PDF(Pubmed)
Abstract：
One third of patients with epilepsy will continue to have uncontrolled seizures despite treatment with antiseizure medications (ASMs). There is therefore a need to develop novel ASMs. Brivaracetam (BRV) is an ASM that was developed in a major drug discovery program aimed at identifying selective, high-affinity synaptic vesicle protein 2A (SV2A) ligands, the target molecule of levetiracetam. BRV binds to SV2A with 15- to 30-fold higher affinity and greater selectivity than levetiracetam. BRV has broad-spectrum antiseizure activity in animal models of epilepsy, a favorable pharmacokinetic profile, few clinically relevant drug-drug interactions, and rapid brain penetration. BRV is available in oral and intravenous formulations and can be initiated at target dose without titration. Efficacy and safety of adjunctive BRV (50-200 mg/day) treatment of focal-onset seizures was demonstrated in three pivotal phase III trials (NCT00490035/NCT00464269/NCT01261325), including in patients who had previously failed levetiracetam. Efficacy and safety of adjunctive BRV were also demonstrated in adult Asian patients with focal-onset seizures (NCT03083665). In several open-label trials (NCT00150800/NCT00175916/NCT01339559), long-term safety and tolerability of adjunctive BRV was established, with efficacy maintained for up to 14 years, with high retention rates. Evidence from daily clinical practice highlights BRV effectiveness and tolerability in specific epilepsy patient populations with high unmet needs: the elderly (≥ 65 years of age), children (< 16 years of age), patients with cognitive impairment, patients with psychiatric comorbid conditions, and patients with acquired epilepsy of specific etiologies (post-stroke epilepsy/brain tumor related epilepsy/traumatic brain injury-related epilepsy). Here, we review the preclinical profile and clinical benefits of BRV from pivotal trials and recently published evidence from daily clinical practice.
One in three people with epilepsy continue to have seizures despite treatment. Brivaracetam is a medicine used to treat seizures in people with epilepsy. It binds to a protein in the brain (synaptic vesicle protein 2A) and is effective in many different animal models of epilepsy. Brivaracetam enters the brain quickly. It has few interactions with other medicines, which is important because people with epilepsy may be taking additional medicines for epilepsy or other conditions. Brivaracetam is available as tablets, oral solution, and solution for intravenous injection, can be started at the recommended target dose, and is easy to use. In three phase III trials, people with uncontrolled focal-onset seizures taking brivaracetam 50–200 mg each day had fewer seizures than people taking a placebo. Brivaracetam was tolerated well. It also worked well in many people who had previously not responded to antiseizure medications. The efficacy of brivaracetam treatment is maintained for up to 14 years. Brivaracetam treatment reduces seizures in the elderly (≥ 65 years old), in children (< 16 years old), in people with cognitive or learning disabilities, in people with additional psychiatric conditions, and in people with different causes of epilepsy (post-stroke epilepsy, brain-tumor related epilepsy, and traumatic brain injury-related epilepsy). Here, we review brivaracetam characteristics and the results when people with epilepsy received brivaracetam in key clinical trials and real-world studies in daily clinical practice.
One in three people with epilepsy continue to have seizures despite treatment. Brivaracetam is a medicine used to treat seizures in people with epilepsy. It binds to a protein in the brain (synaptic vesicle protein 2A) and is effective in many different animal models of epilepsy. Brivaracetam enters the brain quickly. It has few interactions with other medicines, which is important because people with epilepsy may be taking additional medicines for epilepsy or other conditions. Brivaracetam is available as tablets, oral solution, and solution for intravenous injection, can be started at the recommended target dose, and is easy to use. In three phase III trials, people with uncontrolled focal-onset seizures taking brivaracetam 50–200 mg each day had fewer seizures than people taking a placebo. Brivaracetam was tolerated well. It also worked well in many people who had previously not responded to antiseizure medications. The efficacy of brivaracetam treatment is maintained for up to 14 years. Brivaracetam treatment reduces seizures in the elderly (≥ 65 years old), in children (< 16 years old), in people with cognitive or learning disabilities, in people with additional psychiatric conditions, and in people with different causes of epilepsy (post-stroke epilepsy, brain-tumor related epilepsy, and traumatic brain injury-related epilepsy). Here, we review brivaracetam characteristics and the results when people with epilepsy received brivaracetam in key clinical trials and real-world studies in daily clinical practice.
