FDA Approves Motegrity (prucalopride) for Adults with Chronic Idiopathic Constipation (CIC)

Shire公司便秘药物 Motegrity 获 FDA 批准,在美预计有3500万成人市场

2018-12-18 09:28:48 drugs

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FDA Approves Motegrity (prucalopride) for Adults with Chronic Idiopathic Constipation (CIC) Cambridge, Mass. Shire plc (LSE: SHP, NASDAQ: SHPG) has announced that the U.S. Food and Drug Administration (FDA) has approved Motegrity™ (prucalopride), a once-daily, oral treatment option for adults with Chronic Idiopathic Constipation (CIC).1 Motegrity, a selective serotonin-4 (5-HT4) receptor agonist, provides a different class of treatment for CIC that works by enhancing colonic peristalsis to increase bowel motility.1-3 Motegrity is expected to launch in 2019 in the United States, where an estimated 35 million adults are living with CIC.4,5* While not all patients may be right for treatment, Motegrity represents an important new option. “The approval of Motegrity marks a new day in the treatment of CIC,” said Howard Mayer, M.D., Senior Vice President and Chief Medical Officer, Shire. “This significant milestone reinforces our continued commitment to the GI community and advances our goal of addressing the unmet need of patients suffering from rare, specialized and common GI conditions.” The efficacy of once-daily treatment with Motegrity was evaluated in six double-blind, placebo-controlled, randomized, multicenter clinical studies lasting 12 weeks (studies 1-5) or 24 weeks (study 6).1 Of the 2,484 patients, most were female (76%) and Caucasian (76%), with an average age of 47 (+/- 16 years).1 “As a gastroenterologist, it’s important for me to help patients with CIC find a treatment that works well for them,” said Brooks Cash, M.D., Chief of the Division of Gastroenterology, Hepatology, and Nutrition at the University of Texas Health Science Center at Houston. “It’s exciting to be able to now offer my patients a new treatment option that addresses colonic peristalsis.” During studies, significantly more patients taking Motegrity achieved the primary endpoint (an average of ≥3 complete spontaneous bowel movements [CSBMs] per week over 12 weeks, considered normalization of BM frequency) than those in the placebo group (19-38% Motegrity ≤2 mg vs. 10-20% placebo) across five of six trials. A rapid response was seen with Motegrity as early as week 1, with improvements maintained throughout 12 weeks of treatment.1 The FDA has requested that Shire conduct five post-marketing studies evaluating the pharmacokinetics, efficacy, and safety of Motegrity in pediatric patients with CIC (6 months old to less than 18 years of age) and pregnant and lactating women with CIC treated with Motegrity.6 Motegrity is contraindicated in patients with a history of hypersensitivity to Motegrity. Reactions include dyspnea, rash, pruritus, urticaria, and facial edema have been observed. Motegrity is also contraindicated in patients with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn’s disease, ulcerative colitis, and toxic megacolon/megarectum.1 In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established. Monitor all patients treated with Motegrity for persistent worsening of depression or the emergence of suicidal thoughts and behaviors. Counsel patients, their caregivers, and family members of patients to be aware of any unusual changes in mood or behavior and alert the healthcare provider. Instruct patients to discontinue Motegrity immediately and contact their healthcare provider if they experience any of these symptoms.1 Most common adverse reactions (≥2%) are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence and fatigue.1 Overall, discontinuation due to adverse events was low (5% Motegrity 2 mg once daily; 3% placebo). If reported, adverse events of diarrhea or headache typically resolved within a few days.1 In addition, cardiovascular safety was evaluated in a MACE† (major adverse cardiovascular events) analysis of the double-blind, placebo-controlled and open-label studies. It was also assessed in a retrospective observational study, which demonstrated no increase in the risk of MACE† with Motegrity relative to polyethylene glycol (PEG).1 CIC is a common condition affecting roughly 14% of the adult population.4,5 Symptoms can range from straining and bloating, to infrequent, or incomplete bowel movements.7 While “idiopathic” by definition (meaning the exact cause is not known), it is believed that CIC may be caused by insufficient movement of the colon muscle.7 Important Safety Information Contraindications Motegrity is contraindicated in patients with: Warnings and Precautions In clinical trials, suicides, suicide attempts, and suicidal ideation have been reported. A causal association between treatment with Motegrity and an increased risk of suicidal ideation and behavior has not been established. Monitor all patients treated with Motegrity for persistent worsening of depression or the emergence of suicidal thoughts and behaviors. Counsel patients, their caregivers, and family members of patients to be aware of any unusual changes in mood or behavior and alert the healthcare provider. Instruct patients to discontinue