A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects with Moderate to Severe Ulcerative Colitis - FIGARO UC 302

开始日期2019-11-01

申办/合作机构

Shire Human Genetic Therapies, Inc.

NCT03559517

/ Terminated临床3期

A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 305)

The purpose of this study is to evaluate the efficacy and safety of ontamalimab in inducing clinical remission and endoscopic response in participants with moderate to severe Crohn's Disease.

开始日期2018-08-29

申办/合作机构

Shire Plc

NCT03566823

/ Terminated临床3期

A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn's Disease (CARMEN CD 306)

The purpose of this study is to evaluate the efficacy and safety of Ontamalimab in inducing clinical remission and endoscopic response in participants with moderate to severe Crohn's Disease.

开始日期2018-07-17

申办/合作机构

Shire Plc

100 项与 Ontamalimab 相关的临床结果

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100 项与 Ontamalimab 相关的转化医学

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100 项与 Ontamalimab 相关的专利（医药）

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项与 Ontamalimab 相关的文献（医药）

2024-05-31·Journal of Crohn's & colitis

Efficacy and Safety of the Anti-mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn’s Disease

Article

作者: Schreiber, Stefan ; Cataldi, Fabio ; Gorelick, Kenneth J ; D’Haens, Geert ; Reinisch, Walter ; Thakur, Manoj ; Sandborn, William J ; Goetsch, Martina ; Nagy, Peter ; Hanauer, Stephen ; Bliss, Caleb ; Vermeire, Séverine ; Danese, Silvio

Abstract:

Background and Aims:

Ontamalimab is a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, developed as treatment for inflammatory bowel disease.

Methods:

Six phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trials compared efficacy and safety of ontamalimab [25 mg and 75 mg once every 4 weeks] with placebo in patients with moderate-to-severe ulcerative colitis or Crohn’s disease [two induction studies and one re-randomised maintenance study per condition]. This clinical trial programme was discontinued in 2020 for reasons unrelated to drug safety/efficacy; Crohn’s disease studies are described in the Supplementary data.

Results:

The induction [12-week] and maintenance [52-week] studies included 659 and 366 randomised patients, respectively. More patients who received ontamalimab induction than placebo achieved the primary endpoint of clinical remission at Week 12 [25 mg, 18.5% vs 15.8%, p = 0.617, 27.0% vs 12.5%, p = 0.027; 75 mg, 29.8% vs 15.8%, p = 0.018, 29.5% vs 12.5% p = 0.014]; significantly more patients who received ontamalimab maintenance therapy than placebo achieved Week 52 clinical remission [25 mg, 53.5% vs 8.2%, p <0.001; 75 mg, 40.2% vs 12.8%, p <0.001]. Endoscopic improvement was generally significantly different vs placebo [induction: 25 mg, 27.8% vs 21.1%, p = 0.253, 35.1% vs 12.5%, p = 0.001; 75 mg, 41.1% vs 21.1%, p = 0.002, 33.9% vs 12.5%, p = 0.003; maintenance: 25 mg, 56.3% vs 9.6%, p <0.001; 75 mg, 48.8% vs 15.1%, p <0.001]. Adverse event rates were similar between ontamalimab and placebo groups.

Conclusions:

Ontamalimab 75 mg was effective, with no safety concerns, as induction and maintenance therapy for patients with moderate-to-severe ulcerative colitis. [NCT03259334; NCT03259308; NCT03290781; NCT03559517; NCT03566823; NCT03627091]

2024-04-01·Drug safety

Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis

Review

作者: Sarmati, Loredana ; Malagnino, Vincenzo ; Iannetta, Marco ; Rindi, Lorenzo Vittorio ; Fato, Ilenia ; Zaçe, Drieda ; Kontogiannis, Dimitra ; Barchi, Virginia ; Iannazzo, Roberta ; Braccialarghe, Neva ; De Maria, Francesco ; Massa, Barbara

INTRODUCTION:

Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus (HIV) epidemic, people living with HIV have represented most cases for more than a decade. With the diffusion of highly active antiretroviral therapy, this group progressively decreased in favor of patients undergoing treatment with targeted therapy/immunomodulators. In this systematic review and meta-analysis, the objective was to assess which drugs are most frequently related to PML development, and report the incidence of drug-induced PML through a meta-analytic approach.

