UCB癫痫药物Brivarcetam III期显著改善癫痫发作

比利时制药巨头优时比（UCB）7月23日公布了癫痫药物brivaracetam（布瓦西坦）一项为期12周的III期研究的积极顶线数据。该项研究在768例伴有部分性发作（POS）但经1种或2种抗癫痫药物（AED）联合用药不能完全控制病情的局灶性癫痫（focal epilepsy）成人患者中开展，调查了brivaracetam（100和200mg/天）相对于安慰剂的疗效和安全性，研究中，将brivaracetam作为一种辅助药物用于患者的治疗。数据表明，与安慰剂相比，brivaracetam可显著降低部分性发作频率并改善反应率，2者均具有统计学显著差异。研究中brivaracetam耐受性与既往研究一致，最常见的不良反应包括嗜睡、头晕、乏力和头痛。该项研究的详细数据，将提交至未来的科学会议。
 
根据该研究的数据，UCB计划于2015年分别向FDA和欧洲药品管理局（EMA）提交brivaracetam的新药申请（NDA）和上市许可申请（MAA）。

如果获批，brivaracetam将成为UCB旗帜性癫痫专营权中的第3个上市产品。UCB公司最畅销的药物为Keppra，该药专利于2011年到期，在2013年的销售额已下跌15%至9.59亿美元。UCB的另一个产品Vimpat于2008年获批作为辅助药物，该药的销售在2013年增长23%至5.53亿美元，该公司正在开展后期研究，寻求批准该药用于儿科患者，同时作为成人患者的单药疗法。

UCB公司2015年即将上任的新首席，正密谋摆脱对中枢神经系统专营权的的依赖，寻求在免疫学领域建立一个新的生物制剂专营权，在该领域中，单抗药物Cimzia（certolizumab，赛妥珠单抗）已获批用于类风湿性关节炎、克罗恩病、银屑病关节炎的治疗，除此之外，UCB也正在开发狼疮、骨质疏松症及其他免疫疾病的药物。

brivaracetam为西坦类衍生物，具有广泛的抗癫痫活性和较高的安全性，该药可通过与突触囊泡蛋白2A(SV2A)结合而发挥抗癫痫作用。

英文原文：Major advance in UCB pipeline: positive topline Phase 3 results for brivaracetam in epilepsy patients with partial-onset seizures

•Brivaracetam is the newest investigational medicine to emerge from UCB’s rich late-stage pipeline

• Submissions to US and EU regulatory authorities planned for early 2015: subject to approval as adjunctive treatment for partial-onset seizures in adult epilepsy patients, brivaracetam would provide a new option for people with uncontrolled seizures

• Brivaracetam clinical development program has involved over 3,000 people and offers over 8 years of clinical experience with some patients1

Brussels (Belgium), 23rd July 2014 – 0700 (CEST) – regulated information – UCB today announced an important advance in its research and development pipeline with positive topline results from the latest Phase 3 study with brivaracetam. This study was designed to evaluate the efficacy and safety of brivaracetam (100 and 200 mg/day, without titration) compared to placebo, as adjunctive treatment in adult focal epilepsy patients with partial-onset seizures, not fully controlled despite treatment with one or two concomitant antiepileptic drugs (AEDs).2

Results showed that brivaracetam reduced partial-onset seizure frequency and improved responder rates, both with statistical significance. The most commonly reported adverse events were somnolence, dizziness, fatigue and headache.3

“Today’s positive results with brivaracetam represent a significant milestone in our strategy to deliver new treatment options for people with severe diseases. As the newest product to emerge from our late-stage pipeline, brivaracetam is leading the way for UCB’s new era of patient-centric solutions,” said Jean-Christophe Tellier, CEO-Elect, UCB. “We are proud to provide AED options for the epilepsy community today, and remain committed to addressing the unmet needs of adult patients who continue to experience uncontrolled seizures.”