Motegrity immediately and contact their healthcare provider if they experience any of these symptoms. Adverse Reactions Most common adverse reactions (≥2%) are headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence and fatigue.1 Overall, discontinuation due to adverse events was low (5% Motegrity 2 mg once daily; 3% placebo). If reported, adverse events of diarrhea or headache typically resolved within a few days.1 In addition, cardiovascular safety was evaluated in a MACE† (major adverse cardiovascular events) analysis of the double-blind, placebo-controlled and open-label studies. It was also assessed in a retrospective observational study, which demonstrated no increase in the risk of MACE† with Motegrity relative to polyethylene glycol (PEG).1 Use in Specific Populations Shire is the global biotechnology leader serving patients with rare diseases and specialized conditions. We seek to push boundaries through discovering and delivering new possibilities for patient communities who often have few or no other champions. Relentlessly on the edge of what’s next, we are serial innovators with a diverse pipeline offering fresh thinking and new hope. Serving patients and partnering with healthcare communities in over 100 countries, we strive to be part of the entire patient journey to enable earlier diagnosis, raise standards of care, accelerate access to treatment, and support patients. Our diverse portfolio of therapeutic areas includes Immunology, Hematology, Genetic Diseases, Neuroscience, Internal Medicine, and Ophthalmics. Championing patients is our call to action - it brings the opportunity - and responsibility - to change people’s lives. www.shire.com Forward-Looking Statements Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, projected revenues, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following: Shire’s products may not be a commercial success; increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire’s future revenues, financial condition and results of operations; Shire depends on third parties to supply certain inputs and services critical to its operations including certain inputs, services and ingredients critical to its manufacturing processes. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time; the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches; the nature of producing plasma-based therapies may prevent Shire from timely responding to market forces and effectively managing its production capacity; Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval; the actions of certain customers could affect Shire’s ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial conditions or results of operations; failure to comply with laws and regulations governing the sales and marketing of its products could materially impact Shire’s revenues and profitability; Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics; Shire’s patented products are subject to significant competition from generics; adverse outcomes in legal matters, tax audits and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on Shire’s revenues, financial condition or results of operations; Shire may fail to obtain, maintain, enforce or defend the intellectual property rights required to conduct its business; Shire faces intense competition for highly qualified personnel from other companies and organizations; failure to successfully execute or attain strategic objectives from Shire’s acquisitions and growth strategy may adversely affect Shire’s financial condition and results of operations; Shire’s growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products; a slowdown of global economic growth, or economic instability of countries in which Shire does business, could have negative consequences for Shire’s business and increase the risk of non-payment by Shire’s customers; changes in foreign currency exchange rates and interest rates could have a material adverse effect on Shire’s operating results and liquidity; Shire is subject to evolving and complex tax laws, which may result in additional liabilities that may adversely affect Shire’s financial condition or results of operations; if a marketed product fails to work effectively or causes adverse side effects, this could result in damage to Shire’s reputation, the withdrawal of the product and legal action against Shire; Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire’s revenues, financial condition or results of operations; Shire faces risks relating to the expected exit of the United Kingdom from the European Union; Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs and may decrease its business flexibility; the potential uncertainty among our employees, customers, suppliers, and other business partners resulting from the announcement by Takeda Pharmaceutical Company Limited on May 8, 2018 of a recommended offer for Shire under the UK Takeover Code; and a further list and description of risks, uncertainties and other matters can be found in Shire’s most recent Annual Report on Form 10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in “ITEM1A: Risk Factors”, and in Shire’s subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire’s website.