METHODS:

The electronic databases MEDLINE, EMBASE, ClinicalTrials.gov, Web of Science and the Canadian Agency for Drugs and Technologies in Health Database (CADTH) were searched up to May 10, 2022. Articles that reported the risk of PML development after treatment with immunomodulatory drugs, including patients of both sexes under the age of 80 years, affected by any pathology except HIV, primary immunodeficiencies or malignancies, were included in the review. The incidence of drug-induced PML was calculated based on PML cases and total number of patients observed per 100 persons and the observation time. Random-effect metanalyses were conducted for each drug reporting pooled incidence with 95% confidence intervals (CI) and median (interquartile range [IQR]) of the observation time. Heterogeneity was measured by I² statistics. Publication bias was examined through funnel plots and Egger's test.

RESULTS:

A total of 103 studies were included in the systematic review. In our analysis, we found no includible study reporting cases of PML during the course of treatment with ocrelizumab, vedolizumab, abrilumab, ontamalimab, teriflunomide, daclizumab, inebilizumab, basiliximab, tacrolimus, belimumab, infliximab, firategrast, disulone, azathioprine or danazole. Dalfampridine, glatiramer acetate, dimethyl fumarate and fingolimod show a relatively safe profile, although some cases of PML have been reported. The meta-analysis showed an incidence of PML cases among patients undergoing rituximab treatment for multiple sclerosis (MS) of 0.01 cases/100 persons (95% CI - 0.08 to 0.09; I² = 20.4%; p = 0.25) for a median observation period of 23.5 months (IQR 22.1-42.1). Treatment of MS with natalizumab carried a PML risk of 0.33 cases/100 persons (95% CI 0.29-0.37; I² = 50%; p = 0.003) for a median observation period of 44.1 months (IQR 28.4-60) and a mean number of doses of 36.3 (standard deviation [SD] ± 20.7). When comparing data about patients treated with standard interval dosing (SID) and extended interval dosing (EID), the latter appears to carry a smaller risk of PML, that is, 0.08 cases/100 persons (95% CI 0.0-0.15) for EID versus 0.3 cases/100 persons (95% CI 0.25-0.34) for SID.

CONCLUSIONS:

A higher risk of drug-related PML in patients whose immune system is not additionally depressed by means of neoplasms, HIV or concomitant medications is found in the neurological field. This risk is higher in MS treatment, and specifically during long-term natalizumab therapy. While this drug is still routinely prescribed in this field, considering the efficacy in reducing MS relapses, in other areas it could play a smaller role, and be gradually replaced by other safer and more recently approved agents.

2023-11-24·Journal of Crohn's & colitis

Differential Effects of Ontamalimab Versus Vedolizumab on Immune Cell Trafficking in Intestinal Inflammation and Inflammatory Bowel Disease

Article

作者: Kirchner, Philipp ; Ekici, Arif B ; Schulze, Lisa Lou ; Wiendl, Maximilian ; Müller, Tanja M ; Sexton, Dan ; Liu, Li-Juan ; Leppkes, Moritz ; Dedden, Mark ; Stürzl, Michael ; Neurath, Markus F ; van Passen, Chiara ; Palliser, Deborah ; Atreya, Raja ; Siegmund, Britta ; Becker, Emily ; Atreya, Imke ; Ullrich, Karen A M ; Zundler, Sebastian ; Mohamed-Abdou, Mariam

Abstract:

Background and Aims:

The anti-MAdCAM-1 antibody ontamalimab demonstrated efficacy in a phase II trial in ulcerative colitis and results of early terminated phase III trials are pending, but its precise mechanisms of action are still unclear. Thus, we explored the mechanisms of action of ontamalimab and compared it to the anti-α4β7 antibody vedolizumab.

Methods:

We studied MAdCAM-1 expression with RNA sequencing and immunohistochemistry. The mechanisms of action of ontamalimab were assessed with fluorescence microscopy, dynamic adhesion and rolling assays. We performed in vivo cell trafficking studies in mice and compared ontamalimab and vedolizumab surrogate [-s] antibodies in experimental models of colitis and wound healing. We analysed immune cell infiltration under anti-MAdCAM-1 and anti-α4β7 treatment by single-cell transcriptomics and studied compensatory trafficking pathways.

Results:

MAdCAM-1 expression was increased in active inflammatory bowel disease. Binding of ontamalimab to MAdCAM-1 induced the internalization of the complex. Functionally, ontamalimab blocked T cell adhesion similar to vedolizumab, but also inhibited L-selectin-dependent rolling of innate and adaptive immune cells. Despite conserved mechanisms in mice, the impact of ontamalimab-s and vedolizumab-s on experimental colitis and wound healing was similar. Single-cell RNA sequencing demonstrated enrichment of ontamalimab-s-treated lamina propria cells in specific clusters, and in vitro experiments indicated that redundant adhesion pathways are active in these cells.

