炎症性肠病：巨头争霸，高潮迭起

2024-06-28

并购临床3期上市批准申请上市

近几年，非肿瘤领域的临床需求逐渐进入众多制药企业的视野，尤其是肥胖、代谢功能障碍相关脂肪性肝炎（MASH）、炎症性肠病（IBD）等疾病领域。其中，IBD作为西方国家的高发疾病，是制药巨头的重点关注对象。 1998年，英夫利西单抗获FDA批准用于治疗克罗恩病（CD），开启了IBD的靶向治疗之路。如今26年光景过去，IBD领域的创新靶向疗法已多达13款，其中最畅销药物维得利珠单抗（主要适应症为IBD）的销售额已超50亿美元。获批IBD适应症的靶向药物（亿美元）注：维得利珠单抗的销售额为自然年收入。疾病负担的加重仍在推动IBD市场规模的扩大。目前全球约有600-800万IBD患者[1,2]，其中欧美国家IBD患者已超过500万。而中国的IBD发病率也在快速增长，2019年患者规模已达到91万[3]。据Transparency Market Research预测，IBD市场规模到2030年将达到490亿美元。如此庞大的市场需求也吸引了众多玩家入局。自2023年至今，IBD领域已达成23项交易，交易额总计超200亿美元。 2023年至今IBD领域重大交易（亿美元）注：仅统计总交易额超1亿美元的合作/收购交易 BD交易如火如荼进行的同时，IBD领域的产品开发争霸赛也高潮迭起。目前，阿达木单抗、乌司奴单抗、维得利珠单抗、乌帕替尼和利生奇珠单抗是在IBD领域激战正酣的五大明星产品。 IBD领域五大明星产品疗效一览注：1）阿达木单抗的溃疡性结肠炎疗效数据选自GAIN研究，因其同时纳入了欧美人群；2）*为诱导治疗数据；#为维持治疗数据；3）以上研究的对照组均为安慰剂组。阿达木单抗凭借着至少7年的先发优势，再加上在类风湿性关节炎、银屑病关节炎和强直性脊柱炎三项自免适应症上的市场渗透经验，抢占IBD市场份额算是轻车熟路。但是在维得利珠单抗上市之后，阿达木单抗在IBD领域的地位开始下降。因为anti-α4β7提供了更强的靶向治疗效果[18]，维得利珠单抗在针对UC的头对头研究中成功击败了阿达木单抗[19]。靶向IL-12/IL-23的乌司奴单稍晚一些加入战局，试图冲击IBD药物的市场格局。不过，相比于前两款产品，乌司奴单抗针对IBD的治疗效果并未有明显提升，这恐怕也是其销售额在获批CD适应症后未大幅上升的原因之一。遗憾的是，其挑战阿达木单抗的III期SEAVUE研究也以失败告终[20]。作为自免疾病赛道的领军企业，强生在IL-23靶点上推陈出新和巩固优势。新一代产品古塞奇尤单抗在IBD领域也交出一份满意的答卷。今年4月，古塞奇尤单抗对比乌司奴单抗治疗CD的两项头对头研究大获成功，而其诱导治疗和维持治疗UC的III期QUASAR研究也顺利达到主要终点。IBD的战局迎来一个实力选手。艾伯维的当家产品阿达木单抗失去市场独占期，但接棒产品乌帕替尼已经成长起来。在IBD的适应症上，无论是诱导治疗还是维持治疗，乌帕替尼对CD和UC均有着超群的治疗效果。口服的独特优势也让其在市场竞争中如虎添翼。上市第5年，乌帕替尼的年销售额已接近40亿美元。利生奇珠单抗是艾伯维在IBD领域的另一个筹码，该产品已在头对头研究中打败乌司奴单抗。从临床数据来看，乌帕替尼、利生奇珠单抗和古塞奇尤单抗在IBD上的疗效范围接近，未来几年IBD领域的战况也将是这三款产品主导。 3款产品疗效一览注：1）*为诱导治疗数据；#为维持治疗数据；2）除红色标注数据的对照组为乌司奴单抗外，其余研究的对照组均为安慰剂。 IBD作为市场规模可观的自免疾病之一，难免会让药企趋之若鹜，包括靶向IL-23的药物竞争也着实激烈。除了艾伯维和强生在这一赛道双龙际会，礼来的IL-23单抗mirikizumab正迎头赶上，还有多款国产IL-23靶向药物对国内IBD市场虎视眈眈。竞争激烈如斯，同赛道玩家阿斯利康已及时止损。国产IL-23靶向药物在研情况临床需求尚未得到充分满足的IBD领域已成为药企扩张自免业务版图的不二选择，其战况已有日益焦灼之势。自英夫利西单抗上市以来，靶向TNF-α、IL-12、IL-23等炎症因子的疗法已统治IBD领域二十多年，不过这种局面正在发生改变。去年7月，默沙东高价收购Prometheus Biosciences让TNF样配体1A（TL1A）靶点开始进入IBD玩家的视野。目前该赛道已达成4项授权/收购交易，总交易额超200亿美元，热度瞩目。未来，IBD领域的市场之战也将有TL1A抗体的一席之地。国内药企诸如康方生物、信达生物、恒瑞医药等也在奋力加入战局。未来这个赛道将碰撞出怎样的火花，且拭目以待吧。 - 上下滑动查看参考资料 - [1] The epidemiology of inflammatory bowel disease: East meets West. [2] The four epidemiological stages in the global evolution of inflammatory bowel disease. [3] Landscape and predictions of inflammatory bowel disease in China: China will enter the Compounding Prevalence stage around 2030. [4] Adalimumab Induction Therapy for Crohn Disease Previously Treated with Infliximab. [5] Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. [6] Adalimumab Induces and Maintains Clinical Remission in Patients With Moderate-to-Severe Ulcerative Colitis. [7] Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. [8] Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. [9] Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. [10] Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis. [11] Vedolizumab as induction and maintenance therapy for Crohn's disease. [12] Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. [13] Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. [14] Risankizumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomized Phase 3 INSPIRE Study. [15] Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. [16] 艾伯维新闻稿. https://www.prnewswire.com/news-releases/risankizumab-skyrizi-met-primary-and-key-secondary-endpoints-in-52-week-phase-3-maintenance-study-in-ulcerative-colitis-patients-301851542.html. [17] Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. [18] https://www.entyviohcp.com/mechanism-of-action. [19] Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. [20] Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. [21] The Efficacy and Safety of Guselkumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Induction Study. [22] 强生新闻稿. https://www.businesswire.com/news/home/20201012005149/en/TREMFYA%C2%AE%E2%96%BC-guselkumab-Induces-Clinical-and-Endoscopic-Improvements-in-Patients-with-Moderately-to-Severely-Active-Crohn%E2%80%99s-Disease-based-on-Interim-Results-from-Phase-2-Study. [23] 强生新闻稿. https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-quasar-maintenance-study-in-uc-met-its-primary-endpoint-and-all-major-secondary-endpoints-including-highly-statistically-significant-rates-of-endoscopic-remission. [24] 强生新闻稿.https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-demonstrates-superiority-versus-stelara-ustekinumab-in-phase-3-crohns-disease-program. 推荐阅读制药巨头新宠：炎症性肠病皇冠靶点迎来“新明珠”，多发性骨髓瘤一线治疗格局再现风云 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。 —医药决策者们，请进 —