Positive Top-Line Results From Pfizer’s Phase 3 JADE DARE Trial Comparing the Efficacy of Abrocitinib and Dupilumab for Moderate to Severe Atopic Dermatitis

辉瑞公司3期JADE DARE试验比较阿布替尼和杜匹卢单抗治疗中重度特应性皮炎疗效的阳性顶线结果

2021-08-30 21:00:12 BioSpace


JADE DARE trial met co-primary and key secondary endpoints and demonstrated a safety profile consistent with previous studies NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced that JADE DARE (B7451050), a 26-week, randomized, double-blind, double-dummy, active-controlled, multi-center Phase 3 study, met its co-primary and key secondary efficacy endpoints. The study showed that abrocitinib was statistically superior compared to dupilumab in each evaluated efficacy measure and had a safety profile consistent with previous studies. The head-to-head study was designed to directly compare the efficacy of abrocitinib 200mg versus dupilumab 300mg, in adult participants on background topical therapy with moderate to severe atopic dermatitis (AD). Abrocitinib 200mg was administered by once-daily oral tablet and dupilumab was administered by subcutaneous injection every other week following a 600mg induction dose. “The results from our first formal head-to-head trial for abrocitinib illustrate its potential for meaningful symptom relief for patients and further build upon the substantial body of data from the JADE development program,” said Michael Corbo, PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global Product Development. “We’re pleased that the study findings show the potential impact abrocitinib could have to help people living with moderate to severe atopic dermatitis in reducing their itch significantly and in achieving near complete skin clearance.” The co-primary efficacy endpoints in JADE DARE were the proportion of patients achieving at least a 4-point improvement in the severity of Peak Pruritus Numerical Rating Scale (PP-NRS4) from baseline at Week 2 and the proportion of patients achieving Eczema Area and Severity Index (EASI)-90 (≥90% improvement from baseline) at Week 4. The key secondary endpoint was the proportion of patients achieving EASI-90 at Week 16. The study will allow assessment of any difference in efficacy that may persist at month 6 of treatment. A larger percentage of patients treated with abrocitinib 200mg experienced adverse events compared to dupilumab 300mg. The proportion of patients experiencing serious adverse events, severe adverse events, and adverse events leading to study discontinuation were similar in both treatment arms. Two deaths occurred in patients treated with abrocitinib 200mg, which were characterized by the investigator as unrelated to the study drug. One death was attributed to COVID-19 and the second was attributed to intracranial hemorrhage and cardiorespiratory arrest, and classified as a major adverse cardiovascular event (MACE). There were no cases of malignancies or venous thromboembolism (VTE) events confirmed through adjudication. The safety profile seen with abrocitinib was consistent with previous studies in the JADE program. The