A Phase 3 Extension Study to Evaluate the Long-term Safety and Efficacy of Tulisokibart in Participants With Crohn’s Disease or Ulcerative Colitis - MK-7240-011

开始日期2025-03-04

申办/合作机构

Merck Sharp & Dohme LLC

NCT06651281

/ Recruiting临床3期

A Phase 3 Extension Study to Evaluate the Long-term Safety and Efficacy of Tulisokibart in Participants With Crohn's Disease or Ulcerative Colitis

Researchers want to learn more about tulisokibart (also known as MK-7240) in an extension study. Tulisokibart is a medicine designed to treat active, moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). An extension study is a type of study where people who received tulisokibart in certain other studies for CD or UC (called a parent study) may be able to join this study. The goals of this study are to learn about the safety of tulisokibart over time in people with CD or UC, and if people tolerate it.

开始日期2024-11-25

申办/合作机构

Merck Sharp & Dohme LLC

CTIS2023-508636-61-00

/ Recruiting临床3期

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Program to Evaluate the Efficacy and Safety of Tulisokibart in Participants with Moderately to Severely Active Crohn’s Disease - MK-7240-008

开始日期2024-11-06

申办/合作机构

Merck Sharp & Dohme Corp.

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）

2025-03-01·Revue medicale de Liege

[Intestinal fibrosis in Crohn's disease : towards new therapeutic options?]

Review

作者: Vieujean, Sophie ; Stepniak, Marty ; Meuwis, Marie-Alice ; Louis, Édouard ; Bequet, Émeline

Crohn's disease is a chronic inflammatory bowel disease that can lead to fibrostenotic complications. These strictures result from an imbalance between inflammation and excessive healing, leading to an abnormal accumulation of extracellular matrix and a progressive thickening of the intestinal wall. To date, no specific treatment is available to prevent or reverse intestinal fibrosis. The management of strictures primarily focuses on controlling inflammation and addressing obstructive complications through endoscopic balloon dilation, stricturoplasty, or intestinal resection. Current medical therapies, such as anti-TNF agents, can help reduce inflammation but have no direct impact on fibrosis. New therapeutic strategies are emerging, including TL1A inhibitors (duvakitug, tulisokibart), an ALK5 inhibitor (AGMB-129), and targeted AGR2 therapies (TH-009). Additionally, mesenchymal stem cells are being investigated in our hospital center in combination with endoscopic balloon dilation, aiming to assess their therapeutic potential. The development of effective anti-fibrotic therapies remains a critical medical need to improve the management of intestinal strictures and reduce the need for invasive procedures in Crohn's disease.

2024-09-26·NEW ENGLAND JOURNAL OF MEDICINE

Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis

Article

作者: Luo, Allison ; Ritter, Timothy E ; Ma, Christopher ; Leszczyszyn, Jaroslaw ; Feagan, Brian G ; Sands, Bruce E ; Lu, Jiandong ; Yen, Mark ; Targan, Stephan ; Nguyen, Deanna D ; Laurent, Olivier ; McGovern, Dermot P B ; Danese, Silvio ; Peyrin-Biroulet, Laurent ; Kempiński, Radosław ; Rubin, David T

BACKGROUND:

Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.

METHODS:

We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses.

RESULTS:

In cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P = 0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity.

CONCLUSIONS:

In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.).

2024-01-01·Advances in pharmacology (San Diego, Calif.)

TL1A: A model for a precision medicine approach in the treatment of Crohn’s disease and ulcerative colitis

Review

作者: Bilsborough, Janine M ; Targan, Stephan R. ; Targan, Stephan R ; Bilsborough, Janine M.

Inflammatory bowel disease (IBD) is a collective term for chronic inflammatory diseases of the intestinal tract. The term IBD encompasses two main forms, Crohn's disease (CD) and Ulcerative colitis (UC). CD is characterized by inflammation throughout the length of the gut, especially the ileum and colon, and is often complicated with fistulae and/or intestinal strictures. Ulcerative colitis (UC) is inflammatory disease restricted to the colon and rectum. In practice however, IBD is a heterogenous disease with CD and UC representing the extremes of a continuum of diseases with varied clinical presentation, including disease location, severity, and manifestation of extraintestinal diseases. This disease heterogeneity poses a challenge to successful and efficacious therapeutic treatment as the etiology driving disease in individual patients is unknown and likely to be multifactorial, including genetic predisposition, environmental factors such as the microbiota, as well as social behaviors such as smoking and diet. Precision medicine provides a strategy to account for disease heterogeneity and diverse etiology to select for patients most likely to respond to a given therapeutic. In this chapter we present an example of the development of a novel antibody therapeutic, Tulisokibart, as a model for a Precision Medicine approach to the successful treatment of patients with IBD.