Conclusions:

Ontamalimab has unique and broader mechanisms of action compared to vedolizumab. However, this seems to be compensated for by redundant cell trafficking circuits and leads to similar preclinical efficacy of anti-α4β7 and anti-MAdCAM-1 treatment. These results will be important for the interpretation of pending phase III data.

项与 Ontamalimab 相关的新闻（医药）

2024-05-14

·药精通Bio

武田年报终止项目一览

深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，7月相约苏州，联系电话181 1603 6798日企财报年通常从4月起计。昨天武田公布了2023财年的年度报告。武田利润的急剧下滑，原因包括一些畅销和高利润药物（例如多动症药物 Vyvanse）的专利最近到期，给公司的财务带来压力。武田预计下一个财年投入约 9 亿美元的重组成本扭转局面。公司目标是从 2025 年起每年将核心营业利润率提高 1% 至 2.5%，最终目标在 30%。武田首席执行官 Christophe Weber 在一份公司声明中表示：“展望 2024 财年，我们预计将有6个项目处于3期开发中。” “通过后期开发推进这些有前景的疗法，同时适度增加我们的生物制药研发投资，需要严格的优先顺序、效率和组织敏捷性。”共有 18 个药物项目现已从1期或2期研究中剔除，尽管 TAK-007 等一些项目将继续在其他适应症中开发。这比 2 月份的演示中列出的 11 个项目有所增加。有三个临床中期的癌症疗法被终止：TAK-573（Modakafusp Alfa）、TAK-981（subasumstat）和细胞疗法 TAK-007。TAK-573（Modakafusp Alfa）是一款first-in-class的免疫靶向减毒细胞因子，将减毒干扰素α-2b(IFNα2b)片段递送至表达CD38肿瘤细胞，有潜力在保证安全性的同时提高疗效，曾被寄予希望。但2月份武田已宣布终止了该项目。小分子sumo抑制剂TAK-981（subasumstat）也被终止。武田研发总裁Andrew Plump在年初筛选了若干有前景的癌症药物时将该分子列为值得关注的候选分子。三个月后TAK-981 作为“当前可用数据和临床开发时间表”确定的优先事项的一部分被终止。武田于 1 月份以入组挑战为由终止了一项血癌试验，并于 3 月份停止了一项远未达到目标的实体瘤研究的招募。CD19 CAR-T疗法TAK-007做出了“数据驱动的决定，停止了 CD19 CAR-NK 细胞治疗 B 细胞恶性肿瘤的临床开发”，但该项目在自身免疫性疾病方面的工作将继续进行。武田还削减了其他项目。TAK-079（mezagitamab）是一种抗 CD38 抗体，此次终止了用于治疗重症肌无力和系统性红斑狼疮的开发。但仍计划在 2024 财年启动治疗原发性免疫性血小板减少症的 3 期试验。用于恶心和呕吐的候选药物 TAK-951 也被淘汰，在其临床数据未达到支持进一步开发所需的标准。TAK-647 是武田在收购 Shire 时获得的一种抗 MAdCAM-1 抗体。Shire 于 2016 年从辉瑞公司获得了该分子的许可，并投入克罗恩病和溃疡性结肠炎的 3 期试验。武田本应剥离该资产，但最终未能找到买家，炎性肠炎的适应症开发失败。而后武田将该抗体作为一种潜在的MASH疗法开发，但作为此次投资组合优先顺序的一部分武田停止了开发。END深度聚焦多肽、多肽偶联药物研发、质控、工艺开发，7月相约苏州，联系电话18116036798戳“阅读原文”立即报名多肽药物论坛吧!