Shire plc ( LSE : SHP , NASDAQ : SHPG )宣布,美国食品和药物管理局( FDA )已批准 Motegrity ™(普瑞巴林),这是一种针对成人慢性特发性便秘(CIC)的每日一次口服治疗方案。 Motegrity是一种选择性血清素-4(5-HT4)受体激动剂,它为 CIC 提供了一种不同的治疗方法,即通过增强结肠蠕动来增加肠道运动。Motegrity 预计将于2019年在美国推出,彼时将会约有3500万成年人患有CIC。虽然并非所有患者都适合接受这种治疗,但Motegrity是一个重要的新选择。 Shire 高级副总裁兼首席医疗官 Howard Mayer 医学博士说:“批准 Motegrity 标志着CIC治疗的新时代。”“这一重要里程碑增进了我们对肠胃病患者群体持续的承诺,并推进了我们目标的进展,即满足那些患有罕见、特殊和常见肠胃病患者的未得到满足的需求。” 每日一次的Motegrity药物的疗效在6项双盲、安慰剂对照、随机、多中心临床研究中进行评估,持续12周(研究1-5)或24周(研究6)。在2484名患者中,大多数是女性(76%)和高加索人(76%),平均年龄为47岁(+/-16岁)。 “作为一名胃肠病学家,我必须帮助CIC病人找到一种有效的治疗方法,”休斯顿德克萨斯大学健康科学中心胃肠病学、肝脏病学和营养科主任 Brooks Cash 医学博士说。“能够为我的病人提供一种新的治疗方案,解决结肠蠕动的问题,是一件令人兴奋的事。” 在研究中,服用 Motegrity 的患者在12周内每周平均完成≥3次完全自发的肠道运动(被认为是 BM 频率的正常化),比安慰剂组(19-38% Motegrity ≤2 mg vs.10-20%安慰剂)的患者在6个试验中的5个试验中达到的次数更多。Motegrity在第一周就显示出快速的反应,在治疗的12周内持续改善病情。FDA 已要求 Shire 开展五项上市后研究,评估 CIC 患儿(6个月至18岁)和 CIC 治疗的孕妇和哺乳期妇女的药物动力学、疗效和安全性。 对Motegrity高度敏感的病人禁忌使用该药物。过敏反应包括呼吸困难、皮疹、瘙痒、荨麻疹和面部水肿。由于肠壁结构或功能障碍、梗阻性肠梗阻、严重的肠道炎症如克罗恩病、溃疡性结肠炎和毒性巨结肠/巨结肠,而患有肠道穿孔或梗阻的患者也禁忌使用该药物。 在临床试验中,自杀,自杀企图和自杀念头也被报道。Motegrity治疗以及自杀念头和自杀行为的增加之间的因果关系尚未确定。应监测所有接受 Motegrity 治疗的患者持续抑郁恶化或自杀念头和行为的出现。病人法律顾问,看护人员和病人的家庭成员发现任何异常的情绪或行为变化时,应提醒医护人员。一旦患者出现任何以上症状,应指导患者立即停止使用Motegrity,并联系他们的医护人员,。 最常见的不良反应(≥2%)为头痛、腹痛、恶心、腹泻、腹胀、头晕、呕吐、胀气和疲劳。总体而言,因不良反应而中断治疗的发生率较低(5% Motegrity2mg 每日一次;3%安慰剂)。如果有相关情况,腹泻或头痛等不良反应通常会在几天内得到解决。此外,对双盲、安慰剂对照和开放标签研究进行 MACE †(主要不良心血管事件)分析,评价心血管安全性。在一项回顾性观察研究中也对其进行了评估,结果表明,与聚乙二醇( PEG )相比, MACE† 与 Motegrity 的风险没有增加。 CIC 是一种常见的病症,影响了大约14%的成年人。症状包括肠道紧缩、胀气到不常见或不完全的肠道运动。虽然定义上的“特发性”指的是确切的病因尚不清楚,但一般认为是因结肠肌肉运动不足造成的。 重要安全资料 对比适应症 运动障碍在以下患者中是禁忌的: 警告及预防措施 在临床试验中,自杀,自杀企图和自杀念头被报道。治疗与 Motegrity 之间的因果关系以及自杀念头和行为增加的风险尚未确定。 监测所有接受 Motegrity 治疗的患者持续抑郁恶化或自杀念头和行为的出现。法律顾问病人,他们的照顾者和病人的家庭成员知道任何异常的情绪或行为变化,并提醒医疗保健提供者。指导患者立即停止运动,并联系他们的医疗保健提供者,如果他们有任何这些症状。 不良反应 最常见的不良反应(≥2%)为头痛、腹痛、恶心、腹泻、腹胀、头晕、呕吐、胀气和疲劳。1总体而言,因不良事件而中断的发生率较低(5% Motegrity2mg 每日一次;3%安慰剂)。如果有报道,腹泻或头痛的不良事件通常会在几天内得到解决。1此外,对双盲、安慰剂对照和开放标签研究进行 MACE △(主要不良心血管事件)分析,评价心血管安全性。在一项回顾性观察研究中也对其进行了评估,结果表明,与聚乙二醇( PEG )相比, MACE ∑与 Motegrity 的风险没有增加。 