166

项与 Tulisokibart 相关的新闻（医药）

2025-04-16

·生物世界

Nature“风向标”综述：这些自身免疫疾病靶点，或将诞生下一个药王！改写百亿美元神话

自身免疫疾病是免疫系统“自相残杀”的结果，核心机制是免疫系统自我识别功能紊乱，导致炎症反应和组织损伤。目前已知的自身免疫疾病超过 100 种，常见的包括系统性红斑狼疮、类风湿性关节炎、银屑病、多发性硬化症、1 型糖尿病等。过去 30 年，靶向调节免疫反应的信号通路成为治疗自免疾病“炙手可热”的方法。自免疾病领域不仅市场增速快，而且时常见证“百亿美元分子”重磅药物的诞生。据 BioSpace 统计，2024 年全球药品销售额 TOP10 中，4 款为自免类药物，合计销售额达 440 亿美元，包括赛诺菲/再生元的 Dupixent（度普利尤单抗），艾伯维的 Skyrizi（瑞莎珠单抗）、Humira（阿达木单抗），强生的 Stelara（乌司奴单抗）。可谓是前有“药王”阿达木，后有来者度普利尤。近日，引领药物发现研究“风向标”的 Nature Reviews Drug Discovery 期刊发表了题为：Trends in the drug target landscape for autoimmune diseases 的文章，分析了 2020-2024 年间自身免疫疾病药物靶点的发展趋势，下一个“药王”或将从这些靶点中诞生。卷出天际：自免在研药物暴增 47%文章对近 5 年在研的 92 个自免相关靶点或靶点组合进行统计，发现正在开发的自免药物数量从 2020 年的 131 种增加到 2024 年的 193 种，“暴增”47%。下图展示了 2020-2024 年间在研和上市的自免药物数量的动态变化。热门自免靶点统计图近 5 年至少有 4 款自免“first-in-class”药物上市，分别靶向 IL-13、IL-31、IL-36 及TYK2，适应症主要为皮肤类自免疾病，例如特应性皮炎、结节性痒疹、银屑病。TNF 超家族的靶点研发进展取得显著进展。2020 年，该家族靶点除 TNFα 外，仅有 CD40-CD40L 进入临床 Ⅲ 期。而到了 2024 年，靶向 OX40、TL1A、RANK、BAFF 等靶点的药物也都进入临床 Ⅲ 期。例如，TL1A 靶点有 3 款用于治疗炎症性肠病的药物进入 Ⅲ 期，分别为 Duvakitug（来自赛诺菲）、RG6631（来自罗氏）和 Tulisokibart（来自默沙东）。靶向白介素的创新研究有多种因素推动，比如选择性更高（IL-17A/F抑制剂）、活性持续时间更长（GSK的长效IL-15抑制剂）以及新技术的应用（礼来靶向IL-17的口服药）。IL-4、IL-18、IL-33 具有成为“first-in-class”靶点的潜力。IL-1 受体相关激酶 IRAK4 备受关注，因为它有望用一种药抑制整个 IL-1 家族（IL-1、IL-18、IL-33、IL-36）。这些白介素因子靶点与银屑病和哮喘有关。TSLP 靶点也备受关注，因为它作用于 2 型炎症激活因子 IL-4、IL-5 和 IL-13。TYK2 抑制剂正受到越来越多的关注。TYK2 作用在免疫反应的下游，与 IL-12 和 IL-23 信号通路相关，参与银屑病、克罗恩病的发病过程。与 JAK 抑制剂相比，TYK2 抑制剂不会影响造血功能。目前有多种联合治疗策略用于进一步扩宽治疗方案，例如同时靶向 IL-17 和 TNF，或使用双激酶抑制剂（JAK1、JAK2、JAK3与TYK2、SYK、TEC）。2023 年辉瑞研发的 LITFULO（Ritlecitinib）获得 FDA 批准，用于治疗 12 岁以上的重度斑秃患者。LITFULO 是一种口服的共价 JAK3/TEC 双激酶抑制剂，抑制 IL-15 和 CD8 细胞因子的信号转导，从而抑制免疫系统杀伤毛囊细胞，达到治疗斑秃的目的。即将到来的创新潮自免靶点研发管线保持高度活跃，未来几年将会产生多款 first-in-class 疗法。例如 TL1A、OX40、TSLP、IL-33 和 TYK2 等靶点潜力大，IL-17、IL-23 和 JAK 抑制剂在 best-in-class 创新方面也在不断增加，靶向 IL-4、IL-13 和 IL-15 的研发也将有更多的 2 型炎症性疾病适应症。预示着自身免疫性疾病治疗的新纪元。义翘神州提供全面的自身免疫疾病解决方案，试剂涵盖近 50 种自免疾病。产品包括靶点蛋白、细胞因子和激酶，以及用于生物标志物研究的试剂。义翘神州为生物标志物分析和药物研发提供高质量的科研工具，在推动自身免疫性疾病的早期检测和靶向治疗开发中发挥关键作用。参考文献：Alexandre Fauconnier, et al. Trends in the drug target landscape for autoimmune diseases. Nature Reviews Drug Discovery, 2025. https://doi.org/10.1038/d41573-025-00061-7