财报细胞疗法免疫疗法临床3期并购

2024-05-11

·生物制药小编

武田关闭一家研发中心

近日，根据外媒Endpoints的报道，武田制药将关闭其在加州圣地亚哥研发中心。这家研发中心是2019年建立的，功能方面是用于弥补旧有研发基地的不足的。该公司发言人称，该中心的关闭是更大战略下重组的一部分，为了让公司更好地集中在其他更有前途的后期管线上，并对员工进行优化。武田拒绝就关闭工厂的时间表或可能受到影响的工作岗位数量置评。该公司表示，目前约有340名全职员工在该基地工作，一些员工将被调往马萨诸塞州剑桥市和日本湘南市（日本神奈川县相模湾北部沿海地区）的其他研究基地。虽然不清楚该研发中心具体和那些管线有关，但是之前其实该公司的管线裁撤事件已有预兆。裁撤多条管线的武田根据这家公司此前发布的2023年Q4财报显示，截至2024年3月31日的财年，武田收入超过270亿美元。这一数字比其2023财年258亿美元的收入增长了1.5%。尽管收入大幅增长，但武田公司今年的净利润下降了57%，至9.25亿美元，而上一财年的净利润约为20亿美元。武田报告的营业利润同样遭受了50.3%的打击，在2023财年从31.5亿美元降至13.7亿美元。而为了应对这一问题，重组和裁员是必不可少的，管线的裁撤也不例外。展望2024财年的剩余时间，武田甚至降低了投资者的预期，并将核心运营利润指引下调了约10%。而2023整个年度，该公司线一连砍去了24款管线的不同项目，其中不乏已经推进到II、III临床的管线的适应症放弃，还有一些是管线整体的裁撤。而即便从被完全裁撤的I期临床项目来看，这个数量也相当惊人例如，TAK-920/DNL919，TAK-103，TAK-102，TAK-940，TAK-426，TAK-647等等。考虑到2019年这个微妙的时间节点（武田在2019年收购了夏尔，顺便获得了数条来自夏尔的管线），可能与研发中心关闭相关联的是一些I期临床。TAK-920/DNL919看到DNL的前缀就知道这是武田和Denali公司（也在加州）合作的产物，技术上采用的是通过抗体运输工具（ATV）将TREM2抗体递送到脑内。通过激活TREM2，DNL-919旨在增强小胶质细胞的吞噬作用和免疫响应，从而改善阿尔茨海默病患者大脑中的病理状态和认知功能。不过显然这项在2021年签订的合作项目在选择阿尔兹海默症作为适应症就注定需要遇到难题。实际上这款药物临床前独立评估的时候，就没通过FDA的毒理学评估被搁置了。虽然后来又在2022年7月正式进入了临床，但2023年8月问题再度出现。研究在测试的最高剂量下观察到了中度、可逆血液学影响的安全信号，这表明TAK-920/DNL919的治疗窗口很狭窄：这其实可能表明TREM2在低剂量下，可能没什么效果，而高剂量安全问题就浮现了。因此就被放弃了。TAK-102（NIB-102）和TAK-103（NIB-103）TAK-102和TAK-103都是由同样是日本公司Noile-Immune Biotech授权给武田的，时间点是2017年，TAK-102开发方向是GPC3-CAR-T的实体瘤，而TAK-103的开发方向则是MSLN-CAR-T的实体瘤。因为同样是日本公司，临床设立在日本，似乎没有必要特意去美国开设一个研发中心，TAK-102和TAK-103的研发项目应该和此次研发中心关闭无关。不过即便如此，TAK-102和103仍然值得一窥。技术上来看，Noile-Immune Biotech两款管线的裁撤相对合理，他们采用的是能够分泌CCL19和IL7的CAR-T结构，想要利用IL-7促进T细胞的生长和存活，利用CCL19增强T细胞和树突细胞的迁移，当然想法很美好，实际临床验证是另外一回事。实际上2022年时Noile-Immune Biotech就被传奇生物退货，这可能是对于这家日本药企技术的不认可。TAK-940TAK-940是和纪念斯隆-凯特琳癌症中心合作的项目。根据ASH上的报道，TAK-940是血液瘤方向上开发的CD19-CAR-T，这种新的CAR-T选用优化的1XX信号结构域替代天然CD3ζ免疫受体基于酪氨酸的激活基序。这种1XX设计延长了CAR T细胞的功能持久性，并增加了小鼠体内的效力。而在临床试验中，这一CD19-CAR-T似乎在CD57和激活标记TIM3的表达上有所增加，而CD57表达与衰老表型相关，TAK-940是否能够做到提高持久性要打个疑问。因此被裁撤似乎也相当合理。TAK-647（SHP647，Ontamalimab，PF-00547659）TAK-647是一种抗MAdCAM-1抗体，机理上与炎症疾病有关，最初由辉瑞开发。后来授权给夏尔，而夏尔被收购时就被武田获得。MAdCAM-1是一种主要表达在胃肠道和其它粘膜组织血管内皮细胞上的粘附分子，它在淋巴细胞向肠道炎症区域的迁移过程中起着关键作用。通过特异性结合MAdCAM-1，TAK-647能够阻止这些淋巴细胞迁移到炎症部位，从而减轻炎症性肠病（Inflammatory Bowel Disease, IBD）。尽管机理如此，但是在克罗恩病中的开发并没有成功，后续的研究表明，疗效不起作用似乎是因为有细胞运输的补偿通路存在，所以TAK-647并不能尽善尽美地实现疗效，反而可能会抑制先天免疫……后来武田又想要用这种药物去开发NASH，考虑到目前GLP-1以及NASH领域已有先发者优势的情况，放弃TAK-647具有一定合理性。总结总的来说，近日日元走弱的趋势对于日本药企的影响也可能在2024年展现出来，只是不清楚对武田的影响会有多大。武田可能将成为一个这一特殊背景下的案例。研发中心的关闭具有一定合理性。参考来源：https://www.fiercebiotech.com/biotech/takeda-denali-drop-alzheimers-asset-after-phase-1-peak-reveals-narrow-therapeutic-windowhttps://ashpublications.org/blood/article/142/Supplement%201/349/503114/Role-of-Cell-Therapy-Product-Characteristics-inSchulze LL, Becker E, Dedden M, Liu LJ, van Passen C, Mohamed-Abdou M, Müller TM, Wiendl M, Ullrich KAM, Atreya I, Leppkes M, Ekici AB, Kirchner P, Stürzl M, Sexton D, Palliser D, Atreya R, Siegmund B; TRR241 IBDome consortium; Neurath MF, Zundler S. Differential Effects of Ontamalimab Versus Vedolizumab on Immune Cell Trafficking in Intestinal Inflammation and Inflammatory Bowel Disease. J Crohns Colitis. 2023 Nov 24;17(11):1817-1832. doi: 10.1093/ecco-jcc/jjad088. PMID: 37208197.

