Eisai and Imbrium Therapeutics Announce U.S. FDA Filing Acceptance of New Drug Application for Lemborexant for the Treatment of Insomnia

卫材与 Imbrium Therapeutics 的 lemborexant 新药申请已获 FDA 审查

2019-03-18 17:42:00 drugs

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lemborexant TOKYO and STAMFORD, Conn. – March 12, 2019 – Eisai Co., Ltd. (CEO: Haruo Naito, “Eisai”) and Imbrium Therapeutics L.P. (Imbrium Therapeutics), a clinical-stage biopharmaceutical company and operating subsidiary of Purdue Pharma, L.P. (President and CEO: Craig Landau, MD) today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for lemborexant, an investigational agent being studied for the treatment of insomnia, a sleep-wake disorder. A Prescription Drug User Fee Act (PDUFA) date is set for December 27, 2019. The NDA submission was based on data from the clinical development program including two pivotal Phase 3 studies of lemborexant – SUNRISE 1 (Study 304) and SUNRISE 2 (Study 303). “Our ultimate goal for the development of a sleep-wake treatment is to bring to patients living with insomnia a new option that has the potential to improve their ability to fall asleep, stay asleep and wake the next morning without impairment,” said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. “This milestone for lemborexant brings us one step closer to addressing unmet needs for millions of patients who experience insomnia.” “Insomnia, a disorder of sleep quality and quantity, causes significant impairment in daily functioning and has long-term consequences for health and well-being,”3 said John Renger, PhD, Vice President, Head of Research & Development and Regulatory Affairs, Imbrium Therapeutics. “We are committed to working with our partner Eisai to make this investigational treatment available to patients, pending regulatory approval.” Lemborexant is being jointly developed by Eisai and Imbrium Therapeutics for the treatment of multiple sleep-wake disorders, including insomnia disorder. Information about ongoing clinical studies is available at clinicaltrials.gov. Eisai and Imbrium Therapeutics are striving to address new unmet medical needs and to improve the lives of patients and their families. This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval. Lemborexant is a novel investigational small molecule compound, discovered and developed by Eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2). In individuals with normal daily sleep-wake rhythms, orexin signaling is believed to promote periods of wakefulness. In individuals with sleep-wake disorders, it is possible that orexin signaling that regulates wakefulness is not functioning normally, suggesting that inhibiting inappropriate orexin signaling may enable initiation and maintenance of sleep. Eisai and Imbrium Therapeutics are investigating lemborexant as a potential treatment option for multiple sleep-wake disorders, such as insomnia. Additionally, a Phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder (ISWRD) and mild to moderate Alzheimer's dementia is underway. SUNRISE 