A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Tulisokibart in Participants With Moderate to Severe Hidradenitis Suppurativa

This is a phase 2b randomized, double-blind, placebo-controlled study of the safety and efficacy of tulisokibart in participants with moderate to severe hidradenitis suppurativa. The primary hypothesis is that at least 1 dose of tulisokibart is superior to placebo with respect to the proportion of participants achieving a 50% reduction in Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 16 (ie, at end of double-blind treatment).

开始日期2025-06-09

申办/合作机构

Merck Sharp & Dohme LLC

NCT06575595

/ Completed临床1期

A Pharmacokinetic Study of Tulisokibart Administered Subcutaneously Via Autoinjector or Syringe in Healthy Adult Participants

The primary objectives of the study are to characterize the pharmacokinetics (PK) of a single subcutaneous (SC) dose of tulisokibart (MK-7240) administered via autoinjector (AI) (Treatment A) and to characterize the PK of different concentrations of tulisokibart following SC administration of a single dose via vial/syringe (Treatments B and C). There is no formal hypothesis.

开始日期2024-09-24

申办/合作机构

Merck Sharp & Dohme LLC

CTR20241356

/ Recruiting临床3期

一项在中度至重度活动性溃疡性结肠炎受试者中评价MK-7240的有效性和安全性的III期、随机、双盲、安慰剂对照研究

研究1：根据第12周时基于改良Mayo评分达到临床缓解的受试者比例，评价MK-7240与安慰剂相比的有效性。根据第52周时基于改良Mayo评分达到临床缓解的受试者比例，评价MK-7240与安慰剂相比的有效性。评价MK-7240的安全性和耐受性。研究2：根据第12周时基于改良Mayo评分达到临床缓解的受试者比例，评价MK-7240与安慰剂相比的有效性。评价MK-7240的安全性和耐受性。

开始日期2024-06-28

申办/合作机构

默沙东研发（中国）有限公司

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100 项与 Tulisokibart 相关的临床结果

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100 项与 Tulisokibart 相关的转化医学

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100 项与 Tulisokibart 相关的专利（医药）

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项与 Tulisokibart 相关的文献（医药）

2025-06-01·Pharmacology Research & Perspectives

Comparative Efficacy of Different Targeted Therapies in Patients With Moderate‐to‐Severe Ulcerative Colitis: Systematic Review/Network Meta‐Analysis and Mechanistic Overview

Review

作者: Xu, Li ; Sun, Yingzhe ; Hu, Suying ; Hu, Fang ; Pan, Pingting ; Dai, Youran ; Yang, Wenhui ; Li, Qiushuang ; Liu, Shan

ABSTRACT:

Ongoing evaluations of targeted therapies for moderate‐to‐severe ulcerative colitis (UC) continue to unfold, with the emergence of novel drugs. However, head‐to‐head trials comparing these therapies are still lacking. The aim of this study is to investigate the therapeutic effects of targeted therapies in moderate‐to‐severe UC. The Cochrane Library, Web of Science, PubMed, and Embase were searched from the inception to November 12, 2024. Statistical analyses included multivariate random effects models and Bayesian modeling. Stratified and sensitivity analyses were also performed. Publication bias was assessed using funnel plots. Outcomes such as clinical response/remission, endoscopic remission, mucosal healing, quality of life, adverse events (AEs), and serious adverse events (SAEs) were used to quantify the relative therapeutic effects. Thirty‐three studies (33 reported on the induction phase; 13 reported on the maintenance phase) were identified. In the induction phase, Upadacitinib 45 mg demonstrated the highest efficacy in achieving clinical remission (OR 10.03; 95% CI, 4.83–20.80), clinical response (OR 7.96; 95% CI, 3.89–16.28), and mucosal healing rate (OR 8.91; 95% CI, 3.36–23.62). Cobitolimod 250 mg was the first‐ranked treatment (SUCRA, 92.67%) in Endoscopic remission. Vedolizumab 108 mg was the best dosage in reducing Adverse Events (AEs). The optimal dosage for reducing Serious Adverse Events (SAEs) was found to be Tulisokibart 1000/500 mg. During the maintenance phase, Etrasimod 2 mg/kg ranked first in clinical remission (OR 9.58; 95% CI, 2.82–32.59), and Upadacitinib 45 mg was superior in endoscopic remission. Additionally, the most effective medication for raising quality of life was Guselkumab 200 mg (OR 3.04; 95% CI, 1.70–5.40). Consequently, there is a need for further high‐quality research to conclusively determine the best therapeutic option.