临床3期免疫疗法

2025-04-15

·PRNewswire

Takeda's ENTYVIO Continues Growth Trajectory in Ulcerative Colitis and Crohn's Disease | DelveInsight

With the introduction of a subcutaneous formulation, ENTYVIO has expanded patient convenience and global accessibility. Continued growth is supported by rising IBD prevalence and ongoing geographic expansion. LAS VEGAS, April 15, 2025 /PRNewswire/ -- DelveInsight's " ENTYVIO Market Size, Forecast, and Market Insight Report" highlights the details around ENTYVIO, a gut-selective biologic developed by Takeda Pharmaceutical. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of ENTYVIO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Takeda Pharmaceutical's ENTYVIO (vedolizumab) Overview Vedolizumab is a biologic medication approved for both intravenous (IV) and subcutaneous (SC) use, with regulatory approvals varying by region. The SC formulation is authorized for use in the United States, European Union, and over 50 other countries, while the IV formulation has received approval in more than 70 countries, including the US and the EU. Collectively, vedolizumab IV and SC have accumulated over one million patient-years of global exposure. Vedolizumab is a humanized monoclonal antibody that selectively targets the alpha4beta7 integrin, blocking its interaction with mucosal addressin cell adhesion molecule 1 (MAdCAM-1) — a protein primarily found on blood vessels and lymph nodes in the gastrointestinal tract. This integrin is present on certain white blood cells involved in the inflammatory processes of ulcerative colitis and Crohn's disease. By disrupting the binding between alpha4beta7 integrin and MAdCAM-1, vedolizumab may reduce the migration of these immune cells into the gut, thereby decreasing inflammation. ENTYVIO Dosage For adults with ulcerative colitis, the advised dosage of ENTYVIO is 300 mg given through intravenous infusion at weeks 0, 2, and 6, followed by maintenance infusions every 8 weeks. Treatment should be discontinued if no clinical improvement is observed by week 14. Learn more about ENTYVIO projected market size for Crohn's disease and ulcerative colitis @ ENTYVIO Market Potential Crohn's disease is a progressive type of inflammatory bowel disease (IBD) that results in chronic inflammation throughout the gastrointestinal tract, most commonly affecting the terminal ileum and colon. This inflammation can lead to complications such as strictures, fistulas, and ulcers. In 2024, there were 1.1 million diagnosed prevalent cases of Crohn's disease in the United States. Current treatment approaches primarily include biologics such as adalimumab (HUMIRA and its biosimilars), ustekinumab (STELARA), infliximab (REMICADE and biosimilars), along with systemic corticosteroids, immunosuppressants, 5-aminosalicylic acid (5-ASA), and other therapies. Among these, adalimumab held the largest market share in the 7MM in 2024, generating around USD 4 billion in revenue for Crohn's disease treatment. In 2024, the market size of Crohn's disease was highest in the US among the 7MM, accounting for approximately USD 8 billion, which is further expected to increase at a CAGR of 4.5%. The Crohn's disease market is projected to expand due to the introduction of novel therapies with improved efficacy and more convenient routes of administration, broader use of biologics in pediatric populations, growing commercial opportunities in biologic-treated patients, advancements in biomarker development for early diagnosis, and the overall rising prevalence of the disease. Discover more about the Crohn's disease market in detail @ Crohn's Disease Market Report Ulcerative colitis is one of the primary types of chronic inflammatory bowel disease (IBD) affecting the gastrointestinal tract. It is an idiopathic and long-standing inflammation of the colonic mucosa, typically presenting with symptoms like diarrhea, abdominal discomfort, and rectal bleeding. In 2023, there were an estimated 3.1 million diagnosed prevalent cases of ulcerative colitis across the 7MM, with numbers expected to rise over the forecast period. According to current US treatment guidelines, mild-to-moderate cases are initially managed with aminosalicylates or by using corticosteroids for induction followed by maintenance therapy with aminosalicylates. For patients with moderate-to-severe disease, maintenance treatment may involve immunosuppressants like azathioprine or 6-mercaptopurine after corticosteroid induction. Alternatively, biologics—particularly anti-TNF agents such as infliximab or adalimumab—can be used alone or alongside immunosuppressants to achieve and sustain remission and mucosal healing. The treatment landscape across the 7MM is categorized into commonly used drug classes, including conventional therapies, anti-TNF agents, anti-adhesion molecule therapies, JAK inhibitors, and others, reflecting some variations in prescribing practices. Looking ahead, the anticipated introduction of novel therapies, increased focus on early detection, enhanced use in secondary care, improved implementation strategies, and growing disease awareness are likely to contribute to more effective management of ulcerative colitis. As a result, the ulcerative colitis market will grow from USD 8.4 billion in 2023 at a significant CAGR by 2034. However, the high costs of new treatments and the financial burden of disease complications may pose challenges to