This multicenter, prospective, observational, non-interventional study investigates patients with intracranial hemorrhage under effective anticoagulation with dabigatran or vitamin-K antagonist (VKA). Routine data will be collected during hospitalization. Patients aged 18 years or older under effective therapy with dabigatran and symptomatic intracranial bleeding confirmed by cerebral imaging and treated with idarucizumab will be compared to patients under effective treatment with VKA at the time of onset of the intracranial bleeding. Ninety-five dabigatran patients who provided written informed consent for data transmission will be included. As control group retrospective and anonymized data of 285 VKA patients patients under VKA treatment and admitted to RIC-ICH study centers will be used. For each patient receiving idarucizumab, three patients with intracranial hemorrhage under effective treatment with VKA, will be included (retrospective) in the study. In addition, data of VKA patients will be transferred from the RASUNOA-PRIME and the "Erlanger Hirnblutungs-Register".

开始日期2019-09-19

申办/合作机构

University Hospital Of Essen

NCT02798107

/ WithdrawnN/A

Safety of Potential Paediatric Patients Treated With Idarucizumab: a Non-internventional Chart Review Study

Idarucizumab is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran with very high affinity. Idarucizumab potently and specifically binds to dabigatran and its metabolites and neutralises its anticoagulant effect. A clinical development program is ongoing to support marketing authorisation submissions for idarucizumab indicated in patients treated with dabigatran who require emergency surgery/urgent procedures or who have a life-threatening or uncontrolledbleeding when rapid reversal of the anticoagulant effects of dabigatran is required.

开始日期2019-05-20

申办/合作机构

Boehringer Ingelheim GmbH

NCT03359889

/ CompletedN/A

Post Marketing Surveillance Program of Praxbind Use in India.

This program will be initiated after the commercial availability of PraxbindTM in India. It will include patients administered with PraxbindTM into the surveillance program after commercial availability in 2 years at selected centres approved by the regulatory authority.

开始日期2018-12-26

申办/合作机构

Boehringer Ingelheim GmbH

100 项与依达赛珠单抗相关的临床结果

登录后查看更多信息

100 项与依达赛珠单抗相关的转化医学

登录后查看更多信息

100 项与依达赛珠单抗相关的专利（医药）

登录后查看更多信息

567

项与依达赛珠单抗相关的文献（医药）

2025-12-01·JOURNAL OF EMERGENCY MEDICINE

Latin America Multidisciplinary Consensus Panel on Management of Severe Bleeding in the Anticoagulated Patient

Article

作者: Noble-Lugo, Alejandra ; Meillon-Garcia, Luis Antonio ; Colunga-Lozano, Luis Enrique ; Guerra, Joao Carlos de Campos ; Ceresetto, Jose Manuel ; Rosales, Julieta S ; Pontes-Neto, Octávio M ; Arenas, Ana Cristina Montenegro ; Kreitzer, Natalie P ; Gibler, W Brian ; Tellez, Luis Eduardo Vargas ; Rodrigues, Roseny Dos Reis

BACKGROUND:

Bleeding is the most important complication associated with anticoagulants. Patients experiencing bleeding while on an anticoagulation require proper risk stratification, which involves careful assessment of multiple factors, including hemodynamic stability, the origin of bleeding, and the extent of blood loss. Over the last several decades, important advances have been made in the field of anticoagulant therapy and reversal.

OBJECTIVES:

This manuscript provides a review of anticoagulant related hemorrhages, with particular emphasis on topics most relevant to Latin America. It offers an updated assessment of evidence-based strategies for managing major bleeding related to anticoagulation. We will also explore what happens to patients in real-life situations, where there are not specific reversal agents available.

DISCUSSION:

While minor bleeding can usually be managed simply by discontinuing the anticoagulant, major bleeding is a medical emergency that may threaten life and require the administration of blood products and the utilization of specific antidotes. Fresh frozen plasma (FFP) or prothrombin complex concentrates (PCCs) can be administrated for major bleeding incidents linked to warfarin. Protamine sulfate is administrated for unfractionated heparin and partially for low-molecular-weight heparin (LMWH). Idarucizumab is the reversal agent for dabigatran, while andexanet alfa is approved for the reversal of oral factor Xa inhibitors.

CONCLUSIONS:

This review highlights the significance of appropriate risk stratification and management strategies for bleeding complications associated with anticoagulants. The manuscript emphasizes the need for adaptable management strategies in regions like Latin America, where resource limitations may impact the availability of specific reversal agents.

2025-10-01·ANESTHESIOLOGY

Intravenous Dabigatran for Anticoagulation during Cardiopulmonary Bypass in a Sheep Model

Article

作者: Stefanos, Tatsiana ; Nadtochiy, Sergiy M. ; Angona, Ronald E. ; Swartz, Michael F. ; Gu, Yang ; LeMoine, Dana ; Major, Lauren A. ; Jones, Karen ; Anderson, Brian J. ; Feng, Changyong ; Darrow, Nathan ; Eaton, Michael P.

Background::

Heparin is the standard anticoagulant used during cardiopulmonary bypass (CPB). However, there are problems with heparin, including immunogenicity and variability of effect, that make a search for an alternative desirable. Dabigatran anticoagulation has been reported to provide adequate conditions for CPB in a rabbit model. This study used a sheep model of CPB to assess the efficacy of dabigatran and its reversibility with idarucizumab.

Methods::

Twelve sheep were subjected to 120 min of CPB after anticoagulation with either intravenous dabigatran or heparin (N = 6 per group). In both groups, activated clotting time, kaolin/tissue factor–activated thromboelastography reaction time, and blood gases were monitored during and after CPB. Plasma dabigatran concentrations were measured during and after CPB. After CPB, two sections of each arterial filter were examined for thrombus using electron microscopy. Idarucizumab or protamine was administered after CPB to reverse anticoagulation, and the sheep were monitored for a subsequent 24 h. Plasma concentrations of inflammatory and coagulation markers were assessed at baseline, after 120 min of CPB, and 6 h after reversal administration.