2025-05-01·Lancet Gastroenterology & Hepatology

Tulisokibart shows promise for Crohn's disease

Article

作者: Lindsay, James

2025-05-01·Lancet Gastroenterology & Hepatology

Safety and efficacy of the anti-TL1A monoclonal antibody tulisokibart for Crohn's disease: a phase 2a induction trial

Article

作者: Llewellyn, Heather ; Al Kharrat, Houssam ; Longman, Randy S ; Jang, InSock ; Luo, Allison ; Sands, Bruce E ; Marchelletta, Ron ; Targan, Stephan R ; DuVall, Aaron ; McGovern, Dermot P B ; Siegel, Corey A ; Yen, Mark ; Wang, Yong ; Woynarowski, Marek ; Feagan, Brian G ; Bilsborough, Janine ; Anderson, Jaclyn K ; Towfic, Fadi ; Nguyen, Deanna D ; Sabino, João ; Lu, Jiandong ; Kierkus, Jaroslaw ; Laurent, Olivier ; Muñoz-Elias, Ernesto J ; Dubinsky, Marla C

BACKGROUND:

TNF-like cytokine 1A (TL1A) is a key mediator of inflammation and fibrosis. The efficacy and safety of the anti-TL1A monoclonal antibody tulisokibart as induction treatment was assessed in adults with moderately to severely active Crohn's disease with a history of insufficient response, loss of response, or intolerance to conventional or approved biological therapies.

METHODS:

In the phase 2a, multicentre, open-label APOLLO-CD study, participants aged 18 years or older with moderately to severely active Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) of 220-450 and a Simple Endoscopy Score for Crohn's Disease (SES-CD) of at least 6 for ileocolonic or colonic disease or at least 4 for isolated ileal disease, received intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10). This Article reports the results of the primary analysis of the induction period. The primary endpoints were safety and the proportion of participants with endoscopic response at week 12, defined as a decrease in SES-CD of at least 50% from baseline. Safety was analysed in all participants treated with tulisokibart, and endoscopic response was analysed in the per-protocol analysis set, which included all participants treated with tulisokibart with baseline CDAI and SES-CD scores, except those with prespecified important protocol deviations. This trial is registered with ClinicalTrials.gov (NCT05013905) and is closed for recruitment; an open-label extension is ongoing.

FINDINGS:

Of 101 participants screened for eligibility, 55 eligible participants were enrolled and received tulisokibart. The mean age of participants was 39·1 years (SD 15·7), 34 (62%) were male, 21 (38%) were female, and 39 (71%) had received previous biological therapy. At week 12, endoscopic response was observed in 13 (26·0% [95% CI 15·9-39·6]) of 50 participants receiving tulisokibart in the per-protocol analysis set. Adverse events occurred in 43 (78%) of 55 participants, with most adverse events being mild to moderate in severity. The most frequently occurring adverse events (≥5% of participants) were COVID-19 (six [11%] participants), urinary tract infection (five [9%]), Crohn's disease (five [9%]), anaemia (four [7%]), nasopharyngitis (three [5%]), and fatigue (three [5%]). Eight (15%) participants had serious adverse events, none of which were considered related to the study drug by the investigator. There were no deaths.

INTERPRETATION:

This proof-of-concept study showed that tulisokibart is potentially efficacious in moderately to severely active Crohn's disease and is well tolerated. Randomised controlled trials with longer duration are needed to confirm these results; a double-blind, placebo-controlled, phase 3 trial is currently underway.

FUNDING:

Prometheus Biosciences, a subsidiary of Merck & Co, Rahway, NJ, USA.