widespread adoption. For a comprehensive view of the ulcerative colitis market, check out the Ulcerative Colitis Market Assessment Emerging Competitors of ENTYVIO Despite the presence of biosimilars, innovation in Crohn's disease and ulcerative colitis treatment remains strong, with several emerging therapies exploring new inflammatory pathways to improve efficacy and long-term outcomes. RHB-104, a combination macrolide antibiotic, is in Phase III trials targeting potential mycobacterial involvement. VELSIPITY, an S1P receptor modulator, works by limiting lymphocyte migration and reducing inflammation. TREMFYA, which inhibits IL-23, is under evaluation for its immune-modulating effects, while ABBV-154, a TNF inhibitor conjugated with a steroid, aims to enhance TNF suppression. Additional pipeline therapies include Merck's TL1A inhibitor Tulisokibart (PRA023/MK-7240) in Phase III and Pfizer's JAK3 inhibitor LITFULO in Phase II. Teva and Sanofi are also developing Duvakitug, a monoclonal antibody targeting TNFSF15. These investigational drugs represent significant progress for patients unresponsive to current treatments. A range of other promising candidates are in development, each targeting unique pathways. Landos Biopharma's Omilancor (BT-11) is in Phase II and acts via LANCL2, while AVB-114 from Avobis Bio/Alimentiv is also in Phase II. Abivax S.A.'s Obefazimod (ABX464) is being studied for its ability to upregulate miR-124. Roche's RVT-3101 (RG6631), an anti-TL1A antibody, is in Phase II trials, and Mesoblast's RYONCIL (Remestemcel-L), a mesenchymal stem cell therapy, is progressing in Phase III, offering regenerative potential. Other noteworthy agents in Phase II include Zasocitinib (TAK-279) from Takeda, a TYK2 inhibitor; AZD7798 from AstraZeneca, targeting CCR9; Sanofi's Balinatunfib (SAR441566), which blocks TNFR1 signaling; AGMB-129 from Agomab Therapeutics, targeting ALK5/TGFβR1; MBF-118 by Medibiofarma, a PPARγ partial agonist; and MORF-057 by Eli Lilly and Morphic Therapeutic, an α4β7 integrin inhibitor. Together, these developments illustrate a robust and diversified IBD pipeline. To know more about the number of competing drugs in development, visit @ ENTYVIO Market Positioning Compared to Other Drugs Key Milestones of ENTYVIO In April 2024, Takeda announced that the FDA has approved the subcutaneous (SC) formulation of ENTYVIO (vedolizumab) for maintenance treatment in adults with moderately to severely active Crohn's disease who have previously received induction therapy with the intravenous (IV) form of ENTYVIO. In September 2023, Takeda announced that the FDA has approved the SC formulation of ENTYVIO to be used as maintenance therapy in adults with moderately to severely active ulcerative colitis following induction treatment with the IV version of ENTYVIO. In September 2023, Takeda announced that the FDA has accepted for review its Biologics License Application (BLA) for the investigational subcutaneous formulation of ENTYVIO as a maintenance treatment for adults with moderately to severely active Crohn's disease, following induction therapy with the intravenous version of ENTYVIO. In April 2023, Takeda announced that the FDA has accepted for review its resubmitted Biologics License Application (BLA) for the investigational subcutaneous formulation of ENTYVIO as a maintenance treatment for adults with moderately to severely active ulcerative colitis following induction therapy with the intravenous version of ENTYVIO. In March 2023, Takeda announced that Japan's Ministry of Health, Labour, and Welfare has approved ENTYVIO Pens and prefilled syringes (108 mg for subcutaneous injection) for use as maintenance therapy in patients with moderate to severe ulcerative colitis. In May 2020, Takeda announced that the European Commission has approved the subcutaneous formulation of ENTYVIO, a gut-targeted biologic, for maintenance treatment in adults with moderately to severely active ulcerative colitis or Crohn's disease. In May 2019, Takeda announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved for an expanded indication of ENTYVIO, allowing its use in treating adult patients with moderately to severely active Crohn's disease. In May 2019, Takeda announced that the FDA has accepted for review the BLA for a SC formulation of vedolizumab, intended for maintenance treatment in adults with moderately to severely active ulcerative colitis. In November 2018, Takeda announced the launch of ENTYVIO in Japan for the treatment of patients with moderately to severely active ulcerative colitis. In June 2014, Takeda announced that ENTYVIO is now commercially available in the United States for treating adults with moderately to severely active ulcerative colitis or Crohn's disease. In May 2014, Takeda announced that the European Commission (EC) has granted Marketing authorization for ENTYVIO. It is the first and only biologic approved at the same time for treating adults with moderately to severely active ulcerative colitis and Crohn's disease who have not responded adequately to, lost response to, or were intolerant of conventional therapies or TNF-alpha inhibitors. In May 2014, Takeda announced that the FDA had granted simultaneous approval of ENTYVIO for the treatment of adults with moderately to severely active ulcerative colitis and Crohn's disease. Discover how ENTYVIO is shaping the Crohn's disease and ulcerative colitis