Results::

After 120 min of CPB, there was no visible thrombus or fibrin observed on the arterial line filters in either the dabigatran or heparin groups. Plasma dabigatran concentrations during CPB were below the target concentration (5 µg/ml), ranging from 1.7 ± 0.4 to 3.4 ± 1.5 µg/ml. In both groups, reaction time and activated clotting time values increased during CPB and then returned to nearly baseline levels after administration of the reversal agents. Interleukin-6 concentrations were elevated in the heparin group compared to the dabigatran group. Five sheep survived 24 h after idarucizumab administration. Four of six sheep survived 24 h after the administration of protamine.

Conclusions::

This study demonstrates that dabigatran effectively provides anticoagulation in a sheep CPB model, and idarucizumab successfully reverses its effects.

2025-10-01·STROKE

Intravenous Thrombolysis in Patients With Recent Intake of Direct Oral Anticoagulants: A Target Trial Analysis and Comparison With Reversal Agent Use

Article

作者: Boulanger, Marion ; Allardt, Arne ; Stufano, Gianluca ; Longoni, Marco ; Barber, P. Alan ; Hahn, Marianne ; Yakushiji, Yusuke ; Vlachos, Dimitrios ; D’Anna, Lucio ; Lemmens, Robin ; Maes, Louise ; Valente, Mariarosaria ; Giannakakis, Michail ; Ceccarelli, Laura ; Riegler, Christoph ; Rauch, Janis ; Tyson, Alicia ; Siepen, Bernhard ; Piechowiak, Eike ; Touzé, Emmanuel ; Gomez-Exposito, Alexandra ; Davis, Alan J. ; Kurmann, Christoph ; Auer, Elias ; Scoppettuolo, Pasquale ; Cordici, Francesco ; Peeters, André ; Scutelnic, Adrian ; Kunieda, Takenobu ; Dittrich, Tolga ; Paiva Nunes, Ana ; Dobrocky, Tomas ; Mujanovic, Adnan ; Meinel, Thomas R. ; Marto, João Pedro ; Andreone, Vincenzo ; Candelaresi, Paolo ; Aguiar de Sousa, Diana ; Bücke, Philipp ; Seiffge, David J. ; Ghannam, Malik ; Woock, Malin ; Spina, Emanuele ; Valletta, Francesco ; Pfeilschifter, Waltraud ; Thevoz, Guillaume ; De Marchis, Gian Marco ; Kraemer, Christoffer ; Kleeberg, Antonia ; Beyeler, Morin ; Zedde, Marialuisa ; Clenin, Leander ; Frol, Senta ; Guerreiro, Carolina ; Pretnar Oblak, Janja ; Kaesmacher, Johannes ; Alshaer, Qasem N. ; Demeestere, Jelle ; Merlino, Giovanni ; Ntaios, George ; Rodrigues, Bárbara ; Fischer, Urs ; Goeldlin, Martina ; Herrmann, Matthias ; Sökeland, Greta ; Mannino, Marina ; Mariano, Marisa E. ; Alsawareah, Ashraf ; Heldner, Mirjam ; Tudisco, Valentina ; Romoli, Michele ; Papadimitriou, Dimitra ; Uphaus, Timo ; Burini, Alessandra ; Wu, Teddy Y. ; Strambo, Davide ; Ranta, Anna ; Muppa, Jayachandra ; Kristoffersen, Espen Saxhaug ; Padjen, Visnja ; Olalde, Heena ; Henninger, Nils ; Kermer, Pawel ; Michel, Patrik ; Zipser-Mohammadzada, Freschta ; Poli, Sven ; Tentolouris, Vasilis ; Nolte, Christian H. ; Purrucker, Jan C.

BACKGROUND::

Intravenous thrombolysis (IVT) in patients with recent ingestion of direct oral anticoagulants (DOACs) is a frequent challenge and remains controversial. The benefit of DOAC reversal before IVT is uncertain.

METHODS::

Using target trial methodology, we analyzed data from 28 comprehensive stroke centers. Patients on DOACs were included if they met IVT criteria, had a National Institutes of Health Stroke Scale score of ≥2, and last DOAC intake within 48 hours or was undeterminable. Safety and efficacy outcomes (symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, major bleeding, 90-day mortality, and good functional outcome [modified Rankin Scale score of 0–2 or return to baseline]) were compared between those receiving IVT versus no IVT and IVT with versus without reversal. In addition, a comparison was made with patients from the New Zealand stroke registry, all of whom underwent reversal with idarucizumab. We adjusted for covariates known to be associated with safety and efficacy outcomes, including age, stroke severity, intended thrombectomy, blood glucose, blood pressure, DOAC reversal, and time from last intake.

RESULTS::

Overall, 1342 patients fulfilled the target trial criteria. The median age was 80 (interquartile range, 73–86) years, median National Institutes of Health Stroke Scale score was 11, 50% were female, and 52% of patients received endovascular therapy. IVT was given in 342 of 1342 (25%) patients. Of these, 141 (41.2%) had verified DOAC intake <12 hours before admission, and 92 (26.9%) within 12 to 24 hours. Symptomatic intracerebral hemorrhage occurred in 10 of 328 (3.0%) of patients receiving IVT and 54 of 921 (5.9%) patients not receiving IVT (adjusted difference, −2.1% [95% CI, −5.3% to +1.2]). Patients receiving IVT were more likely to have good functional outcomes (adjusted difference, +14.4% [95% CI, +7.1% to +21.8%]). Comparing 289 patients with reversal (from the additional New Zealand registry) and 283 patients without reversal before IVT (from the target trial population), there was no significant difference in symptomatic intracerebral hemorrhage, major bleeding, or efficacy outcomes.

CONCLUSIONS::

This target trial confirms previous observational data regarding the safety of off-label IVT in patients with recent DOAC intake. More data and dedicated trials are needed for patients with confirmed high DOAC plasma levels and regarding the efficacy and safety of DOAC reversal before IVT.