180

项与 Tulisokibart 相关的新闻（医药）

2025-07-11

·BiG生物创新社

百亿收购拿下全球首创，默沙东发力再造“K药”神话？

作者｜与安7月9日，默沙东宣布与Verona Pharma（下称“Verona”）达成协议，将通过子公司以每股107美元的价格收购Verona的美国存托股票（ADS），较其在纳斯达克前一交易日收盘价溢价23%，较60日成交量加权平均价溢价39%，交易预计今年第四季度完成，总价值约达100亿美元。金额之高，一举成为今年生物医药领域第二大并购案，仅次于此前强生146亿美元收购Intra-Cellular。通过此次收购，默沙东将获得Verona的重磅呼吸病新药Ohtuvayre（ensifentrine，恩司芬群）。这是一款针对磷酸二酯酶3和4（PDE3和PDE4）的first-in-class选择性双重抑制剂，可作为单药或与现有类固醇疗法联用，用于治疗慢性阻塞性肺病（COPD，俗称“烟肺”），也是二十多年来首款新药，自上市以来市场表现十分强劲，目前预计年销售峰值已达数十亿美元，其独特的双重机制和强大的市场潜力为本次重磅交易提供了强力支撑。图1 默沙东宣布收购Verona 01 百亿买局默沙东瞄准“神药第二”默沙东近年的重大交易基本以隔年一次的节奏推进。2021年以115亿美元收购Acceleron及其肺动脉高压（PAH）治疗药物Winrevair，2023年则以108亿美元纳入Prometheus及其晚期肠道疾病候选药物PRA023，而本次收购同样延续了这种步调，以百亿美金的成交金额创下了自2023年以来最大手笔。如此连番豪掷，远不仅是以优势标的对自家管线做强力扩充，更是默沙东面对已然逼近的专利悬崖和增长停摆，为摆脱对王牌产品的过度依赖所做出的关键抉择和战略举措。短期来看，本次交易将为默沙东带来直接有力的营收增长。未来5年，生物医药领域将迎来新一波专利悬崖到期潮，其中不乏多款常年销冠和主力选手，如此形势下，各大药企争相瞄准拥有商业化产品的biotech，以更低风险和即时收益填补专利到期造成的营收鸿沟。现有增长主力中，占据默沙东营收近半壁江山的全球药王Keytruda（pembrolizumab，帕博利珠单抗）即将于2028年迎来专利到期，美国政府预计将在2026年根据IRA对该产品实施谈判，一旦仿制药上市，K药销售额预计暴跌30%-50%，默沙东或将面临近150亿美元的收入缺口。与此同时，第二大畅销产品HPV疫苗Gardasil则直面来自中国国产疫苗的激烈竞争，万泰生物的首款国产疫苗定价499元，相较Gardasil9的1331元直接打了6折。至今年一季度，Gardasil中国市场销售额暴跌约11亿元，其余市场虽整体实现了14％的增长，该药总销售额仍然下降了41％。随着支柱性产品相继面临不确定性，挖掘新的增长主力迫在眉睫。此时这款加速商业化的新药的加入，就显得格外关键。Ohtuvayre自2024年6月底获批上市，市场表现一路走高，至年底便已实现4230万美元销售额，截至今年一季度，更是成倍飙升至7100万美元，环比增长95%，开出处方量已达25000张，新患者启动量环比增长超过25%，且其中60%的处方为续方，表明患者依从性和满意度较高。而自去年8月至今，其商业化甚至还未满一年，市场渗透力可谓惊人。根据SeekingAlpha预测，Ensifentrine的年峰值销售额已达21~36亿美元。如此强劲的市场表现，对默沙东的后续业绩可以说是一针尤为适时的强心剂，有望成为其新的核心增长引擎。图2 PDE3/PDE4双重抑制剂Ohtuvayre而长期考量，Ohtuvayre则将显著丰富默沙东的呼吸系统疾病管线，凭借出色的临床价值和应用前景，与PAH药物Winrevair、呼吸道合胞病毒（RSV）预防药物Enflonsia形成有效协同，推动构建一个多元化、多机制的产品矩阵，推动呼吸管线向第三战略支柱发展，打造更为坚固的竞争壁垒。关于未来交易，默沙东首席执行官Robert Davis此前公开表示，“将会持续寻求10-150亿美元的交易”，这位积极布局管线并购重构的CEO明确表示，“对并购交易持开放态度”，只要目标合适，更大规模的交易仍有可能。 02 全球首创单独给药实现双重疗效根据权威指南《慢性阻塞性肺疾病全球倡议》（GOLD 2025）介绍，COPD是一种异质性、持续性肺部疾病，其特征是由气道和/或肺泡异常导致的慢性呼吸道症状以及持续性、渐进性的气流受限，居全球死因前列，致病机理复杂，主要与吸烟和长期暴露于空气污染有关，俗称“烟肺”。当前治疗手段以3种吸入制剂为主，主要是扩张支气管的长效毒蕈碱拮抗剂（LAMA）和长效β2受体激动剂支气管扩张剂（LABA），以及吸入性糖皮质激素。作为首个用于COPD治疗的新型吸入式机制药物，Ohtuvayre是一款PDE3/PDE4小分子抑制剂，可同时作用于气道平滑肌、炎症细胞、支气管上皮细胞，由此形成其兼具支气管扩张和非甾体抗炎的独特双重机制：•支气管扩张：通过选择性抑制在平滑肌上表达较多的PDE3，舒张气道平滑肌，使呼吸更加顺畅•非甾体抗炎：通过抑制和炎症反应高度相关的PDE4，减轻呼吸道慢性炎症这就直接弥补了当前COPD治疗模式的一大缺陷，即通常绕不开的双联、三联用药，患者需要同时服用不同药物类别的、具有多种作用机制的药物（如支气管扩张剂和吸入性皮质类固醇），才能达到类似效果。通过在单一分子中融合双重疗效，Ohtuvayre由此形成了显著的差异化优势，其通过标准喷射雾化器直接递送至肺部的给药方式，基于相对简化的给药操作，最大化药物在肺部的暴露量、最小化与口服PDE抑制剂相关的全身性副作用，在疗效和安全性之间取得了更好平衡。图3 Ohtuvayre作用机制具体到临床数据上，Ohtuvayre在肺功能方面的出色疗效主要体现于两项关键Ⅲ期临床试验ENHANCE-1和ENHANCE-2。这两项随机、双盲、安慰剂对照多中心试验分别评估了该药作为单一疗法或作为LAMA或LABA的附加药物在40 岁至 80 岁的中重度 COPD 患者中的疗效和安全性。