Omalizumab

最近两年，自身免疫疾病药物的开发炙手可热，而其背后真正的原因还是要归咎于自免足够大的市场，根据沙利文报告显示，全球各类自免疾病患者规模近5亿人，2022年该领域药物市场规模约达1323亿美元，预计到2030年将达到1760亿美元。而且在该领域，爆款药品不断出现，先是Humira，后有Dupixent。随着2024年第二季度的财报披露，该领域单季度销售超过10亿美金的药物也先后出现，根据统计，该领域目前有10款药物单季度销售额超过或者接近10亿，其中9款是大分子，一款小分子。艾伯维占据3款，强生两款，诺华两款。 1 Dupixent (IL4/IL13 mAb) Dupixent是由赛诺菲和再生元联合开发的靶向白细胞介素-4（IL-4）和白细胞介素-13（IL-13）共享的受体亚基α（IL-4Rα）的单克隆抗体，自2017年3月28日获得美国FDA批准上市以来，Dupixent已经在全球多个国家获批用于治疗：1）中至重度特应性皮炎（AD）：适用于6个月及以上的患者，尤其是当外用药物无法有效控制症状或不适用时；2)中度至重度结节性痒疹（PN）：适用于成人患者，特别是那些需要系统治疗的情况;3)哮喘：适用于12岁及以上的青少年和成人，特别是那些使用中到高剂量吸入性糖皮质激素（ICS）和其他哮喘控制药物后仍然控制不佳的患者，以及那些依赖口服糖皮质激素的哮喘患者。 Dupixent2023年的销售额到达115.7亿美元，而且2024年预计将达到130亿欧元（约合140亿美元），根据赛诺菲第二季度的财报公布，Dupixent 2024Q2的销售额为33亿欧元，与2023三年同期相比，增加了29%，而对于前两个季度的销售，2024的已经达到了61亿欧元，与去年同期相比增加了约26%。从目前的销售额来看，Dupixent很有可能到达130亿欧元。 除了已经获批的适应症，COPD适应症在今年已经在欧盟获批，而且预计今年9月份也将会在US会批，这是十多年来欧盟首个针对COPD批准的新治疗方法，也是首个针对COPD患者获批的靶向治疗药物。根据Frost & Sullivan 统计，2019 年全球COPD 患者基数约4.57亿人，预计2024 年约5.28亿人，2019-2024 CAGR 约3.0%；2019 年国内COPD 患者数量约1.04亿人，预计2024 年患者基数约1.08 亿人。 关于其它适应症， 青少年鼻息肉慢性鼻窦炎已经在美国申报；儿童嗜酸性粒细胞性食管炎适应症已经在欧盟申报；大疱性类天疱疮和 慢性自发性荨麻疹已经位于临床三期。 2 Stelara（ustekinumab/喜达诺） Stelara（通用名：ustekinumab，中文商品名：喜达诺）是一种由强生公司（JNJ）旗下的杨森制药开发并生产的生物制剂，用于治疗多种免疫介导的炎症性疾病。它是一种选择性靶向IL-12和IL-23的生物制剂，通过与这两种细胞因子共有的p40亚基结合，阻止它们与细胞表面受体IL-12 β1结合，从而抑制炎症反应。2009年9月上市以来Stelara已经获批用于治疗以下疾病：1）中度至重度斑块型银屑病（PsO）的儿科患者（6-11岁）和青少年及成人患者（≥12岁）；2）成人活动性银屑病关节炎；3）成人中重度克罗恩病（CD）；4）成人中重度活动性溃疡性结肠炎（UC）。 Stelara的给药方式是通过皮下注射，起始剂量后，通常每年给药4次。在中国，Stelara（喜达诺®）于2019年6月上市，用于治疗对其他系统治疗不应答、有禁忌或无法耐受的成年中重度斑块状银屑病患者。 根据强生Q2财报披露，Stelara第二季度销售额为28.9亿美元，但是其美国专利已于2023年9月到期，后续肯定会面临生物类似药的激烈竞争。 3 曾经的药王Humira Humira（阿达木单抗）是由艾伯维（AbbVie）开发的治疗多种炎症性疾病的单克隆抗体。它在全球范围内获批用于治疗包括类风湿性关节炎、强直性脊柱炎、银屑病、克罗恩病等在内的多种疾病。 Humira作为全球最畅销的药物之一，其销售额在2022年达到了212.4亿美元的最高峰，成为当之无愧的“药王”。然而，随着2023年其在美国的专利保护到期，Humira将面临生物类似药的竞争。在欧洲，Humira已经开始与生物类似药竞争，这对其销售额产生了一定影响。 根据艾伯维Q2的财报披露，Humira Q2的销售额为28.1亿美元，与2023年同期相比，销售额下降了29.8%。在看前两个季度，其总销售额为50.8亿美元，同比下降32.7%，按照这个趋势，2024年Humira的销售额可能勉强能够站上100亿美元，看来类似药对其冲击还是比较大的。 4 Skyrizi（Risankizumab） Skyrizi同样是由艾伯维开发的单抗药物，该抗体靶向IL-23的p19亚基，从而选择性阻断体内免疫炎性介质白细胞介素-23（IL-23）介导的相关炎症。IL-23是一种参与炎症过程的细胞因子，被认为与多种慢性免疫介导的疾病有关。该药物自从2019年获批后，已经先后有多个适应症获批：1）中度至重度斑块状银屑病（Psoriasis） ；2）活动性银屑病关节炎（Psoriatic Arthritis, PsA）；3）中度至重度克罗恩病（Crohn's Disease, CD）；4）中度至重度溃疡性结肠炎（Ulcerative Colitis, UC）。 根据艾伯维Q2财报披露， Skyrizi第二季度的销售额接近27.3亿美元，与2023年同期相比，增加44.8%，而且其前半年销售额为47.35亿美元，直追Humira，与去年前半年相比，增幅达到46%。根据相关机构预处，Skyrizi2024年的销售额将会接近100亿美元，该药物将有力的补充Humira专利到期带来的冲击。 5 Cosentyx（secukinumab/可善挺） Cosentyx是由诺华开发的靶向IL-17A的单克隆抗体，其主要是通过抑制白细胞介素-17A（IL-17A）的活性来减少炎症和相关症状。Cosentyx已经有多个适应症获批：1）中度至重度斑块状银屑病（Psoriasis）；2）银屑病关节炎（Psoriatic Arthritis, PsA）；3）强直性脊柱炎（Ankylosing Spondylitis, AS）；4）放射学阴性中轴型脊柱关节炎（Non-radiographic axial spondyloarthritis, nr-axSpA）；5）化脓性汗腺炎（Hidradenitis Suppurativa, HS）；6）幼年特发性关节炎（Juvenile Idiopathic Arthritis, JIA）。 根据诺华财报显示，Cosentyx第二季度的销售额达到15.26亿美元，该药物无论在美国还是美国之外的市场都表现出强劲的增长势头，与2023年同期相比，增加了22%。 6 Entyvio（vedolizumab/安吉优） Entyvio（通用名：vedolizumab，商品名：安吉优）是由武田开发的靶向整合素α4β7单抗，被批准用于治疗对传统治疗手段或抗肿瘤坏死因子治疗疗效不足或已经耐受的成人中度至重度活动性溃疡性结肠炎(UC)和克罗恩病(CD)等适应症。