财报并购高管变更

2024-02-10

·精准药物

MAdCAM-1，下一个FIC药物的关键靶点

PREFACE前言MAdCAM-1（粘膜血管地址素细胞粘附分子1）是一种内皮细胞粘附分子，在免疫系统中发挥关键作用。它主要存在于肠道黏膜血管内皮细胞表面，可以结合免疫细胞表面的α4β7整合素，从而促使免疫细胞（如淋巴细胞）定向迁移到肠道黏膜，介导炎症反应。关于MAdCAM-1靶点的研究在免疫学和炎症性肠病领域具有重要意义。MAdCAM-1的结构和域结构示意图（https://www.proteinatlas.org）01MAdCAM-1靶点与疾病研究1. MAdCAM-1与肠粘膜炎症MAdCAM-1在肠粘膜和肠相关淋巴组织的内皮细胞中选择性表达。MAdCAM-1可以结合表达其配体整合素α4β的淋巴细胞，促使肠道相关淋巴细胞归巢至正常胃肠道和炎症部位。在炎症性肠病（IBD）治疗领域，针对MAdCAM-1的研究已经取得一些进展。一些药物已经针对MAdCAM-1进行了设计，用于治疗类风湿性关节炎、克罗恩病和溃疡性结肠炎等疾病。这些药物通过抑制MAdCAM-1与α4β7整合素的结合，从而减少免疫细胞对肠道黏膜的定向迁移，从而减轻炎症性肠病的症状。2. MAdCAM-1与肠道免疫调节此外，研究人员也在探索MAdCAM-1在肠道免疫调节中的作用，并进一步挖掘与其他疾病（如自身免疫性疾病和肠道肿瘤）的关联，对MAdCAM-1的深入研究有望为相关疾病的治疗提供新的靶点和治疗方法。如Fidelle等研究表明，在接受抗生素治疗的小鼠的肠道中，肠梭菌会下调MAdCAM-1的表达水平。然而MAdCAM-1是整合素α4β7的配体，有助于在肠道内浸润Treg 17 细胞，这会导致Treg 17细胞转运至肿瘤和肿瘤引流淋巴结，从而损害免疫检查点阻断治疗。高表达MAdCAM-1的肠道内皮细胞招募α4β7+的Treg17细胞浸润（来源doi:10.1126/science.abo2296）随着对MAdCAM-1的进一步研究，我们有望更深入地了解其在免疫系统中的作用，并为相关疾病的治疗带来新的突破。 02MAdCAM-1靶点相关临床药物随着对MAdCAM-1的进一步研究，我们有望更深入地了解其在免疫系统中的作用，并为相关疾病的治疗带来新的突破。临床药物目前，已经有一些针对MAdCAM-1的靶向药物正处于临床前研发阶段，用于治疗多种疾病，包括类风湿性关节炎、克罗恩病和溃疡性结肠炎等炎症性疾病。1.维得利珠单抗（Vedolizumab）维得利珠单抗是一种抗体药物，可特异性地抑制MAdCAM-1与α4β7整合素的结合，从而阻止免疫细胞定向迁移到肠道黏膜，缓解炎症性肠病的症状。Timothy Springer教授于1993年创立LeukoSite，成功研发出维得利珠单抗。后LeukoSite公司于1999年被Millennium以6.35亿美元收购，该药物并最终由武田制药开发上市（2008年武田收购Millennium）。2014年5月20日，美国FDA批准维多珠单抗用于治疗中重度溃疡性结肠炎和克罗恩病。一周后，维多珠单抗也获得欧洲FDA批准，委托用于相同的适应症。当一种或多种标准疗法（如皮质类固醇、免疫调节剂或肿瘤坏死因子阻断药物）无法获得充分的治疗效果，推荐使用维多珠单抗。成人主要在肠道脉管系统和肠道相关的次级淋巴器官中表达MAdCAM-1，在炎症性肠病患者中，MAdCAM-1高表达。MAdCAM-1虽也由其它少数组织表达，但水平较低。因此，α4β7和MAdCAM-1之间的相互作用对肠道具有高度特异性，维得利珠单抗不会影响胃肠道外组织中的免疫细胞运输，因此是现有的较安全的生物制剂。在III期试验中，维多珠单抗已被证明是有效和安全的。2.SHP647（Ontamalimab，PF-00547659）SHP647是由辉瑞研发的针对内皮细胞上的MAdCAM-1的全人单克隆抗体，具有高亲和力和选择性，可阻止α4β7+淋巴细胞与胃肠道高内皮微静脉中MAdCAM-1表达位点的结合。SHP647不与细胞间粘附分子-1或血管细胞粘附分子-1结合，因此不会影响中枢神经系统中的淋巴细胞归巢和免疫监视。并且根据已有研究，SHP647可以在体外抑制表达α4β的细胞与MAdCAM-1的粘附。目前，SHP647正在开发用于治疗溃疡性结肠炎（UC）和克罗恩（CD）。