Tolerability and Efficacy of Adjunctive Brivaracetam in Japanese and Chinese Patients with Focal-onset Seizures: Interim and Post Hoc Analysis of a Phase 3, Open-label Extension Trial
Abstract number :
3.409
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
84
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Ayataka Fujimoto, MD.PhD. – Seirei Hamamatsu General Hospital
Bing Qin, MD – The First Affiliated Hospital of Jinan University, Guangdong, China
Dong Zhou, MD – West China Hospital, Sichuan University
Dimitrios Bourikas, PhD – UCB Pharma, Alimos, Greece
Najla Dickson, MD – UCB Pharma, Morrisville, NC, USA
Brian Moseley, MD – UCB Pharma, Morrisville, NC, USA
Tomonobu Sano, MS – UCB Pharma, Tokyo, Japan
Tadaharu Soma, - – UCB Pharma, Tokyo, Japan
Weiwei Sun, M.Med – UCB Pharma, Shanghai, China
Jun Watanabe, PhD – UCB Pharma, Tokyo, Japan
Yushi Inoue, MD, PhD – NHO Shizuoka institute of epilepsy and neurological disorders
Rationale: This trial evaluated the long-term safety, tolerability, and maintenance of efficacy of adjunctive brivaracetam (BRV) in Japanese and Chinese patients aged ≥ 16 years with focal-onset seizures (FOS).
Methods: Interim analysis of data from EP0085 (NCT03250377), an ongoing, open-label, long-term follow-up trial of adjunctive BRV 50–200 mg/day in Japanese and Chinese patients after all ongoing patients had been exposed to BRV for ≥ 48 weeks. The primary safety outcome is the incidence of treatment-emergent adverse events (TEAEs). Post hoc analyses included the change in number of concomitant antiseizure medications (ASMs) and BRV daily dose during the initial 12 months in the trial, and the Kaplan-Meier (KM) estimated proportion of patients not discontinuing BRV due to any reason, lack of efficacy, TEAEs, or lack of efficacy or TEAEs over time. For patients who rolled over into EP0085, baseline was the baseline period of the core trial (EP0083/NCT03083665 or N01358/NCT01261325). For direct enrollers, the baseline period was the 8 weeks before BRV initiation.
Results: At data cutoff (June 1, 2023), 207 patients had enrolled (Japan: 132 [63.8%]; China: 75 [36.2%]); of these, 157 (75.8%) were ongoing, and 50 (24.2%) had discontinued. Mean age was 36.7 (SD 14.1) years, and 107 (51.7%) patients were female. Median duration of epilepsy was 14.73 (IQR 7.22, 24.93) years. Overall, the median number of concomitant ASMs was 2 (range 1–7) from trial entry through 12 months of treatment. At data cutoff, the total duration of BRV exposure was 378.5 patient-years. The mean duration of BRV exposure was 667.8 days (SD 492.1 days; median 427.0 days), with a median modal dose of 200 mg/day (range 25–200 mg/day). The median daily dose of BRV was 100 mg/day at trial entry, then increased gradually and reached a median of 200 mg/day after 9 months of treatment. TEAEs were reported by 184 (88.9%) patients; drug-related TEAEs: 60 (29.0%); serious TEAEs: 29 (14.0%); and discontinuations due to TEAEs: 8 (3.9%). Median FOS frequency per 28 days decreased from 7.59 (IQR 4.39, 20.00) during baseline to 4.11 (IQR 1.56, 11.79) during the evaluation period. BRV retention rates at 1, 2, and 3 years were 85%, 76%, and 68%, respectively (Figure). The KM estimated proportion of patients discontinuing due to TEAEs was low over 5 years of treatment (≤ 5%). Most of the discontinuations due to TEAEs were during the first 12 months of treatment.
Conclusions: Based on this interim and post hoc analysis, long-term adjunctive BRV was well-tolerated and efficacious in Japanese and Chinese patients with FOS. Overall, 68% of patients remained on BRV treatment for 3 years. Over 5 years of treatment, the estimated proportion of patients discontinuing due to TEAEs was low (≤ 5%).
Funding: UCB Pharma-sponsored
Anti-seizure Medications