treatment landscape @ ENTYVIO Infusion ENTYVIO Market Dynamics ENTYVIO has established itself as a leading biologic therapy in the treatment of moderate to severe ulcerative colitis and Crohn's disease. As a gut-selective integrin antagonist, ENTYVIO offers a differentiated mechanism of action compared to anti-TNF therapies, which contributes to its positioning as a safer long-term option, particularly for patients at risk of systemic immunosuppression. Its favorable safety profile and efficacy in inducing and maintaining remission have led to its widespread adoption, particularly among patients who have failed previous therapies. The biologics market for inflammatory bowel disease is highly competitive, with key players including HUMIRA, REMICADE, STELARA, and newer entrants like SKYRIZI and RINVOQ. ENTYVIO has managed to capture significant market share by appealing to both gastroenterologists and patients seeking gut-targeted treatment. Its intravenous formulation, though initially a barrier, has been partially offset by the 2019 launch of the subcutaneous version in global markets, enhancing patient convenience and adherence. However, uptake in the US for the SC version has been slower due to regulatory timelines and physician inertia. Biosimilar competition is also a factor shaping ENTYVIO's future market dynamics. While biosimilars of anti-TNFs are gaining traction, ENTYVIO currently remains insulated due to patent protections, with biosimilar entry expected post-2026. This provides Takeda a limited window to maximize revenue, expand its patient base, and reinforce brand loyalty. Strategic moves such as expanding indications, enhancing real-world evidence, and increasing global access will be crucial to maintaining its competitive edge. Moreover, the shift in payer dynamics and healthcare cost containment efforts are increasingly influencing biologic prescribing behavior. Takeda must continue to demonstrate value through outcome-based contracts and cost-effectiveness data. As newer agents with novel mechanisms enter the market, maintaining differentiation and proving long-term value will be central to ENTYVIO's sustained success. Dive deeper to get more insight into ENTYVIO's strengths & weaknesses relative to competitors @ ENTYVIO Market Drug Report Table of Contents Related Reports Crohn's Disease Market Crohn's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Crohn's disease companies including Novo Nordisk, Eli Lilly and Company, MedImmune, Boehringer Ingelheim, Raziel Therapeutics, Altimmune, Saniona, YSOPIA Bioscience, Innovent Biologics, Glaceum, Shionogi, Aardvark Therapeutics, NuSirt Biopharma, Novartis, CSPC Baike (Shandong) Biopharmaceutical, Jiangsu HengRui Medicine, Carmot Therapeutics, Pfizer, Sciwind Biosciences, Empros Pharma, among others. Crohn's Disease Pipeline Crohn's Disease Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Crohn's disease companies, including Janssen, RedHill Biopharma, Amgen, Pfizer, Prometheus Biosciences, AgomAb Therapeutics, Hoffmann-La Roche, Gilead Sciences, Eli Lilly and Company, Celgene, AstraZeneca, Mesoblast, Alfasigma, Tiziana Life Sciences, Abivax, Arena Pharmaceuticals, Cytocom, HAV Vaccines Ltd, Enzo Biochem Inc., Stero Biotechs, Reistone Biopharma Company Limited, Qu Biologics, Pfizer, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceuticals, Soligenix, Immunic, Pfizer, Atlantic Healthcare, 4D Pharma, Landos Biopharma, Janssen, Roche, Eisai, Bristol-Myers Squibb, Iltoo Pharma, Suzhou Connect Biopharmaceuticals, Theravance Biopharma, TaiwanJ Pharmaceuticals, Celularity, Cerecor, GlaxoSmithKline, KangStem Biotech, Immunic, Alpha Cancer Technologies, Koutif Therapeutics, Tract Therapeutics, Trio medicines, ChemoCentryx, Algernon Pharmaceuticals, Neuclone, JHL Biotech, Innovative Pharmacological Research (IPHAR) Co Ltd, Innovation Pharmaceuticals, Exeliom Biosciences SAS, AbbVie, Finch Therapeutics, Akeso Biopharma, Draconis Pharma, MakScientific, Engitix, Origo Biopharma, Navidea Biopharmaceuticals, Orchard Therapeutics, Xbrane, Thetis Pharmaceuticals, Temisis Therapeutics, Synedgen, Synlogic, Morphic Therapeutic, Metacrine, Curacle, Commence Bio Inc, Cloud Pharmaceuticals, Chong Kun Dang Pharmaceutical Corp, Avobis Bio LLC, Avexegen Therapeutics, Assembly Biosciences, Aibios Co Ltd, Aclaris Therapeutics, Athos Therapeutics, Denali Therapeutics, Educell doo, among others. Ulcerative Colitis Market Ulcerative Colitis Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the market trends, market drivers, market barriers, and key Ulcerative Colitis companies, including Eli Lilly and Company, Lipid Therapeutics, Hoffmann-La Roche, Arena Pharmaceuticals, InDex Pharmaceuticals, EA Pharma, Theravance Biopharma, Boehringer Ingelheim, Janssen Research & Development, Lycera, LG Chem, Iltoo Pharma, Immunic, Hutchison Medipharma, Tianjin Hemay Pharmaceutical, Celgene, among others. Ulcerative Colitis Pipeline Ulcerative Colitis Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Ulcerative Colitis companies, including Eli Lilly and Company, Lipid Therapeutics, Hoffmann-La Roche, Arena Pharmaceuticals, InDex Pharmaceuticals, EA Pharma, Theravance Biopharma, Boehringer Ingelheim, Janssen Research & Development, Lycera, LG Chem, Iltoo Pharma, Immunic, Hutchison Medipharma, Tianjin Hemay Pharmaceutical, Celgene, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期上市批准临床3期免疫疗法