在针对UC和CD的II期研究中，SHP647的耐受性良好。在一项针对中重度UC患者的临床试验中，结果显示：与安慰剂组相比，治疗组在第12周的缓解率显著较高。此外，SHP647表现出良好的耐受性和良好的安全性。评估 SHP647 对 UC 和 CD 的有效性和安全性的III期研究正在进行中。SUMMARY小结此外，还有其他一些药物处于研究和临床试验阶段，以探索其针对MAdCAM-1的疗效，而这些药物的研究可能会为未来的炎症性疾病治疗提供更多选择。总的来说，MAdCAM-1的靶向药物及相关研究正朝着为治疗炎症性疾病，尤其是免疫相关肠道疾病，提供更有效的治疗方法迈进。相关产品链接ACROBiosystems百普赛斯为助力炎症性肠病（IBD）药物发展，针对Integrin α4β7重要配体，溃疡性结肠炎 (UC) 和克罗恩病 (CD) 重要靶点MAdCAM-1开发了高品质抗体药物开发工具MAdCAM-1重组蛋白，高纯度经SEC-MALS、SDS-PAGE验证＞95%，高生物活性经SPR、ELISA验证，产品多标签，生物素标记，批间一致性高，适用于免疫、抗体筛选、CMC质控放行等。除MAdCAM-1蛋白外，ACROBiosystems百普赛斯采用竞争ELISA方法，建立了抑制剂筛选平台，利用独特的生物素化MAdCAM-1 蛋白，开发了高质量Integrin α4β7 : MAdCAM-1 [Biotinylated] 抑制剂筛选试剂盒，可用于前期筛选以及QC质控放行。点击文章底部“阅读原文”获取产品链接参考文献[1] Arihiro S, Ohtani H, Suzuki M, et al. Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Pathol Int. 2002;52(5-6):367-374.[2] Fidelle M, Rauber C, Alves Costa Silva C, et al. A microbiota-modulated checkpoint directs 5immunosuppressive intestinal T cells into cancers. Science. 2023;380(6649):eabo2296.[3] Colombel JF, Sands BE, Rutgeerts P, et al. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017;66(5):839-851.[4]Singh, Harmanjit et al.“Vedolizumab: A novel anti-integrin drug for treatment of inflammatory bowel disease.”Journal of natural science, biology, and medicine vol. 7,1 (2016): 4-9.[5] Allocca M, Gilardi D, Fiorino G, et al. PF-00547659 for the treatment of Crohn's disease and ulcerative colitis. Expert Opin Investig Drugs. 2018;27(7):623-629.[6] Reinisch W, Hung K, Hassan-Zahraee M, Cataldi F. Targeting Endothelial Ligands: ICAM-1/alicaforsen, MAdCAM-1. J Crohns Colitis. 2018;12(suppl_2):S669-S677.[7]Jairath, Vipul et al.“Alicaforsen for the treatment of inflammatory bowel disease.”Expert opinion on investigational drugs vol. 26,8 (2017): 991-997.声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