项与依达赛珠单抗相关的新闻（医药）

2025-11-12

·科普动画冲冲冲

抗凝剂: 直接因子抑制剂

药理学深度解析：直接因子抑制剂抗凝药物一、凝血机制与抗凝靶点凝血级联反应的精妙平衡人体凝血系统是一个精密的多层次"瀑布式"反应体系，直接因子抑制剂针对这一体系的关键环节进行精准干预。凝血途径详解关键节点作用机制凝血酶的核心地位• 多功能酶：催化纤维蛋白原转化为纤维蛋白• 正反馈调节：激活因子V、VIII、XI、XIII• 血小板激活：促进血小板聚集和释放反应抗凝治疗靶点选择理想靶点特征• 关键节点：在凝血途径中处于核心位置• 特异性强：减少非目标效应• 治疗窗宽：安全性较好二、直接凝血酶抑制剂药物分类与特性不同药物比较具体药物特性达比加群酯• 前体药物：口服后在体内转化为活性形式• 作用直接：无需抗凝血酶III参与• 双相消除：肾脏消除80%，其余经肝脏比伐卢定• 短效制剂：半衰期25分钟，需持续输注• 可逆结合：与凝血酶可逆性结合• HIT适用：肝素诱导血小板减少症的首选药理作用特点独特作用机制• 结合位点：直接作用于凝血酶的活性位点• 靶点覆盖：抑制游离型和纤维蛋白结合型凝血酶• 无共因子依赖：不依赖抗凝血酶III发挥作用与传统肝素对比优势参数普通肝素直接凝血酶抑制剂作用靶点多个凝血因子特异性抑制凝血酶抗凝监测需要监测aPTT 通常无需监测 HIT风险较高几乎无风险鱼精蛋白可逆转无特异性拮抗剂三、直接Xa因子抑制剂药物家族特征代表药物比较药代动力学参数药物半衰期肾脏排泄起效时间用法利伐沙班 5-9小时 33% 2-4小时一日一次阿哌沙班 8-15小时 27% 3-4小时一日两次依度沙班 8-10小时 50% 1-3小时一日一次作用机制优势级联放大效应临床优势体现• 治疗窗宽：固定剂量给药，无需常规监测• 相互作用少：与食物相互作用小• 起效快速：口服后2-4小时达峰浓度四、实验室监测与评估凝血功能检测不同检测方法的敏感性检测指标直接凝血酶抑制剂直接Xa因子抑制剂临床意义 PT/INR 轻度延长明显延长筛查有用 aPTT 中度延长轻度延长敏感性一般 TT 显著延长无影响特异性高抗Xa活性无影响直接相关定量监测特殊情况下的监测需求治疗药物监测指征• 极端体重：BMI<18或>40 kg/m²• 肾功能不全：eGFR<30 mL/min/1.73m²• 老年人：年龄>75岁，多重用药• 出血或血栓事件：评估药物暴露量五、临床应用指南适应证与剂量策略静脉血栓栓塞防治急性期治疗• 利伐沙班：前3周15mg bid，后续20mg qd• 阿哌沙班：前7天10mg bid，后续5mg bid• 依度沙班：60mg qd（肌酐清除率>50mL/min）房颤卒中预防剂量调整因素特殊人群用药肾功能不全患者• 轻度损伤（CrCl 50-80mL/min）：常规剂量• 中度损伤（CrCl 30-50mL/min）：剂量减量• 重度损伤（CrCl 15-30mL/min）：谨慎使用• 终末期肾病（CrCl<15mL/min）：一般避免使用老年患者考量• 生理变化：肾功能减退，分布容积改变• 出血风险：年龄每增加10岁，风险增加1.5倍• 跌倒风险：评估跌倒倾向，权衡获益风险六、不良反应管理出血并发症处理出血风险评估工具 HAS-BLED评分系统• H：高血压（1分）• A：肝肾功能异常（各1分）• S：卒中史（1分）• B：出血史（1分）• L：INR不稳定（1分）• E：老年人（1分）• D：药物或饮酒（各1分）出血处理策略轻微出血• 局部处理：压迫止血• 暂时停药：暂停1-2次剂量• 监测观察：症状和血红蛋白变化严重出血特异性逆转剂应用药物逆转剂作用机制使用方法达比加群依达赛珠单抗特异性抗体结合 5g静脉输注 Xa抑制剂安达昔单抗诱饵受体竞争根据出血严重程度调整剂量非特异性止血措施• 凝血酶原复合物：含因子II、VII、IX、X• 活化凝血因子VIIa：促进血栓形成• 氨甲环酸：抗纤溶治疗七、药物相互作用代谢途径相关的相互作用 CYP450酶系影响重要相互作用组合抑制剂药物受影响DOAC 风险等级管理建议酮康唑所有Xa抑制剂高危避免联用利托那韦利伐沙班高危禁忌地尔硫卓阿哌沙班中危监测调整胺碘酮所有DOAC 中危谨慎使用转运蛋白影响 P-糖蛋白相互作用• 强抑制剂：维拉帕米、奎尼丁、环孢素• 强诱导剂：利福平、卡马西平、苯妥英• 临床意义：影响药物吸收和分布八、特殊情境应用围手术期管理停药时间指南基于肾功能决策出血风险 CrCl≥80mL/min CrCl 50-80mL/min CrCl 30-50mL/min 低风险手术停药24小时停药36小时停药48小时高风险手术停药48小时停药72小时停药96小时逆转治疗指征急诊手术或严重出血• 紧急程度：根据出血严重性和手术紧迫性• 实验室评估：凝血功能检测和药物浓度• 多学科协作：血液科、药学、重症医学共同决策九、疗效与安全性证据大型临床试验总结房颤卒中预防研究研究名称药物样本量主要结果 RE-LY 达比加群 18,113 卒中预防优于华法林 ROCKET-AF 利伐沙班 14,264 不劣于华法林 ARISTOTLE 阿哌沙班 18,201 优于华法林，出血少 ENGAGE-AF 依度沙班 21,105 不劣于华法林，出血少静脉血栓治疗证据急性期与长期治疗• EINSTEIN研究：利伐沙班单药治疗VTE• AMPLIFY研究：阿哌沙班与标准治疗比较• HOKUSAI-VTE：依度沙班个体化疗程十、未来发展方向新型抗凝药物研发作用靶点创新因子XI抑制剂• 理论优势：预防血栓同时减少出血风险• 作用机制：抑制内源性途径，保持止血功能• 研发阶段：多项III期临床试验进行中给药方式改进长效制剂开发• 每周一次：提高依从性• 皮下给药：适合不能口服患者• 个体化剂量：基于基因型或生物标志物精准抗凝治疗药物基因组学应用• 代谢酶多态性：CYP450基因型指导剂量• 转运体变异：ABCBI基因影响生物利用度• 个体化治疗：基于药代动力学模型结语直接因子抑制剂代表了抗凝治疗的重大进步，为血栓性疾病的预防和治疗提供了更安全、便捷的选择。随着对这类药物认识的深入和新型药物的研发，抗凝治疗正朝着更加个体化、智能化的方向发展。