2025-04-14

·医药速览

Nat. Rev. Drug. Disc. (IF 122.7) | 权威来袭！全面速览自免药物及靶点的最新趋势！

近日，Nature Reviews Drug Discovery期刊上发布了一篇名为《Trends in the drug target landscape for autoimmune diseases》的文章，主要探讨了自身免疫疾病药物靶点的最新趋势，特别是过去几年中行业研发管线的变化以及新兴治疗靶点的进展。文章标题该文的作者均来自Kearney的法国咨询团队，该团队基于Evaluate Pharma的数据，构建了一个包含已上市或处于临床开发阶段的免疫学药物的综合数据库。Kearney是一家全球管理咨询公司，与领先的制药企业开展合作。自身免疫疾病治疗的背景自身免疫疾病是由免疫失调导致的慢性炎症和组织损伤，涉及多个治疗领域，如皮肤科、风湿病学、胃肠病学、呼吸科、系统性疾病、神经学和感觉器官。通过调节细胞因子信号通路来靶向免疫系统，一直是过去25年自身免疫疾病治疗创新的核心。例如，肿瘤坏死因子（TNF）抑制剂（如英夫利昔单抗和阿达木单抗）已成为多种疾病的治疗标准。近年来，白细胞介素（IL）抑制剂和细胞因子受体下游信号通路中的酪氨酸激酶（如JAK）抑制剂也取得了成功。治疗靶点的现状该文分析了2024年处于临床II期和III期以及已上市的药物的前15个靶点，并与2020年的数据进行了比较。[早期试验（I期）、已放弃和暂停的临床试验不包含在分析范围内，主要是由于其创新的不确定性]免疫学领域行业研发管线及在研产品组合，按治疗靶点和开发阶段划分（浅蓝/深蓝/红色部分），为了反映多适应症药物的情况，如果一种药物针对多种疾病，则在同一个靶点下多次计数（紫色部分）。从上图可以看出，除CD40，CD40L靶点在临床II期的产品数量有所下降外，2024年其他研发管线产品相较于2020年，均呈现增加的趋势。新上市的药物自2020年以来，有四款first-in-class获批用于自身免疫疾病，其中三款针对皮肤疾病中的上皮屏障功能障碍和炎症（IL-13、IL-31和IL-36抑制剂），另一款是酪氨酸激酶2（TYK2）抑制剂，用于调节IL-12和IL-23的信号通路。行业研发管线的变化药物数量增长：在分析的92个治疗靶点中（见下表），从2020年到2024年，自身免疫疾病领域的药物研发数量从131个增加到193个（增长47%）。92个治疗靶点新靶点的进展：最显著的进展发生在针对肿瘤坏死因子超家族成员（非TNFα）的药物上：2020年，CD40/CD40L是唯一处于III期的此类靶点，而到2024年，针对OX40、TNF样配体1A（TL1A）、核因子κB受体激活因子（RANK）、B淋巴细胞刺激因子（BLyS）和B细胞激活因子（BAFF）的药物已进入III期试验。例如，TL1A抑制剂正在克罗恩病和溃疡性结肠炎中进行探索。IL靶向药物的创新：包括提高药物选择性（如IL-17A/F抑制剂）、延长药物作用时间（如GSK的长效IL-5抑制剂depemokimab）和新技术（如礼来的口服IL-17靶向小分子）。其他新兴靶点：如IL-4、IL-33和IL-18，以及与IL-1家族相关的IRAK4和TSLP、TYK2等。对不同疾病的影响皮肤疾病：2020年以来进展最大，推出了多种新药，如IL-13抑制剂（tralokinumab和lebrikizumab）、IL-17A/F选择性抑制剂（bimekizumab）、IL-31抑制剂（nemolizumab）和IL-36抑制剂（spesolimab）。风湿病：JAK抑制剂在强直性脊柱炎和类风湿关节炎等疾病中的应用不断扩大。胃肠道疾病：选择性JAK1抑制剂的使用增加，以及针对嗜酸性粒细食管炎的IL-4/IL-13靶向疗法。呼吸系统疾病：包括首个TSLP靶向药物tezepelumab用于重度哮喘，以及首个用于慢性阻塞性肺病（COPD）的生物制剂dupilumab。对于2型炎症性疾病（如特应性皮炎、慢性结节性痒疹、慢性荨麻疹、哮喘和慢性鼻窦炎伴鼻息肉）的竞争最为激烈。IL-5、效应细胞因子（IL-4、IL-13）、警报素细胞因子（TSLP、IL-25、IL-33）、IgE、IL-31、BTK和JAKs是关键靶点。未来创新的浪潮研发管线的动态性：预计未来几年将推出多种first-in-class疗法（见下图）。自身免疫疾病按治疗领域划分的II期和III期研发管线靶点格局演变（条形图显示了2020年和2024年按领域划分的选定疾病中特定靶点家族的相对比例）皮肤疾病：针对OX40/OX40L T细胞激活的新药（如Amgen的rocatinlimab和Sanofi的amlitelimab）有望成为关键上游调节因子。