并购临床结果引进/卖出临床研究免疫疗法

100 项与 Ontamalimab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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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	Shire Plc	2018-02-27
克罗恩病	临床3期	日本	Shire Plc	2018-02-27
克罗恩病	临床3期	阿根廷	Shire Plc	2018-02-27
克罗恩病	临床3期	澳大利亚	Shire Plc	2018-02-27
克罗恩病	临床3期	奥地利	Shire Plc	2018-02-27
克罗恩病	临床3期	比利时	Shire Plc	2018-02-27
克罗恩病	临床3期	波斯尼亚和黑塞哥维那	Shire Plc	2018-02-27
克罗恩病	临床3期	保加利亚	Shire Plc	2018-02-27
克罗恩病	临床3期	加拿大	Shire Plc	2018-02-27
克罗恩病	临床3期	哥伦比亚	Shire Plc	2018-02-27

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临床结果

适应症

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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


NCT03566823 \| NCT03290781 \| NCT03259334 \| NCT03559517 \| NCT03259308 \| NCT03627091 (Pubmed)	临床3期	活动性重度克罗恩病 \| 溃疡性结肠炎维持	-	Ontamalimab 25 mg	艱醖鏇觸衊觸廠廠壓鬱(製淵襯願壓鹹衊選淵觸) = 窪糧窪齋夢艱鹽網遞顧遞鏇糧艱淵蓋廠壓選鹹 (築餘鏇鹽窪衊壓遞繭壓 ) 更多	积极	2023-12-14
				Ontamalimab 75 mg	艱醖鏇觸衊觸廠廠壓鬱(製淵襯願壓鹹衊選淵觸) = 鹽鏇齋鏇繭憲衊衊鹽齋遞鏇糧艱淵蓋廠壓選鹹 (築餘鏇鹽窪衊壓遞繭壓 ) 更多
NCT03627091 (CARMEN CD 307, CTgov)	临床3期	克罗恩病	40	Placebo (Placebo)	糧鹽壓積艱窪範簾網範 = 鬱鹽製築窪選繭糧顧艱餘艱壓餘衊憲繭獵齋壓 (壓繭餘範構齋簾獵艱簾, 築鹹製廠鹽製壓獵獵選 ~ 鹽廠膚糧鏇齋窪鏇齋觸) 更多	-	2022-03-31
				Ontamalimab (Ontamalimab 25 mg)	糧鹽壓積艱窪範簾網範 = 願鹹鹹選壓餘窪襯構襯餘艱壓餘衊憲繭獵齋壓 (壓繭餘範構齋簾獵艱簾, 顧顧遞廠製窪構觸鑰淵 ~ 衊窪製憲餘糧遞顧廠簾) 更多
NCT03290781 (FIGARO UC 303, CTgov)	临床3期	溃疡性结肠炎	366	ONTA (ONTA 25 mg/ Placebo)	鹽獵願鑰顧廠蓋鹹範範 = 構製餘餘觸製鑰齋築醖獵壓築網夢艱遞積膚醖 (願製淵膚顧繭壓壓糧醖, 築憲選餘廠簾觸網窪餘 ~ 醖顧鹹餘繭鏇窪襯齋窪) 更多	-	2022-01-14
				ONTA (ONTA 25 mg/ONTA 25 mg)	鹽獵願鑰顧廠蓋鹹範範 = 鹹衊膚構艱蓋衊糧鏇夢獵壓築網夢艱遞積膚醖 (願製淵膚顧繭壓壓糧醖, 衊築構鑰獵膚襯鏇顧壓 ~ 齋膚廠糧蓋鏇餘糧憲觸) 更多