1 was a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group study evaluating the efficacy and safety of lemborexant in 1,006 male or female adult patients 55 years and older (45 percent of patients were 65 years and older) with insomnia disorder conducted in North America and Europe. SUNRISE 1 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a 30-day treatment period and a minimum two-week period without treatment prior to the end-of-study visit. In this study, patients were randomized to receive placebo or one of three treatment regimens (lemborexant 5 mg, lemborexant 10 mg, zolpidem ER 6.25 mg). The primary objective for SUNRISE 1 was to demonstrate using polysomnography that lemborexant at either the 5 mg or 10 mg dose is superior to placebo on objective sleep onset, as measured by latency to persistent sleep after the last two nights of one month of treatment. Key secondary objectives included change from baseline in sleep efficiency and wake after sleep onset (WASO) for both lemborexant doses compared to placebo, and WASO in the second half of the night (WASO2H) for both lemborexant doses compared to zolpidem ER, each after the last two nights of one month of treatment. SUNRISE 2 was a 12-month multicenter, global, randomized, controlled, double-blind, parallel-group study of the efficacy and safety of lemborexant in 949 male or female adult participants 18 to 88 years of age with insomnia disorder. SUNRISE 2 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a six-month placebo-controlled treatment period, a six-month period of active-only treatment and a two-week period without treatment prior to the end-of-study visit. In this study, during the placebo-controlled treatment period, patients were randomized to receive placebo or one of two treatment regimens (lemborexant 5 mg or 10 mg). During the active-only treatment period, patients who received placebo during the first period were re-randomized to receive lemborexant 5 mg or 10 mg. Patients who received active treatment during the first period continued on the treatment to which they were originally randomized. The primary objective was change from baseline in subjective sleep onset latency after six months of placebo-controlled treatment using patient reported (subjective) sleep diaries. Key secondary endpoints were change from baseline in subjective sleep efficiency and subjective wake after sleep onset (sWASO) by using patient reported (subjective) sleep diaries for both lemborexant doses after six months of placebo-controlled treatment. Population studies show that sleep disorders affect many more people worldwide than previously thought.4 Insomnia disorder is the most common sleep disorder affecting approximately 30 percent of the adult population worldwide.4,5 Insomnia disorder is characterized by difficulty falling asleep, staying asleep or both, despite an adequate opportunity to sleep, which can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.3,6 Sleeping well is essential for good health, including brain health. Poor