临床3期

2025-10-30

·药明康德DMPK

抗体片段药物介绍及其药代动力学特征

前言抗体疗法是一种利用基于抗体的分子治疗疾病的靶向治疗形式。单克隆抗体（mAbs）是由血浆B细胞在特定抗原的刺激下产生的免疫球蛋白。抗体在人体免疫系统中可以发挥多种作用，如促进体液和细胞对多种抗原的免疫反应，具有高特异性和长期疗效。自美国食品和药物管理局（FDA）于1986年批准首个单克隆抗体莫罗莫那-SD3以来，抗体已成为一类主要的治疗药物。目前全球已经有超过200种抗体疗法获得批准[1]，涵盖癌症、免疫相关疾病、传染病和血液病等疾病领域。抗体疗法的优势在于其高选择性和对靶点的高亲和力。在过去的四十年里，抗体类药物的开发模式经历了快速发展和迭代，从传统的单克隆抗体扩展到抗体偶联药物（ADC）、双/多特异性抗体以及抗体片段等不同的药物形式[2]。本文主要介绍抗体片段药物进展情况及其药代动力学特征。图1. 抗体模式:典型抗体（a）、抗体-药物偶联物（b）、双特异性抗体（c）和抗体片段（d）。片段包括抗原结合片段（Fabs）、单链可变区（scFv）构建体和结构域抗体。[2] 抗体片段药物的介绍抗体分子可以通过生化或遗传手段提取单独的结构域。这些单独的结构域衍生的抗体片段药物可以分为三类：抗原结合片段（Fab）、单链可变片段（scFv）和重链可变片段（VHH, nanobody），已上市抗体片段药物见表1[1,3]。以下分别介绍各类抗体片段。 ➤ 抗原结合片段（Fab）用木瓜蛋白酶切割铰链区上方的重链，抗体可被分解为Fc片段（可结晶片段）和两个Fab片段。Fab片段的分子量约为50 kDa，仅为完整抗体的1/3，具有更好的组织渗透性。此外，由于缺少Fc区，Fab片段不会引起抗体依赖的细胞介导的细胞毒作用（ADCC）、抗体依赖性细胞介导的吞噬作用（ADCP）、补体依赖的细胞毒性作用（CDC）等功能效应，体内的半衰期也明显缩短。Fab是最早的单克隆抗体（mAb）片段治疗药物，至今FDA已批准4个上市药物，包括阿昔单抗（abciximab）、雷珠单抗（ranibizumab）、培塞利珠单抗（certolizumab pegol）和依达赛珠单抗（idarucizumab），如表1所示。表1. 已上市抗体片段药物 ➤ 单链可变片段（scFv）单链可变片段（scFvs）是一种重组分子，其中编码抗原结合域的轻、重免疫球蛋白链的可变区域被设计成单个多肽。一般来说，VH和VL序列通过一个灵活的连接子序列连接，并产生一系列变体，以优化结合亲和力和稳定性[4]。骨架多样化的scFv分子通过互补区域结合形成二价分子，互补的scFv本身以单链的形式存在（串联scFv），以及双特异性串联scFv（bis-scFvs）等[4]。FDA已批准4个单链可变片段（scFvs）类上市药物。贝林妥欧单抗（blinatumomab）是一种靶向CD19/CD3双特异性串联scFv，于2014年被批准用于治疗急性淋巴细胞白血病。帕西妥莫单抗（moxetumomab pasudotox）是一种可识别人CD22的抗体-药物偶联物，于2018年被批准用于治疗毛细胞白血病。布西珠单抗（brolucizumab）是一种靶向抑制VEGF-A的人源化scFv，于2019年被批准用于治疗新生血管性年龄相关性黄斑变性。特本塔夫斯普（tebentafusp）是一种新型T细胞受体（TCR）双特异性免疫疗法，由可溶性TCR与抗CD3免疫效应器结构域融合而成，于2022年被批准用于治疗转移性葡萄膜黑色素瘤。 ➤ 重链可变片段（VHH, nanobody）骆驼体内存在天然的缺失轻链的重链抗体，克隆其可变区可以获得只有重链可变区组成的单域抗体，称为VHH（variable domain of heavy chain antibody），也称为纳米抗体（Nb，nanobody，a single domain antibody），它是最小的功能性抗原结合片段[5]。 VHH与传统IgG抗体的VH有相同的结构域（图2），包含保守的框架区（FR1、FR2、FR3 和 FR4）以及互补决定区（CDR1、CDR2和CDR3）。VH在FR2区中存在四个高度保守的疏水氨基酸（V37、G44、L45和W47）。而VHH将这些残基替换为亲水氨基酸（F37、E45、R47和G52），从而增强了溶解性。此外，VHH的CDR1与CDR3通过环间二硫键连接，从而提高了结构稳定性。另外，VHH的CDR1和CDR3的平均长度比VH的对应的CDR略长。VHH灵活的CDR3环犹如细长的“手指”，可以进入传统抗体无法到达的靶抗原空腔，从而实现更好的功能活性[5]。图2. (A)传统IgG抗体具有两条相同的重链，由VH、CH1、CH2和CH3结构域组成，以及两条相同的轻链，由VL和CL结构域组成。骆驼重链抗体含有一个VHH和两个恒定区域（CH2和CH3）。(B)VH和VHH的氨基酸序列的差异，以及VH和VHH的折叠结构。[5] VHH具有高效组织渗透、高稳定性、耐极端条件、高溶解度等优点。VHH在4°C和-20°C下的保质期长、耐受高温（60-80°C）和蛋白水解、耐受非生理pH（3.0-9.0）、耐受高压（500-750 MPa）。与传统抗体（分子量约150 kDa）相比，作为最小的抗体片段，VHH（分子量约15 kDa）组织穿透性最好，可以到达传统抗体达不到的病灶组织。另外，纳米抗体能够有效的穿透血脑屏障，为脑部给药提供了新方法。但由于分子量较小，纳米抗体容易被肾脏快速清除，半衰期较短，这既避免了潜在毒性作用，也限制了其持续疗效，可以通过聚乙二醇化、与白蛋白结合或融合、与抗体的Fc融合等手段延长半衰期。另外，VHH与人类的VH序列相似性很高（约75-90%），因此免疫原性较低。截止目前，全球已获批上市3款VHH药物，包括2018年FDA批准上市的二价的VHH药物卡普拉珠单抗（caplacizumab）、2021年在中国获批上市的VHH-Fc融合蛋白药物恩沃利单抗、2022年在日本获批上市的三价的VHH药物ozoralizumab，如表1所示。抗体片段药物和单克隆抗体的比较与单克隆抗体相比，抗体片段药物的优势和劣势较为明显，表2总结了各类抗体片段药物与单克隆抗体的优劣势对比[6]。抗体片段药物由于没有Fc段，体内半衰期相较于完整抗体明显缩短，但同时组织渗透能力增强。同时，抗体片段在水溶性、稳定性等方面表现出优势。表2. 抗体片段药物与单克隆抗体药物的优劣势对比[6] 抗体片段药物的DMPK策略与抗体药物相似，抗体片段药物在申报过程中所需提交的DMPK材料主要包括药物代谢动力学（PK）相关的体内数据。在进行抗体片段药物的PK试验设计时，需要考虑以下因素： ● 药物本身的性质； ● 药物的适应症。