其通过特异性拮抗α4β7整合素，抑制其与肠道黏膜细胞粘附分子MAdCAM-1的结合，从而减少炎症细胞向肠道炎症部位的迁移。 在国内，Entyvio已获得国家药品监督管理局（NMPA）的批准，用于治疗对传统治疗或TNFα抑制剂应答不充分、失应答或不耐受的中重度活动性UC和CD成人患者。 虽然武田第二季度财报还美元披露，但是根据相关机构预处，Entyvio第二季度的销售额接近15亿美元左右，而且根据其第一季度披露，Entyvio同比增长了7.6%。 7 Xolair（奥马珠单抗） Xolair（奥马珠单抗）是一种靶向免疫球蛋白E（IgE）的重组人源化单克隆抗体，由罗氏（Roche）和诺华（Novartis）共同开发和销售。它主要用于治疗中度至重度持续性过敏性哮喘、慢性特发性荨麻疹（CIU）和慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）等过敏性疾病。 IgE是一种在过敏反应中起关键作用的抗体，它能够与体内的肥大细胞和嗜碱性粒细胞表面的高亲和力IgE受体（FcεRI）结合，当IgE与过敏原结合后，会导致这些细胞释放包括组胺在内的炎症介质，从而引发过敏症状。Xolair通过与IgE结合，阻止其与FcεRI的结合，从而减少过敏反应的发生。Xolair能够降低游离IgE的水平，减少FcεRI受体的数量，从而减少过敏原触发的炎症级联反应。 根据罗氏第二季度财报披露，Xolair在第二季度的销售额为11.1亿瑞士法郎，同比增加10%。Xolair在美国和欧盟的专利已经过期，但目前市场上尚未有其生物类似药竞争产品上市。尽管面临专利到期的挑战，Xolair依然保持了稳定的销售额增长，这得益于其在多个适应症中的疗效和安全性，以及在新适应症上的不断拓展. 8 Orencia (Abatacept） Orencia（通用名：Abatacept，虽然单季度销售额没有超过10亿美元，但是也接近10亿美元，其在第二季度的销售额为9.48亿美元，Orencia是一种用于治疗类风湿性关节炎（RA）和其他自身免疫性疾病的生物制剂。它是首个通过靶向T细胞治疗RA的生物制剂，通过结合抗原呈递细胞（APCs）表面的CD80和CD86，阻断其与T细胞表面CD28的结合，从而抑制T细胞的激活。Orencia的这种作用机制有助于减少炎症和关节损伤，改善RA患者的症状。 Orencia由百时美施贵宝公司（Bristol-Myers Squibb）开发，最初于2005年在美国获得批准，用于治疗成人中度至重度活动性RA。此后，Orencia也被批准用于治疗幼年特发性关节炎（JIA）和成人银屑病关节炎（PsA）。 在中国，Orencia（商品名：恩瑞舒®）由先声药业与百时美施贵宝合作开发，并已于2020年获得国家药品监督管理局（NMPA）的批准上市 9 Tremfya（guselkumab/特诺雅） Tremfya（guselkumab，商品名：特诺雅）和Orencia类似，单季度销售额虽然也没有过10亿美元，但是达到了9.1亿美元，其是由强生公司开发的一种选择性白细胞介素-23（IL-23）抑制剂，用于治疗中度至重度斑块状银屑病（PsO）和活动性银屑病关节炎（PsA）成人患者。Tremfya的作用机制是阻断IL-23的p19亚基，从而抑制其与IL-23受体的相互作用，减少炎症反应。 在中国，Tremfya于2019年12月获得国家药监局（NMPA）批准上市，用于治疗适合系统性治疗的中重度斑块状银屑病成人患者。此外，Tremfya还被列入了NMPA药品审评中心（CDE）发布的《第一批临床急需境外新药名单》，治疗适应症包括红皮型银屑病、斑块型银屑病、脓疱型银屑病、银屑病关节炎、寻常型银屑病。 10 Rinvoq Rinvoq（Upadacitinib）虽然不是大分子，但是其是免疫治疗药物中唯一一个超过10亿美元的小分子，是由艾伯维（AbbVie）开发的一种Janus激酶（JAK）抑制剂，用于治疗多种炎症性疾病。自从2019年获得美国FDA批准以来，Rinvoq的销售额一直在稳步增长。 Rinvoq的销售额增长得益于其在多个适应症中的成功，包括类风湿性关节炎、银屑病关节炎、强直性脊柱炎、特应性皮炎、溃疡性结肠炎、非放射学中轴型脊柱关节炎和克罗恩病。随着Rinvoq在更多适应症中的应用和市场扩张，预计其销售额将继续增长。此外，Rinvoq被视为艾伯维的“药王”修美乐（Humira）的潜在继任者，随着修美乐专利到期和生物类似药的竞争，Rinvoq和Skyrizi（利生奇珠单抗）被艾伯维寄予厚望，以填补修美乐销售收入的减少。根据2024年上半年的业绩，其第二季度的销售额达到了14.3亿美元，前两个季度销售额为25.2亿美元，Rinvoq前两个季度的销售额同比增长60.4%，表现出强劲的增长势头。 11 总结 感觉没啥好总结的，我们的制药道路任重而道远，别人很多药单季度都突破10亿美元了，我们好像还没有整年销售额超过10亿美元的药吧。 药渡媒体商务合作 媒体公关 | 新闻&会议发稿 张经理：18600036371（微信同号） 点击下方“药渡“，关注更多精彩内容 免责声明 “药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。 微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！👇👇👇

PARIS, France and TARRYTOWN, NY, USA I September 11, 2024 I A Dupixent (dupilumab) confirmatory phase 3 study (LIBERTY-CUPID Study C) met the primary and key secondary endpoints for the investigational treatment of patients with uncontrolled, biologic-naïve CSU receiving background therapy with antihistamines. CSU is a chronic skin condition that causes sudden and debilitating hives and persistent itch, which can impact quality of life. This positive study confirms results from Study A, the first phase 3 study of Dupixent in this setting. Earlier this year, Japan was the first country in the world to approve and