图4 Ohtuvayre两项Ⅲ期试验核心数据结果显示，两项试验中Ohtuvayre均达到主要终点，受试者的肺功能得到显著改善。与安慰剂相比，Ohtuvayre在24周内将COPD急性加重率降低36％-43％，恶化风险降低38%-42%，症状控制情况更加良好，在整个试验过程中表现出良好的耐受性。此外，体外研究表明，Ohtuvayre还能刺激囊性纤维化跨膜电导调节因子（CFTR），或将有助于改善黏液纤毛清除功能并降低黏液粘度。对于伴有慢性支气管炎的患者而言，这一特性可能带来额外的临床获益。目前，Verona Pharma还在探索Ohtuvayre用于治疗非囊性纤维化支气管扩张、囊性纤维化和哮喘等适应症，并开发了Ensifentrine+LAMA（Nebulizer）固定剂量组合疗法，以及ensifentrine吸入粉雾剂（DPI）和定量吸入气雾剂（MDI），进一步加强其临床应用布局的拓展与深化。 03 百亿市场拥抱COPD的广阔前景与挑战由于吸烟率攀高，加之人口老龄化增加患病率，据Research Nester预测，2025年COPD市场预计达到235.4亿美元，2024年全球市场规模超227亿美元，年复合增长率约为4.6％，到2037年将超过407.3亿美元。市场虽然广阔，前路却不好走。过往数十年，其治疗鲜少实现作用机制上的真正突破性，大多数“新药”只是将现有药物类别进行组合，上演一场新瓶装旧酒。但广泛需求却早已明确形成。在使用最大剂量的LAMA/LABA/ICS三联疗法后，仍有相当一部分患者的症状依然持续。以我国情况为例，现有方案治疗下，COPD患者得到有效控制的比例甚至不足5%。重点还是在于研发难度大。对默沙东来说，这也不是其在COPD领域的第一次尝试了，早年放弃开发的Setileuton、MK0873、SCH 351591等都是该适应症药物，最终未能破局。如今引入Ohtuvayre，也意味着该司在COPD领域正式落下一子。如今，各家药企也已先后实现突破，新晋入场的竞争对手包括赛诺菲2024年9月获批的IL-4R单抗度普利尤单抗和GSK今年5月获批的IL-5单抗美泊利珠单抗，蓄力抢占蓝海份额。而国内在研的PDE3/4抑制剂中，则有三款已进入临床阶段，分别是正大天晴的TQC3721、海思科的HSK39004和恒瑞医药的HRS-9821。其中，正大天晴的吸入混悬液剂型TQC3721是国内研发进度最快的国产PDE3/4抑制剂，用于治疗中重度慢性阻塞性肺病，目前位于全球进度第二。其IIa期临床数据显示其有同类最优的潜力，预计2025年启动治疗慢阻肺病（COPD）的Ⅲ期临床。其吸入粉雾剂剂型也已处于治疗COPD的1期临床阶段。海思科的HSK39004同样开发了吸入混悬液和吸入粉雾剂两种剂型，目前已登记Ⅱ期临床研究。恒瑞医药的HRS-9821吸入混悬液则已在去年获批临床试验默示，用于COPD维持治疗。值得一提的是，优锐医药（Nuance Pharma）于2021年获得了Ensifentrine在大中华区临床开发与商业化的独家权利，目前在中国开展的COPDⅢ期临床试验（ENHANCE-CHINA）也已达成主要终点，实现了肺功能显著改善，预计将在今年下半年向NMPA提交新药申请。结语一年不到，已达数十亿美元估值。默沙东大手一挥，再入重磅管线。面对将遇蚕食的市场份额，多方押注的默沙东能否突破重围？背靠巨头的研发和商业化能力，这枚机制独特的商业新星又能否续写K药神话？我们期待后续表现。但无论如何，可以肯定的是，各家药企争相加速推进的临床进展正在打破COPD治疗僵局，为患者带来更为有效的新选择。主要参考文献 1. https://www.merck.com/news/merck-to-acquire-verona-pharma-expanding-its-portfolio-to-include-ohtuvayre-ensifentrine-a-first-in-class-copd-maintenance-treatment-for-adults-and-expected-to-drive-growth-into-the-next-dec/2.Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2025 Report.3.https://www.researchnester.com/cn/reports/chronic-obstructive-pulmonary-disease-market/70514.https://www.fiercepharma.com/pharma/merck-sweetens-its-portfolio-10b-acquisition-verona-and-potential-copd-blockbuster-ohtuvayre5.https://www.fiercepharma.com/pharma/pressuring-mercks-gardasil-china-home-made-9-valent-hpv-vaccine-priced-60-discount6.Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2025 Report.7.Anzueto, A., Barjaktarevic, I. Z., Siler, T. M., Rheault, T., Bengtsson, T., Rickard, K., & Sciurba, F. (2023). Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase Ill Trials (the ENHANCE Trials). Americannjournal of respiratory and critical care medicine, 208(4), 406-416. https://doi.org/10.1164/rccm.202306-0944OC8. 企业官网介绍等公开资料共建Biomedical创新生态圈！如何加入BiG会员？

