Authors :
Kerstin Klotz, Dr – Freiburg Epilepsy Center, University of Freiburg; Lieven Lagae, MD, PhD – Pediatric Neurology – University Hospital KU Leuven; Andras Fogarasi, MD – Child Neurology – Bethesda Children's Hospital; Florin Floricel, MD, PhD – UCB Pharma; Christoph Reichel, PhD – UCB Pharma; Jan-Peer Elshoff, PharmD, PhD – UCB Pharma; Sofia Fleyshman, BSc, MSc – UCB Pharma; Harriet Kang, MD – Neurology – Icahn School of Medicine at Mount Sinai Hospital
Rationale: As epilepsy requires long-term treatment, it is critical to determine the long-term safety and efficacy of antiseizure medications. We evaluated the long-term safety, tolerability, and efficacy of brivaracetam (BRV) as adjunctive treatment in pediatric patients with epilepsy.
Methods: N01266 (ClinicalTrials.gov: NCT01364597) was a phase 3, open-label, multicenter, trial that enrolled patients ≥1 month to < 17 years of age with epilepsy who completed other BRV trials, and directly enrolled patients ≥4 to < 17 years of age with focal seizures. Planned trial participation was at least 3 years (until pediatric approval of BRV for the patient’s age group, establishment of a managed access program, transition to another BRV trial, or trial termination by the sponsor). Patients received adjunctive BRV as tablets/oral solution (max 5 mg/kg/day, not to exceed 200 mg/day). Primary tolerability outcomes were treatment-emergent adverse events (TEAEs) and serious TEAEs. Efficacy outcomes based on daily record card data included percent change in 28-day adjusted focal seizure frequency (patients with focal seizures only) and 50% responder rate for all seizure types, assessed from baseline to the end of the evaluation period (final evaluation/early discontinuation visit; duration of evaluation period varied between patients). Seizure assessments were performed for subgroups of patients ≥2 years of age and < 2 years of age with evaluable data. Kaplan-Meier estimated retention on BRV was also assessed.
Results: A total of 257 patients had ≥1 dose of BRV (141 [54.9%] male; mean age: 8.0 years [SD 4.5]). 36 (14.0%) patients were < 2 years of age, 15 (5.8%) were ≥2 to < 4 years of age, 141 (54.9%) were ≥4 to < 12 years of age, and 65 (25.3%) were ≥12 to 17 years of age. 185 (72.0%) patients had a history of focal seizures. Mean exposure to BRV was 3.2 patient-years; 1 patient remained in the trial for 114.3 months. 124 (48.2%) patients completed, and 133 (51.8%) patients discontinued the trial. The most common reasons for discontinuation (≥10% of patients) were lack of efficacy (39 [15.2%]), adverse event (32 [12.5%]), and withdrawn consent (29 [11.3%]). 240 (93.4%) patients had at least one TEAE and 83 (32.3%) patients had serious TEAEs (Table 1). 7 patients died during the trial; no deaths were considered treatment-related. Patients ≥2 years of age had a median decrease in 28-day adjusted focal seizure frequency of 62.9% (n=105; range −693.7, 100.0), and 81/159 (50.9%) had a 50% response in all seizures.
Patients < 2 years of age had a median decrease in 28-day adjusted focal seizure frequency of 96.9% (n=10; range 45.4, 100.0), and 15/22 (68.2%) had a 50% response in all seizures. Kaplan-Meier estimated retention on BRV at 12, 24, 36, 48, 60, and 72 months was 72.7%, 64.5%, 57.8%, 53.3%, 50.1%, and 44.8%, respectively (Table 2).
Conclusions: Long-term data demonstrated that adjunctive BRV treatment was generally well tolerated and efficacious in reducing seizure frequency in patients ≥1 month to < 17 years of age.
Funding: Sponsored by UCB Pharma