Authors :
Presenting Author: Anup D. Patel, MD – Nationwide Children’s Hospital
Jerzy P. Szaflarski, MD, PhD – University of Alabama at Birmingham; Elizabeth A. Thiele, MD, PhD – Massachusetts General Hospital; Paul Lyons, MD, PhD – Winchester Neurological Consultants; Michael Boffa, MD – Jazz Pharmaceuticals, Inc., Gentium Spa; Teresa Greco, PhD – Jazz Pharmaceuticals, Inc., Gentium Spa; Timothy Saurer, PhD – Jazz Pharmaceuticals, Inc.; Karthik Rajasekaran, PhD – Jazz Pharmaceuticals, Inc.; Kelly Simontacchi, PhD – Jazz Pharmaceuticals, Inc.
Rationale:
The CBD EAP was initiated in 2014 to provide CBD to patients with a diverse range of treatment-resistant epilepsies across 35 centers in the United States. Long-term results from the EAP showed that CBD treatment was associated with convulsive seizure reductions in the overall population, including in patients with severe genetic epilepsies. Here we specifically present the outcomes of patients diagnosed with focal epilepsy from the EAP.
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 25–50 mg/kg/d dose, depending on the site and institutional review board approval. In this analysis, patients with a diagnosis and/or etiology indicating a focal epilepsy were identified and analyzed. Efficacy data were reported as the percent change from baseline in median monthly seizure frequency for focal and total seizures through 144 weeks of treatment. Safety data were reported over the full duration of follow-up (up to 240 weeks).
Results:
From the total EAP population, 151 patients were identified as having either a confirmed focal etiology or diagnosis of focal epilepsy. At baseline, median (range) age was 16 years (1–73), and patients were taking a median (range) of 3 (0–7) antiseizure medications (ASMs); most common baseline ASMs were clobazam (36%), levetiracetam (34%), and lamotrigine (33%). Median top (Q1, Q3) CBD dose was 30 mg/kg/d (25, 41), and the median (range) exposure duration was 894 days (15–1655). For patients in the efficacy analysis set, the median (Q1, Q3) monthly seizure frequency at baseline was 27 (9, 96) for focal seizures and 56 (15, 151) for total seizures. CBD treatment was associated with a median 54%–77% reduction from baseline in focal seizures and 54%–75% reduction in total seizures during 12-week visit windows through 144 weeks of treatment (Figure). At least 50% reduction (responder rate) was reported in 51%–72% of patients for focal seizures and 50%–64% of patients for total seizures during 12-week visit windows through 144 weeks. Adverse events (AEs) were reported at any point during 240 weeks in 93% of patients and serious AEs in 38%; 8% of patients discontinued treatment due to an AE. Most common AEs (≥20% of patients) were diarrhea (47%), convulsion (25%), and somnolence (21%).
Conclusions:
In patients with focal epilepsy, adjunctive therapy with CBD was associated with a reduction in focal and total seizures through 144 weeks with an acceptable safety profile. These results provide real-world evidence of effectiveness of CBD in patients with treatment-resistant focal epilepsy.
Funding:
Jazz Pharmaceuticals, Inc.