已上市抗体片段药物在申报中提交的非临床药代动力学研究介绍如表3所示。雷珠单抗和布西珠单抗均靶向VEGF-A，用于治疗眼部疾病。在向FDA提交的资料中，二者均提供了猴和兔的玻璃体内（IVT）给药相关的药动学数据。IVT给药后，应采集玻璃体、房水、视网膜各层及其他眼部组织（如睫状体、虹膜、角膜内皮）以及血清，以监测药物浓度和抗药物抗体（ADA）效应。特本塔夫斯普是一种新型双特异性蛋白，由可溶性TCR与抗CD3免疫效应器结构域融合而成：一端是具有高亲和力的可结合特定抗原的可溶性T细胞受体，另一端是识别CD3的免疫效应结构域。它靶向gp100，因其识别的是人HLA呈递的gp100肽，缺乏合适的常规模拟动物模型，故研究者只在小鼠中进行了药代动力学评估。相较于抗体药物，抗体片段药物的分子量较低，具有更佳的组织渗透性，因此在某些情况下也需考察抗体片段药物的组织分布情况。培塞利珠单抗是通过将50 kDa的人源化IgG Fab片段与40 kDa的聚乙二醇（PEG）组分结合而制成的。卡普拉珠单抗由259个氨基酸组成，通过AAA连接子（由三个丙氨酸构成）连接两个128个氨基酸的抗vWF（冯·维勒布兰德因子）的人源化纳米抗体，分子量不足28 kDa。在这两种药物向FDA提交的申请材料中，除常规的体内血清PK测试外，还进行了125I标记的放射性组织分布测试。另外，依达赛珠单抗和卡普拉珠单抗还开展了动物种属中的尿液排泄实验。对于抗体片段药物，常用的检测方法包括酶联免疫吸附测定（ELISA）、液相色谱-质谱联用（LC-MS/MS）以及Western-Blot等。药明康德DMPK能够提供多种检测方法，包括ELISA、MSD电化学发光技术、Hybrid LBA-LC-MS以及专门用于测定缺乏保守区域的抗体片段药物的通用敏感竞争性酶联免疫吸附测定（USCE）等。表3. 已上市抗体片段药物的非临床药代动力学研究概览[3] 结语与展望抗体片段药物相比完整抗体，由于其良好的组织渗透性、低免疫原性等优势，在治疗和诊断领域有巨大的应用潜力。VHH表现出相对突出的稳定性、高的溶解度以及较好的组织渗透性等优势，由VHH构成的双特异性抗体成为当前研究的热点之一。Sorriso Pharmaceuticals开发的SOR102是一种能够同时靶向TNF-α和IL-23p19的口服VHH双特异性抗体；Genentech亦报道了相关的口服VHH药物[7]。此外，洛启生物开发的VHH吸入给药药物LQ036和LQ043H正在开展临床试验。辐联医药基于VHH开发的放射性偶联药物FL801，表现出较好的抗肿瘤活性和较低的肾脏蓄积。总结如表4所示。近年来，抗体片段药物基于自身优势，在药物研发领域展现出巨大潜力。它们不仅能够实现如口服、吸入等多样化的给药途径，还可扩展传统抗体难以覆盖的疾病领域，推动抗体药物向更广泛、更精准的临床应用发展，成为抗体药物创新的重要驱动力。表4. 抗体片段药物最新进展案例参考文献： [1] https://www.antibodysociety.org/resources. [2] Mullard A. FDA approves 100th monoclonal antibody product. Nat Rev Drug Discov. 2021;20(7):491-495. doi:10.1038/d41573-021-00079-7 [3] https://www.fda.gov [4] Nelson AL. Antibody fragments: hope and hype. MAbs. 2010;2(1):77-83. doi:10.4161/mabs.2.1.10786 [5] Muyldermans S, Baral TN, Retamozzo VC, De Baetselier P, De Genst E, Kinne J, Leonhardt H, Magez S, Nguyen VK, Revets H, Rothbauer U, Stijlemans B, Tillib S, Wernery U, Wyns L, Hassanzadeh-Ghassabeh G, Saerens D. Camelid immunoglobulins and nanobody technology. Vet Immunol Immunopathol. 2009 Mar 15;128(1-3):178-83. [6] Liu L, Tu B, Sun Y, Liao L, Lu X, Liu E, Huang Y. Nanobody-based drug delivery systems for cancer therapy. J Control Release. 2025 May 10;381:113562. [7] Ota N, Davies CW, Kang J, Yan D, Scherl A, Wong A, Cook R, Tao X, Dunlap D, Klabunde S, Mantik P, Mohanan V, Lin W, McBride J, Sadekar S, Storek KM, Lupardus P, Ye Z, Ackerly Wallweber H, Kiefer JR, Xu M, Chan P, Nagapudi K, Yi T, Koerber JT. Engineering a protease-stable, oral single-domain antibody to inhibit IL-23 signaling. Proc Natl Acad Sci U S A. 2025 Jun 3;122(22):e2501635122. （下滑查看更多）作者：卢雪怡，程起干，金晶编辑：钱卉娟，富罗娜·克里木设计：张莹莹推荐阅读药明康德DMPK 依托在中国（上海、苏州、南京和南通）和美国（新泽西）的研发中心，提供从早期筛选、临床前开发、到临床研究阶段的综合型药代动力学服务，助力您快速推进药物研发流程。拥有上千人的研发团队，服务超1600家全球客户，具有超过十五年的新药申报经验，已成功支持超过1700个新药临床研究申请（IND）。免责声明：药明康德DMPK团队专注于分享药物代谢与药代动力学相关领域进展和研究经验总结。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德DMPK团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德DMPK」微信公众号回复“转载”，获取转载须知。喜欢本文就点赞在看吧