并购专利到期

2025-07-11

·医药经济报

五年3次100亿美元大并购！默沙东将在何处培育“新药王”？

面对K药专利期临近和HPV疫苗销售放缓的双重压力，默沙东正在急迫寻求新的增长点。7月9日晚，默沙东官宣和专注呼吸系统疾病的生物制药公司Verona Pharma达成最终收购协议。根据协议，默沙东将通过一家子公司以每股107美元的价格收购Verona Pharma的美国存托股份，总交易额约为100亿美元。该交易预计将于2025年第四季度完成。通过此次收购，默沙东将Verona旗下唯一实现商业化的产品——靶向磷酸二酯酶-3 (PDE3)和磷酸二酯酶-4 (PDE4)的双靶点抑制剂恩司芬群（Ensifentrine）纳入麾下，以增强其心肺管线和产品组合。据悉，恩司芬群在2024年6月已经获得FDA批准上市，用于成人慢性阻塞性肺病(COPD，以下简称“慢阻肺”)的维持治疗，成为20多年来首个具有新颖作用机制的慢阻肺吸入性产品。值得注意的是，这已是默沙东在过去5年内完成的第三笔价值百亿美元的收购案。显然，默沙东正在加速业务多元化、扩展产品线，以应对市场竞争加剧和行业格局持续变化。市场充满变数，每一次收购都是对默沙东战略眼光和市场判断的考验，这些潜力管线能否让其继续引领行业潮流，实现更加稳健的增长，尚需时间验证。销售额峰值40亿美元恩司芬群能否实现预期慢阻肺是我国乃至全球主要的公共卫生问题之一，随着人口老龄化和环境因素不断变化，预计未来几十年该疾病负担将继续增长。根据全球疾病负担数据库建模估计，2020—2050年，全球25岁及以上人群慢阻肺的病例数量将增加23%；到2050年，全球有接近6亿慢阻肺病患者。尽管在呼吸药物领域尚未诞生如GLP-1类药物引起广泛关注的突破性品种，然而，庞大的病人基数给这一赛道带来巨大的想象空间。有机构预测，2032年全球慢阻肺病治疗市场销售额将达到约298.8亿美元；在2023-2032年预测期内，复合年增长率为5.14%。2023年以来，慢阻肺早期识别、发病机制、生物标志物和个体化治疗涌现显著进展，Verona获批上市的PDE3/PDE4抑制剂恩司芬群便是缩影。作为全球首创的吸入型双靶点抑制剂，恩司芬群具备扩张气管和抗炎双重效果，还能激活囊状纤维化跨膜转导调节子以降低粘液粘度、改善粘膜纤毛清除；通过普通雾化器直接递送到肺部，不需要复杂的手口协调操作。基于Ⅲ期临床试验ENHANCE-1和ENHANCE-2研究的积极结果，恩司芬群于2024年6月在美国获批，用于成人慢阻肺的维持治疗，2024年8月底在美国上市。迄今，恩司芬群的销售额持续增长，已从2024年第四季度的3660万美元增长到2025年第一季度的7130万美元，接近翻倍。值得一提的是，早在2021年6月，中国药企优锐医药便与Verona签署协议，以2500万美元首付款和可能高达2.19亿美元的总交易额，获得恩司芬群在大中华区域的开发和商业化权益。今年2月，恩司芬群在中国澳门获批上市；5月，优锐医药宣布，恩司芬群治疗慢性阻塞性肺病的Ⅲ期ENHANCE-CHINA研究达到主要终点以及次要终点。基于此，优锐医药计划在今年下半年向NMPA提交该药物的上市申请。有业内观点指出，作为慢阻肺领域全新机制药物，恩司芬群在原有的3种传统作用机制（MOA）基础上带来额外的临床获益，而非击败前者作为替代疗法。有分析师预测，到2035年左右，该药年销售额峰值可能达到近40亿美元。目前，恩司芬群正在探索用于治疗其他肺部疾病，如非囊性纤维化支气管扩张症等。事实上，默沙东对慢阻肺领域并不陌生，据统计，其早年放弃开发的MK0359、Setileuton、MK0873、SCH 351591等都以此为适应症。