Research Title：Adult and adolescent hemophilia patients treated with Marstacimab: a patient Experience Registry (AMBER) Protocol Number：94250855 Protocol Version Number：version 0.3 Date：15-November-2024 Leading site：Institution of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences Active Pharmaceutical Ingredient：a human IgG1 monoclonal antibody that targets the tissue factor pathway inhibitor (TFPI) Drug Name Generic name: marstacimab-hncq Purpose of the Study Primary Objectives:To quantify patient preferences for subcutaneous versus intravenous (IV) injection using the Marstacimab-Patient Preference Questionnaire (M-PPQ) after 1 month of marstacimab for routine prophylaxis treatment.
To assess the treatment burden using the Hemophilia Treatment Experience Measure (Hemo-TEM) in hemophilia patients after 6 months of marstacimab for routine prophylaxis treatment.
Exploratory Objectives:
To evaluate the annualized bleeding rate (ABR) of different types of bleeds after 6 months of subcutaneous marstacimab injections in hemophilia patients.
To assess changes in joint status scores between baseline and the final visit after 6 months of subcutaneous marstacimab injections in hemophilia patients, using the Hemophilia Early Arthropathy Detection with Ultrasound in China (HEAD-US-C).
To evaluate patient preferences regarding treatment experience via M-PPQ after 6 months

开始日期2026-02-15

申办/合作机构-

NCT07161687

/ Active, not recruitingN/A

HYMPAVZI S.C. INJECTION 150 MG PEN SPECIAL INVESTIGATION

A study to evaluate the safety of Hympavzi under the actual use in patients with congenital hemophilia who do not have inhibitors.

开始日期2025-10-30

申办/合作机构

Pfizer Inc.

NCT06703606

/ Recruiting临床1期

A PHASE 1B OPEN-LABEL NON-RANDOMIZED STUDY TO ASSESS THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF MARSTACIMAB TREATMENT FOLLOWING THE DISCONTINUATION OF EMICIZUMAB THERAPY IN ADOLESCENT AND ADULT PARTICIPANTS WITH SEVERE HEMOPHILIA A WITHOUT INHIBITORS.

The purpose of the study is to learn about safety, how the body processes marstacimab and how it works in patients with severe hemophilia A without inhibitors. Hemophilia A is rare bleeding disorder where the blood doesn't clot normally. This causes a person to bleed a lot, even from a small cut.
These patients who are on emicizumab medicine for routine prophylaxis for at least 6 months, and desire to switch to marstacimab medicine. Inhibitors are antibodies that the immune system develops because it sees the infused clotting factor as a foreign substance that needs to be destroyed. Antibodies are proteins that eat up the activated factor before it has time to stop the bleeding. Prophylaxis are preventive medicines.
This study is seeking for participants:
* with severe Hemophilia A withouth inhibitors who are on emicizumab treatment for at least 6 months.
* must be 12 to less than 75 years old
* must have a body weight of at least 35 kilograms. The results from this study will serve as a guide to doctors and their hemophilia A patients who will change their medicines in the real-world clinical setting. Patients who can take part in the study will receive marstacimab medicine as weekly injections under the skin of 150 milligrams for 4 months. Study treatment with marstacimab will be initiated no earlier than 14 days after last dose of emicizumab. The study can last up to 6 months. The sponsor will provide marstacimab. Patients will continue their usual treatment with the infused clotting factor for their bleeds when taking part in the study. Roll-over into an optional study treatment extension period will be available to participants who wish to continue prophylaxis with marstacimab in countries where it is not commercially available.

开始日期2025-05-13

申办/合作机构

Pfizer Inc.

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100 项与马塔西单抗相关的专利（医药）

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项与马塔西单抗相关的文献（医药）

2026-08-01·JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Management of breakthrough bleeds and surgical procedures in participants with hemophilia A or B without inhibitors receiving marstacimab prophylaxis in the phase 3 BASIS study

Article

作者: Matino, Davide ; Taylor, Carrie Turich ; Gould, Travis ; Palladino, Andrew ; Mahlangu, Johnny ; Sun, Pengling ; Kim, Hae Kyung ; Benítez Hidalgo, Olga

BACKGROUND:

Marstacimab, a subcutaneous antitissue factor pathway inhibitor monoclonal antibody, has demonstrated efficacy in reducing treated bleeds in severe hemophilia A or moderately severe to severe hemophilia B without inhibitors in the phase 3 BASIS study. Evidence guiding management of breakthrough bleeds and perioperative hemostasis during marstacimab prophylaxis remains limited.

OBJECTIVES:

Describe the frequency, treatment, and outcomes of breakthrough bleeds and surgical/medical procedures in participants without inhibitors receiving marstacimab prophylaxis.

METHODS:

After the 6-month observation phase, participants received a 300 mg marstacimab loading dose followed by 150 mg once-weekly in a 12-month active treatment phase (ATP). Bleed incidence, factor replacement therapy (FRT) use, and perioperative management were analyzed descriptively due to the small sample size and event distribution RESULTS: Of 116 participants in the ATP, 75 (64.7%) experienced 453 acute breakthrough bleeds and were treated with FRT; 83% were controlled with a single infusion, most often standard half-life recombinant or plasma-derived factor VIII/IX. Thirteen participants underwent 15 procedures (8 dental and 7 other), with marstacimab continued in 86.7% and FRT used in 13 of 15 (86.7%). No thromboembolic events occurred during ATP.

CONCLUSION:

Breakthrough bleeds were generally controlled with standard FRT, with most requiring only 1 infusion. Perioperative management of minor procedures was feasible without interruption of marstacimab, with FRT use comparable with other nonfactor prophylactic agents. Data on major surgery are lacking due to study exclusions, and conclusions should be restricted to minor and dental procedures. Further studies are needed to define perioperative protocols for higher-risk interventions.