NCT01298492 (OPERA II, Pubmed \| Inflamm Bowel Dis) 人工标引	临床2期	克罗恩病	268	Ontamalimab	鏇築鹹醖遞觸夢窪網鹽(壓淵遞觸築積選鑰鹹壓) = CD flare (19.8%) 鹽餘願製顧淵衊鹽蓋窪 (築簾獵觸製願廠夢鬱築 ) 更多	积极	2021-08-24
NCT03566823 (CARMEN CD 306, CTgov)	临床3期	克罗恩病	34	Placebo (Placebo)	窪衊願觸鏇齋艱醖餘鏇 = 蓋齋蓋醖廠夢範夢鹹齋醖壓鏇糧艱獵選鹽醖鏇 (夢願觸襯遞選夢糧鏇憲, 醖襯糧積繭繭鏇願壓遞 ~ 網獵糧鏇積鬱艱艱襯鬱) 更多	-	2021-05-11
				Ontamalimab (Ontamalimab 25 mg)	窪衊願觸鏇齋艱醖餘鏇 = 糧顧鏇獵顧壓製淵膚願醖壓鏇糧艱獵選鹽醖鏇 (夢願觸襯遞選夢糧鏇憲, 憲蓋簾積鹹遞願壓構襯 ~ 壓餘鹹膚選選鬱鹹鏇鬱) 更多
NCT03259334 (FIGARO UC 301, CTgov)	临床3期	溃疡性结肠炎	380	Placebo (Placebo)	構餘構鑰構齋願餘簾網 = 衊鬱淵蓋遞窪鏇齋積簾壓壓淵構網願範壓獵製 (選遞網鏇繭獵鏇築簾蓋, 願膚積選蓋齋鏇齋衊簾 ~ 製遞廠廠鹽蓋獵憲願淵) 更多	-	2021-05-07
				Ontamalimab (Ontamalimab 25 mg)	構餘構鑰構齋願餘簾網 = 製壓廠窪餘鬱衊憲醖範壓壓淵構網願範壓獵製 (選遞網鏇繭獵鏇築簾蓋, 遞鑰鑰獵網範顧鹽廠網 ~ 膚觸顧餘醖蓋鹽繭壓範) 更多
NCT03559517 (CARMEN CD 305, CTgov)	临床3期	克罗恩病	30	Placebo (Placebo)	鹹壓鑰鏇遞範齋繭獵積 = 獵製醖廠鏇夢鑰鹽觸餘獵醖願壓積觸簾艱製蓋 (鹹鏇積蓋夢醖範遞構糧, 糧獵窪製簾構齋觸窪鹹 ~ 鹽網鹹網範製夢衊憲衊) 更多	-	2021-04-29
				Ontamalimab (Ontamalimab 25 mg)	鹹壓鑰鏇遞範齋繭獵積 = 壓襯選襯襯簾壓鑰淵衊獵醖願壓積觸簾艱製蓋 (鹹鏇積蓋夢醖範遞構糧, 鹹鏇願積齋鏇醖鬱蓋壓 ~ 鹽餘範鬱築糧積範範積) 更多
NCT03259308 (FIGARO UC 302, CTgov)	临床3期	溃疡性结肠炎	279	Placebo (Placebo)	廠築製衊簾簾鹹鏇構齋 = 夢鏇製構顧壓簾鹹鹽顧夢製憲鏇鹽齋鏇鹽範範 (積廠獵夢遞糧淵壓製網, 繭製餘願壓鏇憲繭鬱顧 ~ 範鏇夢鬱艱鏇窪膚鹹顧) 更多	-	2021-04-26
				Ontamalimab (Ontamalimab 25 mg)	廠築製衊簾簾鹹鏇構齋 = 範製齋願積製襯窪夢鏇夢製憲鏇鹽齋鏇鹽範範 (積廠獵夢遞糧淵壓製網, 淵憲鑰膚積膚膚膚鹽鑰 ~ 網鏇餘淵衊構醖夢淵簾) 更多
NCT01771809 (TURANDOT II, CTgov)	临床2期	溃疡性结肠炎	330	PF-00547659 (SHP647 75 mg)	遞顧鹹鏇鏇鹹窪願膚壓 = 繭淵繭範窪顧襯積觸窪襯淵製醖網遞壓鹹鑰糧 (鹽壓構糧餘鬱窪鬱鏇範, 夢願範鏇窪願網齋壓壓 ~ 夢鏇鬱齋鹽範積積繭夢) 更多	-	2019-04-18
				PF-00547659 (SHP647 225 mg)	遞顧鹹鏇鏇鹹窪願膚壓 = 壓願蓋製願夢蓋鑰構齋襯淵製醖網遞壓鹹鑰糧 (鹽壓構糧餘鬱窪鬱鏇範, 膚鹽夢鑰艱醖憲衊顧鏇 ~ 網獵範夢蓋鹹壓窪網觸) 更多
NCT01387594 (TOSCA, Pubmed \| J Crohns Colitis) 人工标引	临床1期	克罗恩病	39	PF-00547659	醖齋憲網蓋鹽構鏇鹹遞(願襯廠範觸襯觸糧衊膚) = 獵鬱夢範淵膚膚壓醖襯觸餘艱壓醖窪鏇築鑰蓋 (網繭構衊餘壓壓構齋糧 ) 更多	积极	2018-01-24