在业内看来，默沙东广泛的商业足迹和行业领先的临床能力将有助于加速恩司芬群覆盖更多患者，但该药物能否突破目前仅作为慢阻肺患者治疗方案中的补充定位，还有待后续的临床表现和市场反馈。核心产品承压默沙东开启并购模式百亿美元收购Verona的豪赌折射出默沙东对核心产品承压的深切忧虑。自2014年获批上市以来，K药凭借创新的PD-1机制逐步成长为默沙东的“超级现金牛”，2024年销售额将近300亿美元，在蝉联全球药王的同时为默沙东贡献超过46%的营收。但K药在今年一季度的销售额已被诺和诺德的司美格鲁肽反超，并即将在2028年失去核心专利保护，届时默沙东将面临安进、三星生物等企业推出生物类似药的竞争。2028年也是K药在美国上市的第14个年头，该药物将面临Medicare价格谈判的关键节点，或被纳入协商降价框架，量价齐跌显然是默沙东不愿接受的结果。开发皮下剂型、推进联合疗法等，能否帮助默沙东延长K药生命周期，目前来看仍是未知数。不仅如此，默沙东的核心产品HPV疫苗Gardasil/Gardasil 9销售放缓，也是其业绩下滑的主要原因。面对HPV疫苗在中国地需求下降、库存仍居高不下，以及同类国产产品更低价竞争的重重挑战，默沙东已经采取变相降价、拓展男性适应症等举措积极应对，但成效如何，有待今年上半年财报揭晓。在尽力挽回核心产品市场颓势、加速潜力产品成长的同时，默沙东也在用资本换时间、换技术、换市场，开启并购狂潮。这次收购Verona以前，默沙东曾两次斥资百亿美元，先后拿下Acceleron Pharma和Prometheus Biosciences。早在2021年9月，默沙东就宣布将通过子公司按每股180美元的价格，以现金支付方式收购Acceleron，总价值约合115亿美元。Acceleron专注于转化生长因子-β超家族蛋白的开发，其主要候选药物Sotatercept已在2024年3月获得美国FDA批准，用于治疗肺动脉高压（PAH）。默沙东借此切入罕见病赛道，挑战强生等跨国药企在PAH治疗领域的主导地位。但Sotatercept在2024年仅有4.19亿美元销售额，想要成为默沙东寄望的数十亿美元重磅产品，还有较远的路要走。无独有偶，2023年4月，默沙东宣布，将通过子公司以每股200美元的价格收购Prometheus，对应收购总价约为108亿美元。Prometheus是一家处于临床阶段的生物技术公司，主要候选药物PRA023是一种针对肿瘤坏死因子类配体1A（TL1A）的人源化单克隆抗体，与肠道炎症和纤维化有关。根据公开资料，在全球范围内，PRA023正在探索两项Ⅲ期临床研究，针对适应症分别为中重度溃疡性结肠炎和克罗恩病。在中国，该产品已经启动Ⅲ期临床研究，何时上市犹未可知。五年内连续达成三笔百亿美元级别收购，这一激进策略反映了全球头部药企在创新药研发压力下的战略共性，凸显了默沙东面对挑战的野心。未来五年，默沙东的并购成败将成为衡量制药巨头转型范式的关键标尺，其每一步决策都将备受瞩目。能否通过并购实现资源整合，加速新药研发进程，提高市场竞争力，将是默沙东能否在全球制药行业继续保持领先地位的关键。编辑：范晓艳、李咏诗版式编辑：余远泽审校：马飞、张松基药喜提大利好，一省医联体用药目录遴选优先使用多款原研药主动注销意欲为何？辉瑞、GSK等巨头转身投向新赛道5家药店被通报，8款药品被点名！国家医保局严打欺诈骗保www.yyjjb.com.cn洞悉行业趋势长按关注医药经济报《中国处方药》学术公众号聚焦药学学术和循证研究长按关注中国处方药《医药经济报》终端公众号记录药品终端产经大事件长按关注21世纪药店