上市批准抗体药物偶联物免疫疗法

2025-08-29

·EINPresswire

July - September 2021 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS)

Ajovy (fremanezumab-vfrm) Emgality (galcanezumab-gnlm) Nurtec ODT (rimegepant) Ubrelvy (ubrogepant) Vyepti (eptinezumab-jjmr) Hypertension The "Warnings and Precautions", "Adverse Reactions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in March 2025 to include information about the risk of hypertension. Example: Ajovy labeling Apriso (mesalamine) Asacol (mesalamine) Asacol HD (mesalamine) Azulfidine (sulfasalazine) Azulfidine EN-Tabs (sulfasalazine) Canasa (mesalamine) Colazal (balsalazide disodium) Delzicol (mesalamine) Dipentum (osalazine sodium) Giazo (balsalazide disodium) Lialda (mesalamine) Rowasa (mesalamine) Pentasa (mesalamine) Severe cutaneous adverse reactions The Warnings and Precautions section of the labeling was updated November 2021 to include severe cutaneous adverse reactions. Example: Delzicol labeling Avastin (bevacizumab) Mvasi (bevacizumab-awwb) Zirabev (bevacizumab-bvzr) Pancreatitis FDA determined that no action is necessary at the time based on available information. Avastin (bevacizumab) Mvasi (bevacizumab-awwb) Zirabev (bevacizumab-bvzr) Anaphylactic shock The "Warnings and Precautions" section of the labeling was updated between September 2022 and February 2023 to include anaphylactoid/anaphylactic reactions. Example: Avastin labeling Ayvakit (avapritinib) Photosensitivity reaction The "Warnings and Precautions", "Adverse Reactions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in March 2023 to include information about photosensitivity. Ayvakit labeling Azacitidine Onureg (azacitidine) Vidaza (azacitidine) Generic products containing azacitidine Pericarditis The "Adverse Reactions" section of the labeling was updated between September 2022 and June 2023 to include pericarditis. Example: Vidaza labeling FDA determined that no action is necessary at the time based on available information for Onureg. Bavencio (avelumab) Imfinzi (durvalumab) Libtayo (cemiplimab-rwlc) Keytruda (pembrolizumab) Opdivo (nivolumab) Tecentriq (atezolizumab) Yervoy (ipilimumab) Tumour lysis syndrome FDA determined that no action is necessary at the time based on available information. Cymbalta (duloxetine hydrochloride) Drizalma Sprinkle (duloxetine hydrochloride) Generic products containing duloxetine hydrochloride Anosmia, Hyposmia This issue is posted as two individual newly identified safety signal (NISS) entries in the January-March 2022 quarter, to reflect the focus on the potential signals of anosmia and hyposmia, separately. Darzalex (daratumumab) Darzalex Faspro (daratumumab and hyaluronidase-fihj) Blood stem cell transplant failure FDA determined that no action is necessary at the time based on available information. Dipeptidyl peptidase-4 (DPP-4) inhibitors Glyxambi (empagliflozin and linagliptin) Janumet (metformin hydrochloride and sitagliptin phosphate) Janumet XR (metformin hydrochloride and sitagliptin phosphate) Jentadueto (linagliptin and metformin hydrochloride) Jentadueto XR (linagliptin and metformin hydrochloride) Kazano (alogliptin and metformin hydrochloride) Kombiglyze XR (metformin hydrochloride and saxagliptin) Nesina (alogliptin) Onglyza (saxagliptin) Oseni (alogliptin and pioglitazone) Steglujan (ertugliflozin and sitagliptin) Tradjenta (linagliptin) Trijardy XR (empagliflozin, linagliptin and metformin hydrochloride) Qtern (saxagliptin and dapagliflozin) Generic products containing dipeptidyl peptidase-4 inhibitors Tubulointerstitial nephritis The "Adverse Reactions" section of the labeling was updated between March 2022 and June 2022 for products containing alogliptin and sitagliptin to include tubulointerstitial nephritis. Example: Janumet labeling FDA determined that no action is necessary for products containing linagliptin and saxagliptin at the time based on available information. *An administrative error resulted in the omission of Januvia from the list of product names after the initial quarterly report was posted. Dupixent (dupilumab) Angioedema The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in December 2021 to include angioedema. Dupixent labeling Glucagon-like peptide-1 (GLP-1) analogues Adlyxin (lixisenatide) Bydureon (exenatide) Bydureon BCise (exenatide) Byetta (exenatide) Ozempic (semaglutide) Rybelsus (semaglutide) Saxenda (liraglutide) Soliqua 100/33 (insulin glargine and lixisenatide injection) Trulicity (dulaglutide) Victoza (liraglutide) Wegovy (semaglutide) Xultophy 100/3.6 (insulin degludec and liraglutide injection) Generic products containing glucagon-like peptide-1 analogues Gallbladder related disorders The "Warnings and Precautions", "Adverse Reactions", and "Patient Counseling Information" sections of the GLP-1 analogues labeling were updated between March 2022 and June 2022 to include information about