study is part of the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global development program for abrocitinib. Full results from JADE DARE will be submitted for presentation at a future scientific meeting and publication in a medical journal. Additionally, at the appropriate time, Pfizer intends to share these data with the U.S. Food and Drug Administration (FDA) and other regulatory agencies around the world reviewing submissions for abrocitinib. About Abrocitinib Abrocitinib is an oral small molecule that selectively inhibits Janus kinase (JAK) 1. Inhibition of JAK1 is thought to modulate multiple cytokines involved in pathophysiology of atopic dermatitis, including interleukin IL-4, IL-13, IL-31, IL-22, and thymic stromal lymphopoietin (TSLP). About Atopic Dermatitis AD is a chronic skin disease characterized by inflammation of the skin and skin barrier defects.i,ii Lesions of AD are characterized by erythema (skin turning red or purple depending on normal skin color), itching, induration (hardening)/papulation (formulation of papules), and oozing/crusting.ii,iii AD is one of the most common, chronic, relapsing childhood dermatoses, affecting up to 10% of adults and up to 20% of children worldwide.iii,iv About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. Disclosure Notice The information contained in this release is as of August 30, 2021. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about a product candidate, abrocitinib, including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications may be filed in any other jurisdictions for any potential indication for abrocitinib; whether and when the applications for abrocitinib pending with the U.S. Food and Drug Administration and European Medicines Agency may be approved and whether and when any such other applications that may be pending or filed may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether abrocitinib will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of abrocitinib; uncertainties regarding the commercial or other impact of the results of Janus kinase (JAK) inhibitor studies and data and actions by regulatory authorities based on analysis of such studies and data, which will depend, in part, on benefit-risk assessments and labeling determinations; uncertainties regarding the impact of COVID-19 on our business, operations, and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com. i Hanifin JM, Reed ML. A population-based survey of eczema in the United States. Dermatitis. 2007;18(2):82-91. ii Bieber T. Atopic dermatitis. Dermatology. 2012;1(3):203-217. iii Oszukowska M, Michalak I, Gutfreund K, et al. Role of primary and secondary prevention in atopic dermatitis. Postep Derm Alergol. 2015:32(6):409-420. iv Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015;66(suppl 1):8-16. View source version on businesswire.com: https://www.businesswire.com/news/home/20210830005111/en/ Media Relations: Steve Danehy +1 (212) 733-1538 Steven.Danehy@pfizer.com Investor Relations: Christopher Stevo +1-212-733-0437 Christopher.stevo@pfizer.com Source: Pfizer Inc. View this news release online at: http://www.businesswire.com/news/home/20210830005111/en
