Long-term Tolerability and Retention of Adjunctive Brivaracetam in Children With Primary Generalized or Mixed Seizure Types: Interim Subgroup Analysis of Pooled Data From two Open-label Trials

Objective: Assess tolerability and retention rate (effectiveness) of adjunctive brivaracetam in children with primary generalized seizures (PGS) or mixed seizure types. Background: In US, brivaracetam is indicated for treatment of focal seizures in patients aged ≥4years. Design/Methods: Pooled interim analysis (cut-off March 15, 2017) of children with PGS or mixed seizure types enrolled in N01263 (NCT00422422), an open-label trial of adjunctive brivaracetam in children aged ≥1month to Results: Fifty-one children with PGS or mixed seizure types were enrolled (mean age 5.6years; 54.9% female; mean epilepsy duration 3.4years). Median numbers of prior and concomitant AEDs were 3.0 and 2.0. Median brivaracetam exposure duration was 541days; median modal dose was 4.0mg/kg/day (equivalent to 200mg/day for patients ≥50kg). At cut-off, 20 (39.2%) were ongoing, 29 (56.9%) had discontinued (main reasons: adverse event [21.6%], lack of efficacy [17.6%], caregiver choice [11.8%]). Forty-eight (94.1%) patients experienced ≥1 treatment-emergent adverse event (TEAE), most commonly (≥20%) nasopharyngitis (31.4%), pyrexia (29.4%), and upper respiratory tract infection, diarrhea, convulsion, vomiting (23.5% each). Nineteen (37.3%) experienced drug-related TEAEs, mostly (≥5%) somnolence (9.8%), decreased appetite (7.8%), fatigue (5.9%). Eleven (21.6%) discontinued due to TEAEs. Two (3.9%) died (acute respiratory failure/aspiration/circulatory collapse and pneumonia); neither death was considered brivaracetam-related. Kaplan-Meier estimated 12- and 24-month retention rates were 56.9% (95% CI 42.2–69.1) and 47.1% (33.0–59.9). Conclusions: Long-term adjunctive brivaracetam was generally well tolerated in children with PGS or mixed seizure types with a safety profile consistent with that reported in children with focal seizures only. Two-year retention rate (approximately 50%) suggests potential treatment benefit in this pediatric population. Additional studies are needed. Disclosure: Dr. Patel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences and Medscape. Dr. Patel has received research support from Investigator on GW Research Ltd.Dr. Gasalla has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma. Dr. Gasalla holds stock and/or stock options in UCB. Dr. Nondonfaz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Yes. UCB Pharma employee.. Dr. Nondonfaz holds stock and/or stock options in UCB Pharma stocks. Dr. Elmoufti has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma. Dr. Elshoff has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma. Dr. Elshoff holds stock and/or stock options in UCB Pharma.