COPD：有望受益于针对IL-33的新疗法（如Sanofi的itepekimab和AstraZeneca的tozorakimab）。系统性疾病：CD40/CD40L可能为系统性疾病（如干燥综合征和系统性红斑狼疮）提供新的治疗选择（如Amgen的dazodalibep和Biogen/UCB的dapirolizumab）。炎症性肠病：针对TL1A的新药有望为克罗恩病和溃疡性结肠炎提供新的治疗选择（目前有三个候选药物：Merck的tulisokibart和Roche/Roivant的RVT-3101处于III期，Sanofi/Teva的duvakitug即将进入III期）。其他关键发现治疗靶点趋势分析：提取了2024年的前20个靶点，以了解免疫学领域的领先靶点和靶点家族，它们的开发成熟度阶段，以及与2020年的比较。免疫学领域行业研发管线及在研产品组合，按治疗靶点和开发阶段划分药物候选管线分析（按治疗领域和疾病）：评估了从2020年到2024年治疗选择的演变，基于药物数量和靶点家族的相对权重。关键自身免疫疾病按治疗领域划分的II期和III期研发管线靶点格局演变药物数量增长分析：从2020年到2024年，自身免疫疾病领域的药物管线和上市药物数量显著增加，新增了263种药物，增长约50%。其中，非生物类似药和非仿制药的增长占了大部分（65%），从2020年的315种增加到2024年的487种。按治疗领域和关键自身免疫疾病划分的药物数量概览靶点家族分析：TNF家族的药物数量最多，但其中大部分是生物类似药和仿制药。其他靶点家族如JAK家族和一些特定的白细胞介素靶点（如IL-12和IL-23组合）也有较多的生物类似药和仿制药。而其他靶点家族则很少有生物类似药和仿制药。按靶点家族和生物类似药/仿制药组合划分的靶点创新趋势靶点开发阶段分析：不同靶点家族和靶点的成熟度不同。例如，许多白细胞介素靶点已经有至少一种上市药物，而一些靶点组合（如IL-1和IRAK4，IL-13和TSLP，JAK1和BTK）也在开发中。2024年按靶点家族和开发阶段划分的靶点创新趋势2型炎症靶点的加速发展：研究特别关注了涉及2型炎症的免疫介质，包括IL-5、效应细胞因子（IL-4、IL-13）、警报素细胞因子（TSLP、IL-25、IL-33）、IgE以及额外的靶点如IL-31、酪氨酸激酶（BTK）和JAKs。与非2型炎症靶点相比，2型炎症靶点的管线增长显著加速。自2020年以来，上市适应症从79个增加到114个（+44%），而非2型靶点的增长为21%。二期管线的扩张更为迅速，增长了200%，而非2型靶点的增长为38%。总体而言，2型炎症靶点的适应症数量增长了67%，几乎是其他靶点增长的两倍（32%）。2型炎症与其他靶点的创新趋势对比行业面临的挑战和未来方向疾病特异性机制：自身免疫疾病领域正在从广泛的炎症级联反应转向针对特定疾病的机制。药物定位的复杂性：包括临床试验中治疗比较选择、联合疗法和生物标志物驱动的患者细分。市场竞争：包括对first-in-class药物（如TL1A、OX40、TSLP、IL-33和TYK2）的竞争，以及对best-in-class药物（如IL-17、IL-23和JAK抑制剂）的竞争。总结该文章强调，这些进展标志着自身免疫疾病管理的新纪元，制药行业需要在药物设计、靶点选择性和治疗方案的便利性方面不断创新，以满足患者需求并应对市场竞争。常见知识点供给站：“First-in-class”（首创新）：指的是某一类药物中的第一个具有独特作用机制的药物。这种药物的作用机制在同类药物中是全新的，与现有的其他药物不同。“Best-in-class”（同类最佳）：指的是在某一类药物或产品中表现最为出色、具有最佳疗效或性能的药物或产品。与“first-in-class”（首创新）不同，“best-in-class”药物不一定是最先上市的，但通常是现有药物中效果最好、安全性最高或使用最方便的。详细信息请点击下方“阅读原文”推文用于传递知识，如因版权等有疑问，请于本文刊发30日内联系医药速览。原创内容未经授权，禁止转载至其他平台。有问题可发邮件至yong_wang@pku.edu.cn获取更多信息。©2021 医药速览保留所有权利往期链接“小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记PROTAC技术| 抗体药物| 抗体药物偶联-ADC核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