摘要：
尽管使用抗癫痫药物（ASM）进行治疗，但仍有三分之一的癫痫患者将继续出现不受控制的癫痫发作。因此，需要开发新的ASM。Brivaracetam（BRV）是一种ASM，它是在一个主要的药物发现计划中开发的，旨在鉴定选择性，高亲和力突触囊泡蛋白2A（SV2A）配体，左乙拉西坦的靶分子。BRV与SV2A结合的亲和力比左乙拉西坦高15至30倍，选择性更高。BRV在癫痫动物模型中具有广谱抗癫痫活性，良好的药代动力学特征，很少有临床相关的药物-药物相互作用，和快速的大脑渗透。BRV可用于口服和静脉内制剂，并且可以在目标剂量下开始，无需滴定。三项关键III期试验（NCT00490035/NCT00464269/NCT01261325）证明了辅助BRV（50-200mg/天）治疗局灶性发作性癫痫的有效性和安全性，包括以前左乙拉西坦失败的患者。辅助BRV的有效性和安全性也在局灶性发作的成年亚洲患者中得到证实(NCT03083665)。在几个开放标签试验（NCT00150800/NCT00175916/NCT01339559）中，建立了辅助BRV的长期安全性和耐受性，疗效维持长达14年，保留率高。来自日常临床实践的证据强调了特定癫痫患者人群的BRV有效性和耐受性，这些患者具有高度未满足的需求：老年人（≥65岁），儿童（<16岁），认知障碍患者，患有精神病合并症的患者，和特定病因的获得性癫痫患者（卒中后癫痫/脑肿瘤相关癫痫/创伤性脑损伤相关癫痫）。这里,我们从关键试验和最近发表的日常临床实践证据中回顾了BRV的临床前概况和临床获益.
三分之一的癫痫患者尽管接受了治疗，但仍有癫痫发作。布立西坦是一种用于治疗癫痫患者癫痫发作的药物。它与大脑中的蛋白质（突触囊泡蛋白2A）结合，并在许多不同的癫痫动物模型中有效。布立西坦迅速进入大脑。它与其他药物几乎没有相互作用，这很重要，因为癫痫患者可能正在服用其他药物治疗癫痫或其他疾病。布立西坦可作为片剂，口服溶液，和静脉注射溶液，可以在推荐的目标剂量开始，并且易于使用。在三个III期试验中，每天服用布立西坦50~200mg的局灶性发作性癫痫发作不受控制的患者的癫痫发作少于服用安慰剂的患者.布立西坦耐受性良好。它在许多以前对抗癫痫药物没有反应的人中也很有效。布立西坦治疗的疗效可维持长达14年。布立西坦治疗可减少老年人（≥65岁）的癫痫发作，儿童（<16岁），在有认知或学习障碍的人中，在患有其他精神病的人身上，在患有不同原因的癫痫患者中（中风后癫痫，脑肿瘤相关癫痫,和创伤性脑损伤相关癫痫)。这里,我们回顾了布立拉西坦的特征和癫痫患者在关键临床试验和日常临床实践中的真实世界研究中接受布立拉西坦时的结果.
三分之一的癫痫患者尽管接受了治疗，但仍有癫痫发作。布立西坦是一种用于治疗癫痫患者癫痫发作的药物。它与大脑中的蛋白质（突触囊泡蛋白2A）结合，并在许多不同的癫痫动物模型中有效。布立西坦迅速进入大脑。它与其他药物几乎没有相互作用，这很重要，因为癫痫患者可能正在服用其他药物治疗癫痫或其他疾病。布立西坦可作为片剂，口服溶液，和静脉注射溶液，可以在推荐的目标剂量开始，并且易于使用。在三个III期试验中，每天服用布立西坦50~200mg的局灶性发作性癫痫发作不受控制的患者的癫痫发作少于服用安慰剂的患者.布立西坦耐受性良好。它在许多以前对抗癫痫药物没有反应的人中也很有效。布立西坦治疗的疗效可维持长达14年。布立西坦治疗可减少老年人（≥65岁）的癫痫发作，儿童（<16岁），在有认知或学习障碍的人中，在患有其他精神病的人身上，在患有不同原因的癫痫患者中（中风后癫痫，脑肿瘤相关癫痫,和创伤性脑损伤相关癫痫)。这里,我们回顾了布立拉西坦的特征和癫痫患者在关键临床试验和日常临床实践中的真实世界研究中接受布立拉西坦时的结果.