launch Dupixent for adult and adolescent CSU patients based on the results from Study A. Dietmar Berger, M.D., Ph.D. Chief Medical Officer, Global Head of Development at Sanofi “The positive pivotal data from this study reinforce the potential of Dupixent to offer a new treatment option for the many people suffering from chronic spontaneous urticaria who do not respond to standard-of-care antihistamines. With clinically meaningful reductions in itch and hives for patients receiving Dupixent, we look forward to sharing these data with the FDA to bring Dupixent to patients with CSU in the US as soon as possible. With Dupixent now treating 1 million patients across seven approved indications, these new results underscore there are still many more patients that Dupixent can potentially benefit.” Study C enrolled 151 children and adults randomized to receive Dupixent (n=74) or placebo (n=77) added to standard-of-care histamine-1 (H1) antihistamines. At 24 weeks, efficacy among patients receiving Dupixent compared to placebo was as follows: Notably, 30% of Dupixent-treated patients reported no urticaria (complete response), compared to 18% of those on placebo (p=0.02). The safety results were generally consistent with the known safety profile of Dupixent in its approved dermatological indications. Overall rates of treatment emergent adverse events (AE) were 53% for Dupixent and 53% for placebo. AEs more commonly observed with Dupixent (≥5%) compared to placebo included injection site reactions (12% vs. 4%), accidental overdose (7% vs. 3%), and COVID-19 infection (8% vs. 5%). Detailed results from this study will be provided to the US Food and Drug Administration in response to the additional data requested for inclusion in the supplemental biologics application for Dupixent in CSU. These data are also planned for presentation at a forthcoming medical meeting. George D. Yancopoulos, M.D., Ph.D. Board Co-Chair, President, and Chief Scientific Officer at Regeneron “Patients with uncontrolled chronic spontaneous urticaria experience debilitating itch and hives that appear without warning and disrupt their lives. With a nearly 50% reduction in itch and urticaria activity scores compared to placebo, these positive phase 3 results reaffirm the potential of Dupixent to bring relief and its well-established safety profile to those living with this chronic inflammatory skin disease.” Outside of Japan, the safety and efficacy of Dupixent for CSU has not been fully evaluated by any regulatory authority. About CSU CSU is a chronic inflammatory skin disease driven in part by type-2 inflammation, which causes sudden and debilitating hives and persistent itch. CSU is typically treated with H1 antihistamines, medicines that target H1 receptors on cells to control symptoms of urticaria. However, the disease remains uncontrolled despite antihistamine treatment in many patients, some of whom are left with limited alternative treatment options. These