特定人群的使用 Shire 是全球生物技术的领导者,为罕见疾病和特殊情况的患者提供服务。我们致力于通过发现和提供新的可能性,支持通常选择有限或没有选择的患者群体。在下一阶段来临前,我们是连续不断的创新者,拥有一条多元化的通道,提供新思维和新希望。我们为患者提供服务,并与100多个国家的医疗保健社区合作,我们努力成为患者的整个康复之旅的一部分,以实现早期诊断,提高护理标准,加速治疗获取,并支持患者。我们多元化的治疗领域包括免疫学,血液学,遗传病,神经科学,内科和眼科。 支持病人是我们的行动号召,它带来了改变人们生活的机会和责任。 www.shire.com 前瞻性陈述 此处包含的并非历史事实陈述,包括但不限于关于未来战略、计划、目标、预期和意图、预计收入、临床试验和批准的预期时间以及内联或管道产品的商业潜力的陈述,均为前瞻性陈述。该等前瞻性陈述涉及多项风险及不明朗因素,并随时可能变动。如果出现此类风险或不确定性, Shire 的业绩可能受到重大不利影响。风险和不确定性包括但不限于以下内容: Shire 的产品不能保证取得商业成功。 政府法规和市场发展导致的定价压力和患者准入限制增加,可能影响 Shire 的未来收入、财务状况和经营业绩; Shire 依靠第三方提供对其运营至关重要的某些投入和服务,包括对其制造工艺至关重要的某些投入、服务和成分。任何 Shire 产品供应链的任何中断都可能导致 Shire 无法继续营销或开发产品,或可能导致 Shire 在一段时间内无法在商业可行的基础上运营; Shire 产品的制造受到各种监管机构的广泛监督。与制造场所、成分或制造过程的变更相关的监管批准或干预措施可能导致(其中包括)重大延迟、运营成本增加、产品销售损失、研究活动中断或新产品上市延迟; 生产基于血浆的疗法可能会阻止 Shire 及时响应市场力量并有效管理其生产能力; Shire 的产品组合处于不同的研发阶段。该等产品的成功开发具有高度的不确定性,需要大量的支出和时间,不保证该等产品获得监管部门的批准; 某些客户的行为可能会影响 Shire 销售或盈利销售产品的能力。此类客户购买或分销模式的波动可能对 Shire 的收入、财务状况或经营业绩产生不利影响; 未能遵守管辖其产品销售和营销的法律法规可能对 Shire 的收入和盈利能力产生重大影响; Shire 公司的产品和产品候选人在其经营的产品市场面临实质性竞争,包括来自仿制药的竞争; Shire 公司的专利产品与仿制药存在重大竞争; 法律事务、税务审计和其他纠纷的不利结果,包括 Shire 执行和保护其业务所需专利和其他知识产权的能力,可能对 Shire 的收入、财务状况或经营成果产生重大不利影响; Shire 可能无法获得、维护、执行或捍卫开展业务所需的知识产权; Shire 面临来自其他公司和组织的高素质人员的激烈竞争; 未能成功执行或实现 Shire 收购和增长战略的战略目标,可能对 Shire 的财务状况和经营成果产生不利影响; Shire 的增长战略部分取决于其通过外部合作扩大产品组合的能力,如果不成功,可能对其产品的开发和销售产生不利影响; 全球经济增长放缓,或 Shire 开展业务的国家经济不稳定,可能对 Shire 的业务产生负面影响,增加 Shire 客户不付款的风险; 外币汇率和利率的变化可能对 Shire 的经营业绩和流动性产生重大不利影响; Shire 须遵守不断变化和复杂的税法,这可能导致额外的负债,可能对 Shire 的财务状况或经营业绩产生不利影响; 如果营销产品不能有效工作或造成不良副作用,则可能导致 Shire 声誉受损、产品撤回以及对 Shire 的法律诉讼; Shire 依赖信息技术,其系统和基础设施面临某些风险,包括服务中断、敏感或机密信息丢失、网络攻击和其他可能对 Shire 收入、财务状况或运营结果产生重大不利影响的安全漏洞或数据泄露; Shire 面临英国退欧的相关风险; Shire 为收购 Baxalta 而产生大量额外债务,这增加了其借贷成本,并可能降低其业务灵活性; Takeda Pharmaceutical Company Limited 于2018年5月8日根据英国收购守则向 Shire 发出建议收购要约而导致雇员、客户、供应商及其他业务伙伴之间潜在的不确定性; 有关风险、不确定性和其他事项的进一步列举和描述,请参见 Shire 最近的10-K 年度报告表和 Shire 随后的10-Q 季度报告表,在每种情况下,“ ITEM1A :风险因素”中概述的风险都包含在内。以及 Shire 随后在8-K 表格和其他证券交易委员会备案文件中的报告,所有文件都可在 Shire 的网站上查阅。

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