael Boffa, MD, FAES – Jazz Pharmaceuticals, Inc
Teresa Greco, PhD – Jazz Pharmaceuticals, Inc
Timothy Saurer, PhD – Jazz Pharmaceuticals, Inc.
Karthik Rajasekaran, PhD – Jazz Pharmaceuticals, Inc.
Kelly Simontacchi, PhD – Jazz Pharmaceuticals, Inc.
Rationale: Efficacy of CBD in seizures associated with TSC, a condition with mainly focal seizures, was demonstrated in a phase 3 trial. Long-term CBD treatment in the EAP was also associated with seizure reduction in various treatment-resistant focal epilepsies. Here we present CBD treatment outcomes in patients with TSC (TSC group) vs those with other types of focal epilepsy (non-TSC group).
Methods: Patients received plant-derived, highly purified CBD (Epidiolex®; 100 mg/mL oral solution), increasing from 2–10 mg/kg/d to tolerance or maximum of 25–50 mg/kg/d, depending on the study site. Effectiveness was evaluated as percent change from baseline in median monthly focal and total seizure frequencies and responder rates (RR) across 12-week windows through 144 weeks of treatment. Safety data are reported for the complete follow-up (up to 240 weeks).
Results: Of 146 patients with focal epilepsy, 34 (23%) had TSC and 112 (77%) had other focal epilepsies, with cortical dysplasia (14%), frontal lobe epilepsy (10%), and malformation of cortical development (9%) as the most common causes. At baseline, the median (range) patient age was 12 years (2–31) in the TSC group and 17 years (2–73) in the non-TSC group; the median (range) numbers of antiseizure medications (ASMs) were 3 (1–7) and 3 (0–5), respectively. Most common baseline ASMs were clobazam (53%), lacosamide (50%), and lamotrigine (44%) in the TSC group and levetiracetam (34%), clobazam (33%), and lamotrigine (29%) in the non-TSC group. Median (Q1, Q3) total daily CBD dose was 25 mg/kg/d (17, 35) for the TSC group and 24 mg/kg/d (15, 27) for the non-TSC group; median (range) exposure was 1102 days (85–1631) and 880 days (15–1655), respectively. At baseline, the median (Q1, Q3) monthly focal and total seizure frequencies were 41 (25, 86) and 66 (36, 164), respectively, for the TSC group, and 20 (8, 104) and 51 (10, 151) for the non-TSC group. CBD was associated with a median reduction from baseline of 51%–87% in focal seizures and 44%–87% in total seizures in the TSC group and with 46%–75% and 46%–74% median reductions from baseline in the non-TSC group (Fig 1). The ≥ 50% RRs were similar between the groups for both focal and total seizures (Fig 2). Adverse events (AEs) occurred in 88% of patients in the TSC group and 94% in the non-TSC group; serious AEs occurred in 41% and 38% of patients, respectively. AEs leading to CBD discontinuation occurred in 6% and 9% of patients in the TSC and non-TSC groups, respectively. The most common AEs were somnolence (32%) in the TSC group and diarrhea (52%) in the non-TSC group.
Conclusions: CBD treatment was associated with similar reductions in focal and total seizure frequencies in both the TSC and non-TSC groups. The safety profile in both groups was consistent with that observed in other studies of CBD. These results demonstrate the real-world outcomes of CBD in patients with various treatment-resistant focal epilepsies and suggest that CBD has similar effectiveness in focal epilepsy regardless of focal epilepsy type.
Funding: Jazz Pharmaceuticals, Inc.
Anti-seizure Medications