JADE DARE试验满足了共主终点和关键次终点,并证明了与以前研究一致的安全性 纽约--(商业网)--辉瑞公司(纽约证券交易所代码:PFE)今天宣布,JADE DARE(B7451050)是一项为期26周的随机、双盲、双假人、主动对照、多中心3期研究,符合其共同主要疗效和关键次要疗效终点。该研究表明,与杜匹单抗相比,阿布西替尼在每项疗效评价指标上都有统计学上的优势,安全性概况与以前的研究一致。这项头对头的研究旨在直接比较阿布替尼200mg与杜比单抗300mg在背景局部治疗中重度特应性皮炎(AD)的成人参与者中的疗效。阿布西替尼200mg每日1次口服,杜匹卢单抗600mg诱导后每隔一周皮下注射一次。 辉瑞全球产品开发公司炎症和免疫学首席开发官迈克尔·科博博士说:“我们对abrocitinib的首次正式面对面试验的结果表明,它有可能为患者提供有意义的症状缓解,并进一步建立在JADE开发项目的大量数据基础上。”“我们很高兴研究发现表明,阿布洛替尼可能会帮助患有中度至重度特应性皮炎的人显著减轻瘙痒,并实现近乎完全的皮肤清除。” JADE DARE的共同主要疗效终点是:在第2周,峰值瘙痒数值评分(PP-NRS4)的严重程度比基线至少改善4点的患者比例;在第4周,湿疹面积和严重程度指数(EASI)-90(≥90%比基线改善)的患者比例。关键的次要终点是在第16周达到EASI-90的患者比例。这项研究将允许评估任何疗效差异可能持续到治疗的第6个月。 与杜匹卢单抗300mg相比,阿布西替尼200mg治疗的患者出现不良事件的比例更大。在两个治疗组中,经历严重不良事件、严重不良事件和导致研究中断的不良事件的患者比例相似。两例死亡发生在接受阿布替尼200mg治疗的患者中,研究者认为这两例死亡与研究药物无关。一例死亡归因于新冠肺炎,第二例归因于颅内出血和心肺骤停,并被归类为重大心血管不良事件(MACE)。没有通过裁决确认恶性肿瘤或静脉血栓栓塞(VTE)事件的病例。abrocitinib的安全性与以前JADE项目的研究一致。 这项研究是Abrocitinib的JAK1特应性皮炎疗效和安全性(JADE)全球开发项目的一部分。JADE DARE的全部结果将提交给未来的科学会议,并在医学杂志上发表。此外,辉瑞打算在适当的时候与美国食品药品监督管理局(FDA)和世界各地审查阿布洛西替尼提交的其他监管机构分享这些数据。 关于Abrocitinib Abrocitinib是一种选择性抑制Janus激酶(JAK)1的口服小分子。抑制JAK1被认为可以调节多种参与特应性皮炎病理生理的细胞因子,包括白细胞介素IL-4、IL-13、IL-31、IL-22和胸腺基质淋巴细胞生成素(TSLP)。 关于特应性皮炎 AD是一种以皮肤发炎和皮肤屏障缺陷为特征的慢性皮肤病。I、ii AD的病变以红斑(皮肤因正常肤色而变红或变紫)、瘙痒、硬结(硬化)/丘疹(丘疹形成)和渗出/结皮为特征 AD是一种最常见的慢性复发性儿童皮肤病,影响到世界上高达10%的成人和高达20%的儿童 关于辉瑞:改变患者生活的突破 在辉瑞,我们应用科学和我们的全球资源为人们带来治疗,延长并显著改善他们的生命。我们致力于为医疗保健产品的发现、开发和制造,包括创新药物和疫苗,制定质量、安全和价值标准。每天,辉瑞的同事们都在发达国家和新兴市场工作,以促进健康、预防、治疗和治愈,挑战我们时代最可怕的疾病。根据我们作为世界一流创新生物制药公司之一的责任,我们与卫生保健提供者、政府和当地社区合作,支持和扩大在世界各地获得可靠、负担得起的卫生保健的机会。170多年来,我们一直致力于为所有依赖我们的人做出改变。我们经常在我们的网站www.pfizer.com上发布对投资者可能重要的信息。此外,要了解更多信息,请访问我们www.pfizer.com,并在推特@辉瑞和@辉瑞新闻、LinkedIn、YouTube上关注我们,在脸书Facebook.com/pfizer上像我们一样关注我们。 披露通知 本发布包含的信息截至2021年8月30日。辉瑞不承担因新信息或未来事件或发展而更新本新闻稿中所包含的前瞻性陈述的义务。 本新闻稿包含关于候选产品abrocitinib的前瞻性信息,包括其潜在好处,其中涉及可能导致实际结果与这些声明所表达或暗示的结果大相径庭的重大风险和不确定性。风险和不确定因素包括,除其他外,研究和开发中固有的不确定因素,包括满足预期临床终点的能力、临床试验的开始和/或完成日期、监管提交日期、监管批准日期和/或启动日期,以及不利的新临床数据的可能性和对现有临床数据的进一步分析;临床试验数据受到监管当局不同解释和评估的风险;监管当局是否会对我们临床研究的设计和结果感到满意;是否以及何时可以在任何其他司法管辖区提出药物申请,以获得阿布西替尼的任何潜在适应症;abrocitinib在美国食品药品监督管理局和欧洲药品管理局的申请是否以及何时获得批准,监管当局是否以及何时批准任何其他可能正在等待或提交的申请,这将取决于无数因素,包括确定产品的益处是否超过其已知风险,确定产品的功效,以及如果获得批准,abrocitinib是否在商业上成功;监管当局对标签、制造工艺、安全和/或其他可能影响Abrocitinib可用性或商业潜力的事项的决定;Janus激酶(JAK)抑制剂研究结果和数据的商业或其他影响方面的不确定性以及监管当局根据对此类研究和数据的分析采取的行动,这将部分取决于收益-风险评估和标签确定;关于COVID-19对我们的业务、运营和财务业绩影响的不确定性;和竞争性发展。 关于风险和不确定性的进一步描述可参见辉瑞截至2020年12月31日的财年关于10-K表的年度报告及其随后关于10-Q表的报告,包括标题为“风险因素”和“可能影响未来结果的前瞻性信息和因素”的部分,以及随后关于8-K表的报告,所有这些报告都提交给美国证券交易委员会,并可在www.sec.gov和www.pfizer.com获得。 i Hanifin JM,Reed ML。美国湿疹的一项基于人群的调查。皮炎。2007年;18(2):82-91。 ii比伯T特应性皮炎。皮肤科。2012年;1(3):203-217。 iii Oszukowska M,Michalak I,Gutfreund K,et al.一级和二级预防在特应性皮炎中的作用。脚踏皮肤警报。2015年:32(6):409-420。 特应性皮炎:全球流行病学和危险因素。安努特尔梅塔布。2015;66(补编1):8-16。 在businesswire.com查看源代码版本:https://www.businesswire.com/news/home/20210830005111/en/ 媒体关系: 史蒂夫·达内希 +1(212)733-1538 @pfizer.com 投资者关系: 克里斯托弗·斯蒂沃 +1-212-733-0437 @pfizer.com 资料来源:辉瑞公司。 在网上查看此新闻稿: http://www.businesswire.com/news/home/20210830005111/en