individuals continue to experience symptoms that can be debilitating and significantly impact their quality of life. About the Dupixent phase 3 CSU program (LIBERTY-CUPID) The LIBERTY-CUPID Phase 3 study program evaluating Dupixent in CSU consists of Study A, Study B , and Study C. Study C was a randomized, double-blind, placebo-controlled clinical study that evaluated the efficacy and safety of Dupixent as an add-on to standard-of-care antihistamines compared to antihistamines alone in 151 patients aged six years and older with CSU who remained symptomatic despite antihistamine use and were not previously treated with omalizumab (i.e., biologic-naïve). The primary endpoint assessed the change from baseline in itch at 24 weeks (measured by the weekly itch severity score [ISS7], 0-21 scale). A key secondary endpoint was the change from baseline in itch and hives at 24 weeks (measured by the weekly urticaria activity score [UAS7], 0-42 scale). Study A supported the approval of Dupixent in Japan for the treatment of CSU in people aged 12 years and older whose disease is not adequately controlled with existing therapy. Results from Study A and Study B, which assessed Dupixent in patients aged 12 years and older who were uncontrolled on standard-of-care H1 antihistamines and refractory to omalizumab, were published in The Journal of Allergy and Clinical Immunology . About Dupixent Dupixent (dupilumab) is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL4) and interleukin-13 (IL13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type-2 inflammation in phase 3 studies, establishing that IL4 and IL13 are key and central drivers of the type-2 inflammation that plays a major role in multiple related and often co-morbid diseases. Dupixent has received regulatory approvals in more than 60 countries in one or more indications including certain patients with atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, prurigo nodularis, CSU, and chronic obstructive pulmonary disease in different age populations. More than 1,000,000 patients are being treated with Dupixent globally. Dupilumab development program Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical studies involving more than 10,000 patients with various chronic diseases driven in part by type-2 inflammation. In addition to the currently approved indications, Sanofi and Regeneron are studying dupilumab in a broad range of diseases driven by type-2 inflammation or other allergic processes in phase 3 studies, including chronic pruritus of unknown origin and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority. About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite ® , which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center ® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases. For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn , Instagram , Facebook or X . About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. SOURCE: Sanofi