并购疫苗临床3期专利到期

2025-07-09

·FiercePharma

Merck boosts respiratory portfolio with $10B acquisition of Verona and potential COPD blockbuster Ohtuvayre

For the third time in the last five years, Merck has pulled off an acquisition in the $10 to $12 billion range, buying out Verona Pharma and its potential COPD blockbuster Ohtuvayre. Merck has pulled off another acquisition which fits in its “sweet spot,” as described by CEO Rob Davis, paying $10 billion for Verona Pharma and its potential blockbuster Ohtuvayre, a first-in-class treatment for chronic obstructive pulmonary disorder (COPD).It is the second-largest deal in biopharma this year, ranking behind Johnson & Johnson’s $14.6 billion buyout of Intra-Cellular, and fits Merck’s pattern of striking every other year with a major transaction.In 2021, Merck spent $11.5 billion for Acceleron and its pulmonary arterial hypertension (PAH) treatment, now known commercially as Winrevair. Then in 2023, the New Jersey company ponied up $10.8 billion for Prometheus and its late-stage bowel disease candidate PRA023.The acquisitions are designed to compensate for the expected loss of patent protection later this decade for cancer superstar Keytruda, which generated $29.5 billion in sales in 2024, accounting for 46% of the company’s revenue.“The sweet spot we see is that $1 to $15-billion range,” Davis said in conference call on Wednesday. “As we’ve also consistently indicated, we’re willing to go beyond that for the right opportunity.”Additionally, Davis said that the company plans to launch roughly 20 “new growth drivers in the coming years, almost all of which have blockbuster potential.” He added that Merck will continue to scout out oncology, immunology and cardiometabolic assets through business development.As for the buyout of Verona, Merck has agreed to pay $107 per share, which is a 23% markup on their price at market close Tuesday and a 39% premium on their 60-day volume-weighted average price. The companies expect the deal to close in the fourth quarter of this year.The FDA approved Ohtuvayre 13 months ago as the first novel inhaled treatment for COPD in more than two decades. The drug can be used as a monotherapy or as an add-on medicine with current steroid therapies. As a selective dual inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes, Ohtuvayre combines two properties in one medicine, setting it apart from COPD competitors for its ability to both open the airways of patients and reduce their inflammation.Ohtuvayre is off to a solid launch, generating sales of $71 million in the first quarter of this year, good for 95% growth sequentially. During the three months, 25,000 prescriptions were filled, up from 16,000 in 2024.“Since launching Ohtuvayre in August 2024, we have seen rapid and accelerating uptake in the U.S.,” Verona CEO David Zaccardelli said in a release Wednesday. “We believe Merck’s commercial footprint and industry-leading clinical capabilities will help accelerate the potential of Ohtuvayre to reach more patients living with COPD.” The treatment has not been approved in Europe. Some of that advantageous footprint comes through Merck’s commercialization of Winrevair. Although it is a product for a rare lung disease, many of the physicians who prescribe Winrevair will have patients with COPD.The prescriber base for the disease is 14,500 in the U.S., according to Merck’s human health president Jannie Oosthuizen. Verona reported in April that 5,300 doctors had prescribed Ohtuvayre in the first quarter.“I think our scale brings a good ability to expand fairly rapidly into that broader prescriber base, educate and get Ohtuvayre to be added to existing background therapies, especially in those patients with persistent symptoms,” Oosthuizen said, adding that the company expects the market to grow from $17 billion this year to $27 billion by 2032. Meanwhile, other companies are rushing to the COPD space. After a delay, the FDA in May approved GSK's antibody drug Nucala as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype. Amgen and AstraZeneca have hopes for their asthma drug Tezspire as a potential COPD treatment.Last year, Regeneron and Sanofi gained approval for Dupixent to treat COPD exacerbations. The companies also have a second COPD candidate in IL-33 inhibitor itepekimab, which is being tested in two phase 3 trials.

上市批准并购临床3期

100 项与 Tulisokibart 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
克罗恩病	临床3期	美国	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	中国	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	日本	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	澳大利亚	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	奥地利	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	比利时	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	加拿大	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	智利	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	哥伦比亚	Merck Sharp & Dohme LLC	2024-06-05
克罗恩病	临床3期	克罗地亚	Merck Sharp & Dohme LLC	2024-06-05