acute gallbladder disease. Example: Adlyxin labeling FDA has determined that the last approved labeling for Saxenda and Wegovy is adequately labeled for acute gallbladder disease, and that no further regulatory action is needed at this time. Gonadotropin releasing hormone (GnRH) analogues Fensolvi (leuprolide acetate) Lupron Depot-PED (leuprolide acetate) Supprelin LA (histrelin acetate) Synarel (nafarelin acetate) Triptodur (triptorelin) Idiopathic intracranial hypertension The "Warnings", "Precautions", and "Adverse Reactions" sections of the labeling were updated in April 2022 to include idiopathic intracranial hypertension. Example: Fensolvi labeling Jakafi (ruxolitinib phosphate) Herpes simplex virus (HSV) reactivation and/or disseminated HSV The "Dosage and Administration", "Warnings and Precautions", and "Adverse Reactions" sections of the labeling were updated in January 2023 to include information about herpes simplex and herpes zoster infections. Jakafi labeling Ibrance (palbociclib) Kisqali (ribociclib) Kisqali Femara Co-Pack (letrozole and ribociclib) Embolic and thrombotic events, venous The "Adverse Reactions" section of the Ibrance labeling was updated in December 2024 to include venous thromboembolism. Ibrance labeling FDA determined that no action is necessary at the time for Kisqali and Kisqali Femara Co-Pack based on available information. Ocrevus (ocrelizumab) Myocardial infarction FDA determined that no action is necessary at the time based on available information. Potassium Chloride Product preparation error The “Warnings” section of the labeling was updated in December 2022 to include information about fatal cardiac adverse reactions with intravenous administration of undiluted potassium chloride. Praxbind (idarucizumab) Wrong dose errors The carton labeling and "Dosage and Administration" sections of the labeling were revised in February 2022 to clarify the number of vials included in each carton and the recommended dosing. Praxbind labeling Qbrexza (glycopyrronium tosylate) Accidental exposure to product The container label, carton labeling, "Dosage and Administration", "Warnings and Precautions", "Patient Counseling Information", and "Patient Information" sections of the labeling were updated in October 2022 to include information about accidental exposure. Qbrexza labeling Qbrexza (glycopyrronium tosylate) Urinary retention The “Warnings and Precautions”, “Adverse Reactions”, and “Patient Counseling Information” sections of the labeling were updated in October 2022 to include information about new or worsening urinary retention. Qbrexza labeling Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Farxiga (dapagliflozin) Glyxambi (empagliflozin and linagliptin) Invokamet (canagliflozin and metformin hydrochloride) Invokamet XR (canagliflozin and metformin hydrochloride) Invokana (canagliflozin) Jardiance (empagliflozin) Qtern (saxagliptin and dapagliflozin) Steglatro (ertugliflozin) Steglujan (ertugliflozin and sitagliptin) Segluromet (ertugliflozin and metformin hydrochloride) Synjardy (empagliflozin and metformin hydrochloride) Synjardy XR (empagliflozin and metformin hydrochloride) Trijardy XR (empagliflozin, linagliptin and metformin hydrochloride) Xigduo XR (dapagliflozin and metformin) Generic products containing sodium-glucose cotransporter-2 (SGLT-2) inhibitors Tubulointerstitial nephritis FDA determined that no action is necessary at the time based on available information. Somatostatin Receptor Imaging Agents Detectnet (copper Cu-64 dotatate injection) Gallium Dotatoc (GA 68) Octreoscan (Indium In 111 Pentetreotide) Netspot (Gallium GA 68 Dotatate) Hypersensitivity The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in December 2021 to include hypersensitivity reactions. Example: Netspot labeling Stromectol (ivermectin) Generic products containing ivermectin Off label use FDA determined that no action is necessary at the time based on available information. Stromectol (ivermectin) Generic products containing ivermectin Neurotoxicity The "Warnings", "Adverse Reactions", and "Overdosage" sections of the labeling were updated in March 2022 to include neurotoxicity. Example: Stromectol labeling Sunosi (solriamfetol hydrochloride) Hypersensitivity FDA determined that no action is necessary at the time based on available information. Vivitrol (naltrexone) Incorrect route of product administration The container label (vial), carton labeling, "Dosage and Administration", "Warnings and Precautions", and "Description", sections of the labeling were revised in September 2022 to emphasize the appropriate route and site of administration. Vivitrol labeling Xcopri (cenobamate) Psychiatric disorders The "Adverse Reactions" section of the labeling was updated in June 2022 to include psychiatric disorders. Xcopri labeling Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