临床2期临床3期免疫疗法临床结果上市批准

100 项与 Tulisokibart 相关的药物交易

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研发状态

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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	鹹築壓鹽艱憲夢顧簾鏇(壓製構顧積鏇範製顧餘) = 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. 簾壓壓顧襯鹹齋襯淵製 (積艱積衊遞簾鏇餘網觸 )	-	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	築觸選餘壓顧餘範憲繭(遞獵獵醖糧窪憲艱構積) = 齋範鹹廠衊製鬱醖衊鑰衊窪餘遞鬱夢齋夢遞構 (窪窪網鬱繭衊淵鬱繭窪 )	积极	2024-09-26
				Placebo	築觸選餘壓顧餘範憲繭(遞獵獵醖糧窪憲艱構積) = 蓋齋繭壓築餘構繭觸鹽衊窪餘遞鬱夢齋夢遞構 (窪窪網鬱繭衊淵鬱繭窪 )
NCT04996797 (ARTEMIS-UC, CTgov)	临床2期	溃疡性结肠炎	178	Tulisokibart (Cohort 1 Tulisokibart)	蓋簾積繭艱鑰醖繭製蓋 = 艱鏇築鏇繭憲衊鏇膚膚遞廠選鏇網艱選繭積鹽 (蓋鑰廠艱築憲淵鏇觸觸, 簾憲選鏇壓艱築製衊廠 ~ 壓壓簾廠遞簾襯築糧鏇) 更多	-	2024-06-27
				Placebo (Cohort 1 Placebo)	蓋簾積繭艱鑰醖繭製蓋 = 鹽繭壓製繭範襯夢膚獵遞廠選鏇網艱選繭積鹽 (蓋鑰廠艱築憲淵鏇觸觸, 齋簾夢構築夢襯憲窪築 ~ 鬱顧鹽醖繭夢艱選鹽醖) 更多
NCT05013905 (APOLLO-CD, CTgov)	临床2期	克罗恩病	55	Companion diagnostic (CDx)+PRA023 IV	簾鑰遞鏇膚窪網齋憲衊 = 製鏇築齋鹹鏇齋觸選艱壓鬱醖衊選積鏇壓觸鹹 (願繭壓夢憲淵築積積遞, 選製膚積顧簾餘網鬱網 ~ 製蓋餘鏇窪鏇獵窪鹹壓) 更多	-	2023-11-01
ARTEMIS-UC \| COHORT 1 (UEGW2023)	临床2期	活动性中度溃疡性结肠炎 TL1A	135	PRA023	鬱襯淵網鏇鏇鑰衊糧艱(簾餘艱鑰顧餘構鬱簾觸) = 顧壓願餘網膚窪襯網網衊衊齋糧選顧鏇鹹遞艱 (鹽醖壓窪糧餘選壓築艱 ) 更多	积极	2023-10-15
				Placebo	鬱襯淵網鏇鏇鑰衊糧艱(簾餘艱鑰顧餘構鬱簾觸) = 遞鏇憲顧鬱遞廠蓋網積衊衊齋糧選顧鏇鹹遞艱 (鹽醖壓窪糧餘選壓築艱 ) 更多
NCT04996797 (ARTEMIS-UC, UEGW2023)	临床2期	活动性中度溃疡性结肠炎 eosinophils \| neutrophils	135	PRA023	製範遞襯壓積遞繭鹹構(簾選選齋憲齋壓積鑰鹽) = 鹽遞築憲顧艱膚鏇艱獵鹽簾艱願憲選窪餘獵鹹 (憲網衊鬱範襯糧膚獵壓 ) 更多	积极	2023-10-15
				Placebo	製範遞襯壓積遞繭鹹構(簾選選齋憲齋壓積鑰鹽) = 蓋構製繭窪窪簾積鏇衊鹽簾艱願憲選窪餘獵鹹 (憲網衊鬱範襯糧膚獵壓 ) 更多
UEGW2023	N/A	活动性中度溃疡性结肠炎	-	PRA023	蓋窪糧襯構糧製觸積鹽(餘顧廠襯鑰鑰艱廠繭網) = 衊鹽蓋網繭願壓廠壓艱獵鏇願窪構夢簾網積蓋 (衊醖壓繭網醖簾製築廠, 34.85) 更多	-	2023-10-15
				Placebo	蓋窪糧襯構糧製觸積鹽(餘顧廠襯鑰鑰艱廠繭網) = 網鑰鑰淵醖襯觸艱鑰齋獵鏇願窪構夢簾網積蓋 (衊醖壓繭網醖簾製築廠, 37.59) 更多