“The positive data from the most recent Phase 3 study demonstrated robust and clinically relevant seizure reduction in predominantly treatment resistant patients, and tolerability was consistent with previous brivaracetam trials4-6,” said Professor Dr. Iris Loew Friedrich, Chief Medical Officer and Executive Vice President, UCB. “This study was the largest Phase 3 study conducted in epilepsy patients with partial-onset seizures. Overall, the brivaracetam development program has involved over 3,000 people and offers over eight years of clinical experience with some patients.1 We look forward to discussing the data with the regulatory authorities and the scientific community.”

Based on the results of the brivaracetam Phase 3 program, UCB plans to submit a New Drug Application to the US Food & Drug Administration (FDA) and a Marketing Authorization Application to the European Medicines Agency (EMA) in early 2015.

This Phase 3 study was a randomized, double-blind, placebo-controlled, multicentre, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam (100 and 200 mg/day) compared to placebo, over a 12-week treatment period, in 768 randomized focal epilepsy patients (aged 16 to 80 years) with partial-onset seizures, not fully controlled despite treatment with one or two concomitant AEDs.2,7 The primary endpoint for the European regulatory authorities is the 50% responder rate for partial-onset seizure frequency compared with placebo, over the treatment period standardized to a 28-day duration. The primary endpoint for the FDA is the percent reduction over placebo for partial-onset seizure frequency, over the treatment period standardized to a 28-day duration.2 Detailed data from this study will be submitted for presentation at upcoming epilepsy congresses and for publications in peer-reviewed journals.

About brivaracetam and the Phase 3 clinical development program
Discovered and developed by UCB, brivaracetam is a highly selective synaptic vesicle protein 2A ligand.8,9

The phase 3 clinical development plan for brivaracetam consisted of the following studies:

N01252: an evaluation of the efficacy and safety/tolerability of adjunctive brivaracetam 20, 50, and 100 mg/day compared with placebo over 12 weeks, in 399 randomized patients (16 to 70 years) with partial-onset seizures not fully controlled despite treatment with 1-2 concomitant AEDs.4

N01253: an evaluation of the efficacy and safety/tolerability of adjunctive brivaracetam at doses of 5, 20, and 50 mg/day compared with placebo over 12 weeks, in 400 randomized patients (16 to 70 years) with partial-onset seizures, not fully controlled despite treatment with 1-2 concomitant AEDs.5

N01254: an evaluation of the safety and tolerability of adjunctive brivaracetam given at individualized tailored doses between 20 and 150 mg/day, compared with placebo over 16 weeks, in 480 randomized patients (≥16 to 70 years) with uncontrolled epilepsy (up to 20% could be patients with generalized epilepsy), not fully controlled despite treatment with 1-3 concomitant AEDs.6

N01358: an evaluation of the efficacy and safety of adjunctive brivaracetam 100 and 200 mg/day compared with placebo over 12 weeks in 768 randomized patients (≥16 to 80 years) with partial-onset seizures, not fully controlled despite treatment with 1-2 concomitant AEDs.2,7

About Epilepsy10,11,12

Epilepsy is a chronic neurological disorder affecting approximately 65 million people worldwide. It is considered to be a disease of the brain defined by any of the following conditions: (1) at least two unprovoked (or reflex) seizures occurring >24 hours apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome.

Although epilepsy may be linked to factors such as health conditions, race and age, it can develop in anyone at any age, and approximately 1 in 26 people will develop epilepsy in their lifetime.

Partial seizures begin with an electrical discharge in one area of the brain. Different things can cause partial seizures, for example head injury, brain infection, stroke, tumour, and changes in the way an area of the brain was formed before birth, called cortical dysplasias. Many times, no known cause is found, but genetic factors may be important in some partial seizures

About UCB in Epilepsy

UCB has a rich heritage in epilepsy with over 20 years of experience in the research and development of antiepileptic drugs. As a company with a long-term commitment to epilepsy research our goal is to address unmet medical needs. Our scientists are proud to contribute to advances in the understanding of epilepsy and its treatment. We partner and create super-networks with world-leading scientists and clinicians in academic institutions, pharmaceutical companies and other organizations who share our goals. At UCB, we are inspired by patients and driven by science in our commitment to support patients with epilepsy.