sleep is associated with a wide range of health consequences, including an increased risk of hypertension, accidental injury, diabetes, obesity, depression, heart attack, stroke and dementia, as well as adverse effects on mood and behavior.3,7 Experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases and mortality.8 Studies suggest an optimal sleep duration between seven and eight hours.9 Women are 1.4 times more likely than men to suffer from insomnia.10 Older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent waking and early waking, that can lead to less sleep time.
柠檬黄 康涅狄格州东京和斯坦福。-2019年3月12日- Eisai Co ., Ltd .( CEO : Haruo Naito ,“卫材(Eisai)”)和 Imbrium Therapeutics L.P .( Imbrium Therapeutics ), Purdue Pharma 的临床阶段生物制药公司和运营子公司, L.P .(总裁兼首席执行官: Craig Landau )美国食品药品监督管理局(Food and Drug Administration)( FDA )今天宣布,已经接受了对柠檬黄的新药申请( NDA )的审查。柠檬黄是一种正在研究的用于治疗失眠和睡眠觉醒障碍的研究药物。处方药用户费法( PDUFA )日期为2019年12月27日。 NDA 的提交是基于临床开发计划的数据,包括两个关键的柠檬黄3期研究—— SUNRISE 1(研究304)和 SUNRISE 2(研究303)。 Eisai Neurology Business Group 首席临床官兼首席医务官 Lynn Kramer 医学博士表示:“我们开发睡眠-觉醒治疗的最终目标是为失眠患者带来一种新的选择,它有可能提高患者入睡、入睡和第二天早上醒来的能力,而不会受到损害。”“莱姆贝拉克特的这一里程碑使我们更接近解决数百万失眠患者未得到满足的需求。” Imbrium Therapeutics 研究与开发及监管事务副总裁 John Renger 博士表示:“失眠是一种睡眠质量和数量的紊乱,会导致日常运作严重受损,并对健康和福祉造成长期影响。”“我们致力于与我们的合作伙伴卫材(Eisai)合作,在获得监管批准之前,将这项研究治疗提供给患者。” Lembrexant 由卫材(Eisai)和 Imbrium Therapeutics 联合开发,用于治疗包括失眠在内的多种睡眠-觉醒障碍。有关正在进行的临床研究的信息可在临床试验。政府。 卫材(Eisai)和 Imbrium Therapeutics 正在努力解决新的未得到满足的医疗需求,改善患者及其家属的生活。 本新闻稿讨论了一种药物在开发中的研究用途,并不旨在传达有关疗效或安全性的结论。不能保证这种研究代理人将成功完成临床开发或获得卫生当局的批准。 Lemborexant 是一种新型的研究小分子化合物,由卫材(Eisai)的内部科学家发现和开发,通过与奥里欣受体亚型(奥里欣受体1和2)竞争结合抑制奥里欣信号。在有正常的日常睡眠-觉醒节律的个体中, orexin 信号被认为促进了清醒时期。在患有睡眠-觉醒障碍的个体中,调节清醒的 orexin 信号可能不能正常发挥作用,这表明抑制不适当的 orexin 信号可能导致睡眠的启动和维持。卫材(Eisai)和 Imbrium Therapeutics 公司正在调查莱姆贝拉克特作为一种潜在的治疗多种睡眠-觉醒障碍的选择,如失眠。此外,一项第二期临床研究的柠檬黄在不规则睡眠-觉醒节律障碍( ISWRD )和轻度至中度阿尔茨海默症患者正在进行。 SUNRISE1是一项多中心、随机、双盲、安慰剂对照、积极对照、平行对照的研究,评估了1,006名男性或女性成人患者55岁及以上(45%的患者65岁及以上)的疗效和安全性。SUNRISE 1包括最多35天的随机化前阶段(包括为期两周的安慰剂期)和随机化阶段,包括30天的治疗期和至少两周的没有治疗前结束访问。在这项研究中,患者随机接受安慰剂或三种治疗方案中的一种(柠檬黄5mg ,柠檬黄10mg ,唑吡坦 ER 6.25mg )。 SUNRISE1的主要目的是通过多导睡眠图证明,在5毫克或10毫克剂量的柠檬黄在客观睡眠发作时优于安慰剂,这是通过治疗后最后两个月的晚后持续睡眠的潜伏期来衡量的。主要的次要目标包括:与安慰剂相比,服用柠檬黄素剂量的睡眠效率和睡眠后醒来( WASO )的基线变化;服用两种柠檬黄素剂量的 WASO 在治疗后的最后两个晚上一个月后,在治疗后的后半夜( WASO _2H )的变化。 SUNRISE 2是一项为期12个月的多中心、全球、随机、对照、双盲、平行分组的研究,研究了柠檬黄在949名男性或女性成人参与者中的疗效和安全性,年龄在18至88岁之间。SUNRISE 2包括最多35天的随机化前阶段(包括两周的安慰剂周期)和随机化阶段,包括6个月的安慰剂对照治疗期间、6个月的仅活动治疗期间和两周的无治疗期间。在本研究中,在安慰剂对照治疗期间,患者随机接受安慰剂或两种治疗方案中的一种(柠檬烯5mg 或10mg )。在主动治疗期间,在第一期接受安慰剂的患者被重新随机接受5毫克或10毫克的柠檬黄。第一期接受积极治疗的患者继续接受他们最初随机接受的治疗。 主要的目的是改变基线的主观睡眠开始潜伏期后6个月安慰剂对照治疗使用患者报告(主观)睡眠日记。主要的次要终点是在六个月的安慰剂对照治疗后,使用患者报告的(主观的)睡眠日记对两种柠檬黄剂量的主观睡眠效率和睡眠后主观觉醒的基线变化。 人口研究表明,睡眠障碍影响的人比以前想象的更多。失眠是最常见的睡眠障碍,影响了全世界约30%的成年人。4,5失眠的特点是难以入睡、入睡或两者兼而有之,尽管有充足的睡眠机会,这可能导致白天疲劳、注意力不集中和易怒等后果。3,6 睡眠良好对于良好的健康是必不可少的,包括大脑健康。睡眠不足与一系列健康后果有关,包括高血压、意外伤害、糖尿病、肥胖、抑郁症、心脏病、中风和痴呆的风险增加,以及对情绪和行为的不利影响。3,7 动物和人类的实验研究提供了睡眠和疾病风险因素、疾病和死亡率之间的联系的证据。8研究表明睡眠时间在7到8小时之间是最佳的。9 女性患失眠的几率是男性的1.4倍。10岁以上的成年人也有较高的失眠患病率;老龄化往往伴随着睡眠模式的变化,包括睡眠中断、频繁醒来和早起,这可能导致睡眠时间减少。

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