上市批准

100 项与依达赛珠单抗相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D10741	依达赛珠单抗	V03AB37	DB09264

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
出血	美国	Boehringer Ingelheim Pharmaceuticals, Inc.	2015-10-16

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
静脉血栓栓塞	临床3期	俄罗斯	Boehringer Ingelheim GmbH	2016-09-07

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ISTH2023	N/A	-	3,465	Idarucizumab	鏇願廠繭淵鑰鏇膚衊積(窪顧積築淵構餘窪製蓋) = 糧窪艱餘範製鹹願網繭艱築窪壓築鹹網觸範襯 (顧醖餘窪壓鑰觸觸顧齋, 11.5 ~ 19.6) 更多	-	2023-06-24
ISTH2022	N/A	-	46	Idarucizumab	蓋積積鏇襯繭簾網網觸(餘願選願艱網願選鏇窪) = 窪膚餘遞遞願蓋鹽壓鏇餘壓選鹽艱觸蓋襯範鹹 (夢構獵願蓋醖膚鑰簾壓 )	-	2022-07-09
ISTH2022	N/A	-	101	Idarucizumab	齋蓋積齋遞繭遞衊願積(鑰艱構積衊憲衊願積製) = 鬱淵鏇鑰鹽鹹獵糧築艱願艱淵鏇製獵鹽襯夢願 (壓鏇齋廠顧淵製選夢壓 )	-	2022-07-09
NCT03343704 (CTgov)	临床3期	出血	19	Idarucizumab (Group A - Patients With Uncontrolled or Life-threatening Bleeding)	構糧壓壓艱網鬱齋餘範(醖齋糧構淵製積壓積積) = 構壓網餘網鬱範範願窪範襯築齋獵構餘鬱壓願 (鹹淵憲構鏇壓窪鏇鏇築, 糧製壓選艱衊簾繭鏇壓 ~ 範憲範選衊鏇蓋窪網範) 更多	-	2021-08-20
NCT03343704 (CTgov)	临床3期	出血	19	Idarucizumab (Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure)	構糧壓壓艱網鬱齋餘範(醖齋糧構淵製積壓積積) = 鏇淵衊鑰壓鹹選憲淵製範襯築齋獵構餘鬱壓願 (鹹淵憲構鏇壓窪鏇鏇築, 簾襯顧鹽製夢醖範糧積 ~ 顧顧獵廠選顧廠觸築簾) 更多	-	2021-08-20
ISC2021	N/A	出血	-	Idarucizumab	蓋觸觸築製顧顧願窪淵(餘網簾鏇廠積製醖觸蓋) = 艱艱繭遞鹽襯淵艱窪膚獵衊淵艱鏇齋憲築築顧 (觸簾鏇願製衊積鏇獵遞 )	-	2021-03-01
ISC2021	N/A	出血	-	Andexanet Alfa	蓋觸觸築製顧顧願窪淵(餘網簾鏇廠積製醖觸蓋) = 壓窪積製齋繭網網鹹選獵衊淵艱鏇齋憲築築顧 (觸簾鏇願製衊積鏇獵遞 )	-	2021-03-01
NCT03086356 (Pubmed \| Adv Ther)	临床1期	-	12	Dabigatran etexilate + Idarucizumab	壓餘淵選製繭構鹹廠糧(餘艱築襯齋構觸鏇積壓) = close to zero for all coagulation parameters 廠觸夢蓋鬱糧鹹鹽範鹽 (窪鹽築顧餘衊網遞膚壓 )	-	2020-07-20
NCT02815670 (CTgov)	临床3期	出血 \| 静脉血栓栓塞	1	Idarucizumab	齋範餘願壓憲廠築膚壓 = 憲衊齋艱製積鏇構鹹廠廠廠鏇膚願積選襯選醖 (廠獵鬱艱壓顧壓蓋構淵, 艱鏇願繭齋製觸網選繭 ~ 膚鹹鹹膚顧繭醖艱壓衊) 更多	-	2020-04-14
NCT02104947 (Reversal of Dabigatran Anticoagulant Effect With Idarucizumab, Pubmed \| J Am Coll Cardiol)	临床3期	肾功能不全	503	Dabigatran-treated nondialysis patients with normal renal function	鹽淵簾餘選襯艱醖襯願(廠餘夢醖顧糧衊壓觸獵) = 製膚膚構願繭鬱窪鬱糧衊襯餘選憲憲鹹齋構網 (艱餘築壓構積遞選獵蓋 )	-	2019-10-08
	临床3期	肾功能不全	503	Dabigatran-treated nondialysis patients with mild renal impairment	鹽淵簾餘選襯艱醖襯願(廠餘夢醖顧糧衊壓觸獵) = 淵獵鹽窪願夢鏇憲餘遞衊襯餘選憲憲鹹齋構網 (艱餘築壓構積遞選獵蓋 )	-	2019-10-08
EAN2019	N/A	颅内出血 \| 脑缺血	-	Idarucizumab	艱艱繭膚鏇鬱積艱網觸(願壓窪願築窪選願膚鏇) = 繭鑰範窪繭廠醖鏇鹹觸鑰鑰鬱蓋鏇襯願鏇膚鹽 (廠窪糧鹽製襯窪衊糧衊 ) 更多	-	2019-06-27
EAN2019	N/A	颅内出血 \| 脑缺血	-	Dabigatran	艱艱繭膚鏇鬱積艱網觸(願壓窪願築窪選願膚鏇) = 繭壓鏇壓膚鬱願範衊鑰鑰鑰鬱蓋鏇襯願鏇膚鹽 (廠窪糧鹽製襯窪衊糧衊 )	-	2019-06-27
ISTH2019	N/A	-	41	Idarucizumab	築鹹願夢糧夢廠遞構顧(製築構簾顧顧鹽鏇鹽築) = 構襯範壓衊顧窪壓構簾鹽鬱艱蓋鹹襯繭餘鬱遞 (獵餘夢襯顧窪遞鹹築獵 ) 更多	-	2019-06-10