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


UEGW2024	N/A	溃疡性结肠炎	-	Tulisokibart 100 mg	鹽夢襯廠獵鬱築顧醖網(夢膚醖衊淵壓憲蓋壓夢) = Through week 50, AEs occurred in 63% and 77% of patients receiving tulisokibart 250 mg and 100 mg, respectively; most were mild to moderate in severity. Serious AEs occurred in 1 patient (3%) and two patients (7%) in the tulisokibart 250 mg and 100 mg groups, respectively. 顧觸獵糧觸構積壓繭齋 (膚築鏇淵顧鹹選遞襯廠 )	-	2024-10-13
				Tulisokibart 250 mg
NCT04996797 (ARTEMIS-UC, Pubmed \| N Engl J Med) 人工标引	临床2期	溃疡性结肠炎	135	Tulisokibart	鏇餘選範艱築鬱襯製鹽(獵製糧鹹鹹簾鏇窪鏇醖) = 餘網觸網鏇齋構鑰鏇繭窪廠網構構鏇醖糧鬱齋 (鹹鹽選選鏇艱築範網襯 )	积极	2024-09-26
				Placebo	鏇餘選範艱築鬱襯製鹽(獵製糧鹹鹹簾鏇窪鏇醖) = 鏇積觸壓膚艱鹹構齋糧窪廠網構構鏇醖糧鬱齋 (鹹鹽選選鏇艱築範網襯 )
NCT04996797 (ARTEMIS-UC, CTgov)	临床2期	溃疡性结肠炎	178	Tulisokibart (Cohort 1 Tulisokibart)	襯齋鬱蓋製鹽膚鏇餘鬱 = 鬱願廠糧顧獵醖膚鹹餘衊衊艱鏇繭齋齋觸顧獵 (願觸遞衊窪範構齋簾鏇, 糧蓋觸糧鏇廠壓壓糧夢 ~ 築膚顧鏇蓋鏇襯觸憲簾) 更多	-	2024-06-27
				Placebo (Cohort 1 Placebo)	襯齋鬱蓋製鹽膚鏇餘鬱 = 膚遞鑰顧鬱憲鑰願積觸衊衊艱鏇繭齋齋觸顧獵 (願觸遞衊窪範構齋簾鏇, 積遞構積廠顧鑰壓淵範 ~ 糧窪膚願糧網廠獵鑰願) 更多
NCT05013905 (APOLLO-CD, CTgov)	临床2期	克罗恩病	55	Companion diagnostic (CDx)+PRA023 IV	夢範襯淵衊築範願醖製 = 憲選遞蓋餘範淵醖餘鹹糧廠簾鬱選衊醖夢鹽觸 (觸廠構蓋餘蓋壓艱築蓋, 顧鏇範鹽壓齋選淵獵鹹 ~ 積觸獵醖壓繭願夢範鏇) 更多	-	2023-11-01
NCT04996797 (ARTEMIS-UC, UEGW2023)	临床2期	活动性中度溃疡性结肠炎 eosinophils \| neutrophils	135	PRA023	顧糧範觸鬱遞衊膚願製(艱觸遞鏇鹽觸衊獵糧網) = 構鹽鑰醖觸獵鹹夢簾廠築繭齋簾襯憲遞齋構夢 (鏇觸餘繭簾遞齋餘築鑰 ) 更多	积极	2023-10-15
				Placebo	顧糧範觸鬱遞衊膚願製(艱觸遞鏇鹽觸衊獵糧網) = 觸繭鹹鏇醖鏇鏇壓艱壓築繭齋簾襯憲遞齋構夢 (鏇觸餘繭簾遞齋餘築鑰 ) 更多
UEGW2023	N/A	活动性中度溃疡性结肠炎	-	PRA023	網鏇範艱廠廠壓鏇廠範(膚醖鹽鬱選築鏇繭夢窪) = 遞選齋選蓋構膚鹹壓選選憲窪選網繭顧構願選 (築繭鑰顧淵醖艱襯獵憲, 34.85) 更多	-	2023-10-15
				Placebo	網鏇範艱廠廠壓鏇廠範(膚醖鹽鬱選築鏇繭夢窪) = 餘顧繭襯廠鑰糧鏇網獵選憲窪選網繭顧構願選 (築繭鑰顧淵醖艱襯獵憲, 37.59) 更多
ARTEMIS-UC \| COHORT 1 (UEGW2023)	临床2期	活动性中度溃疡性结肠炎 TL1A	135	PRA023	網淵願鹹憲簾艱窪窪齋(觸簾網範廠繭憲壓膚鹹) = 選鹹鹹範壓鑰鹽製鏇鹽蓋廠獵廠簾製積觸獵觸 (廠衊衊鬱衊鹽遞夢鬱鑰 ) 更多	积极	2023-10-15
				Placebo	網淵願鹹憲簾艱窪窪齋(觸簾網範廠繭憲壓膚鹹) = 鹹艱糧憲繭繭淵鑰選鑰蓋廠獵廠簾製積觸獵觸 (廠衊衊鬱衊鹽遞夢鬱鑰 ) 更多