Long-term Tolerability and Efficacy of Adjunctive Brivaracetam in Pediatric Patients with Primary Generalized Seizures: Subgroup Analysis of an Open-label, Follow-up Trial
Abstract number :
2.362
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
662
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Lieven Lagae, MD, PhD, FRCP – Member of the European Reference Network EpiCARE, University of Leuven
Christine de la Loge, MSc – UCB Pharma, Brussels, Belgium
Sami Elmoufti, MSc – UCB Pharma, Morrisville, NC, USA
Jan-Peer Elshoff, PhD – UCB Pharma, Monheim am Rhein, Germany
Brian Moseley, MD – UCB Pharma, Morrisville, NC, USA
Kristy Pucylowski, PharmD – UCB Pharma, Smyrna, GA, USA
Dimitrios Bourikas, PhD – UCB Pharma, Alimos, Greece
Rationale: A recent phase 3 trial evaluated long-term safety, tolerability, and efficacy of adjunctive brivaracetam (BRV) in pediatric patients with epilepsy for up to 9.5 years of exposure (Lagae et al. Epilepsia 2023;64:2934–46). Here we assess long-term safety, tolerability, and efficacy of adjunctive BRV in a subgroup of pediatric patients with primary generalized seizures (PGS) at baseline.
Methods: Subgroup analysis of a phase 3, open-label, long-term trial (N01266; NCT01364597) of adjunctive BRV (tablet or oral solution; max 5 mg/kg/day, not to exceed 200 mg/day) in patients with epilepsy ≥ 1 month to < 17 years of age (at core trial entry). Pre-specified seizure-related outcomes were assessed for subgroups of patients < 2 and ≥ 2 years of age (at core trial entry) using daily record card data. Kaplan-Meier-estimated retention on BRV and change in Achenbach Child Behavior Checklist (CBCL) 1.5–5/CBCL 6–18 scores were assessed post-hoc.
Results: Of the 257 patients receiving BRV in this trial (Safety Set), 68 (26.5%) patients had PGS (50.0% male; mean age: 6.7 years). 14 (20.6%) and 54 (79.4%) patients with PGS were < 2 and ≥ 2 years of age, respectively. Median modal BRV dose was 3.63 mg/kg/day. 28 (41.2%) patients with PGS completed the trial; the most common reasons for discontinuation (≥ 10% of patients) were adverse event (22.1%), lack of efficacy (17.6%), and withdrawn consent (11.8%). Kaplan-Meier-estimated retention on BRV at 12, 36, and 60 months was 61.8%, 47.7%, and 43.3%, respectively (Figure 1). Similar proportions of patients discontinued due to treatment-emergent adverse events (TEAEs) or lack of efficacy. 61 (89.7%) patients had TEAEs; 19 (27.9%) had drug-related TEAEs, 25 (36.8%) had serious TEAEs, and 15 (22.1%) discontinued due to TEAEs. In patients < 2 and ≥ 2 years of age, median percent reduction in 28-day-adjusted total seizure frequency from baseline during the evaluation period was 66.7% (n=12) and 56.9% (n=36), respectively (Full Analysis Set); 6/12 (50.0%) and 20/33 (60.6%) had a ≥ 50% response in all seizures, respectively. 2/54 (3.7%) patients ≥ 2 years of age were seizure-free during the entire evaluation period. Mean changes from baseline to last evaluation in Achenbach CBCL 1.5–5 raw syndrome scores fluctuated around 0 and were of minimal or small amplitude, suggesting stability. Mean changes from baseline to last evaluation in Achenbach CBCL 6–18 raw syndrome scores showed small improvements for most syndromes. At last evaluation, most patients remained in their baseline T-score category for each syndrome (range: 61.1%–100%; Figure 2).
Conclusions: In this subgroup analysis of a phase 3 trial, long-term adjunctive BRV was well-tolerated and efficacious in pediatric patients ≥ 1 month of age with PGS. Behavior and emotional function were generally stable (Achenbach CBCL 1.5–5) or slightly improved (Achenbach CBCL 6–18) during adjunctive BRV treatment.
Funding: UCB Pharma-sponsored
Anti-seizure Medications