2026-06-01·Therapeutic Advances in Hematology

A plain language summary of the BASIS study looking at people living with severe hemophilia A or B with inhibitors and being treated with marstacimab

作者: Mahlangu, Johnny ; Raje, Sangeeta ; Matino, Davide ; Agathon, Delphine ; Acharya, Suchitra S. ; Palladino, Andrew ; Gould, Travis ; Taylor, Carrie Turich ; Sun, Pengling

Summary:

What is this summary about? This summary describes a clinical study looking at how well marstacimab works in people living with hemophilia with inhibitors. The study was published in the medical journal Blood . Hemophilia is caused by not having enough blood clotting factors, which are proteins found in the blood that help form a clot and stop bleeding. People living with hemophilia either don’t make these proteins, have low amounts of these proteins, or these proteins do not work well. Hemophilia is usually inherited from biological parents, meaning it is passed on to their children through genes. In some cases, hemophilia happens even if no one in the family has it. There are some treatments to replace the missing clotting factor. This type of treatment is called factor replacement therapy and contains the missing clotting factor proteins. Some people make antibodies against the replacement clotting factors, so the replacement clotting factors do not work as well as they need to for the blood to clot. This is called hemophilia with inhibitors.People who have hemophilia with inhibitors need to take medicines called bypassing agents instead of replacement clotting factors. These medicines aim to activate the body’s blood clotting system, but do not always work well. They also need to be injected into a vein, known as intravenous infusion, or IV infusion for short. IV infusions are taken several times a week.Different options to IV factor replacement therapy for people living with hemophilia A or hemophilia B are called non-factor replacement therapy. A protein in the blood called Tissue Factor Pathway Inhibitor, or TFPI, can also prevent blood clotting. Marstacimab is a type of non-factor replacement therapy that attaches to TFPI and stops its activity. For people living with hemophilia, marstacimab can help blood to form a clot when needed. Marstacimab is injected under the skin. This can be an easier way to receive medicine than an injection into a vein. Marstacimab offers a new way to treat people living with hemophilia.What were the results of the study?The study showed that people living with hemophilia with inhibitors who were treated with marstacimab had fewer bleeding events over 1 year compared to previous therapy with bypassing agents. Most side effects with marstacimab treatment were minor or could be easily managed. One person stopped taking marstacimab treatment because they developed a skin rash that got better over time.What do the results mean?The study showed that marstacimab could help prevent bleeding in people living with hemophilia A or B with inhibitors.

2026-05-01·Therapeutic Advances in Hematology

Effect of marstacimab in young people living with severe hemophilia A or moderate to severe hemophilia B without inhibitors: A plain language summary from the BASIS study

作者: Patel, Priya

Summary:

What is this summary about?This summary describes a study that looked at how well the study treatment (marstacimab) works in people living with hemophilia. The summary describes how well marstacimab reduced bleeding episodes in young people (adolescents) 12 to 17 years old.Hemophilia is a condition that causes people to bleed more easily because their blood is unable to clot properly. Clotting is when blood turns from liquid into gel to stop bleeding. Hemophilia is caused by not having enough blood clotting factors, which are proteins found in the blood that help in forming a clot and stop bleeding. People living with hemophilia either don’t make these proteins, have low amounts of these proteins, or their proteins do not work well. There are different types of hemophilia, depending on which clotting factor is affected. For example, people living with hemophilia A lack clotting factor 8, and people living with hemophilia B lack clotting factor 9.Some treatments for hemophilia work by replacing clotting factors. These treatments are called factor replacement therapy, and are given directly into a vein (called intravenous, or IV for short). They are given frequently, sometimes even more than once a week. In some people living with hemophilia, the body develops antibodies called inhibitors that block replacement clotting factors from working properly. Not all people living with hemophilia produce these antibodies – those who don’t are classified as having hemophilia without inhibitors.A different way to treat people living with hemophilia is by using treatment called non-factor replacement therapy. One type of non-factor treatment called marstacimab is given as a regular preventive treatment (called prophylaxis). It works without replacing the missing clotting factors but brings blood clotting and bleeding back to a normal balance.Marstacimab is given once a week as a flat-dose (not based on body weight) injection under the skin (called subcutaneous) using an auto-injector device. This injection is sometimes called a shot and can be easier than injecting directly into a vein. In some cases, marstacimab can be taken less often than clotting factors. Marstacimab offers a new way to treat people living with hemophilia A or B without inhibitors.What were the results of the study?In this study, young people treated with marstacimab for 1 year had on average fewer bleeding episodes than on previous clotting factor replacement treatment. Marstacimab was well tolerated in young people (similar to adults), which means that most side effects that people had were mild to moderate and resolved by the end of the study.What do the results mean?This study showed that a once weekly injection of marstacimab could help reduce bleeding episodes in young people living with hemophilia A or B, without inhibitors.

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项与马塔西单抗相关的新闻（医药）

2026-09-17

·微信

国产血友病新药SR604进入III期临床，4类出血性疾病一份药搞定！

2026 年 9 月 16 日，上海莱士公司发布公告——SR604 注射液 III 期临床试验已在国家药品监督管理局药物临床试验登记与信息公示平台完成登记（方案编号：LS-SR604-AB-Ⅲ01）。这是中国第一款进入 III 期的靶向活化蛋白 C（APC）的非因子血友病新药——同时也是全球第一个进入 III 期的同靶点药物。 SR604 是国产原研、First-in-class、全新靶点三重身份叠加的产物。我读完上海莱士官方公告，再结合 III 期公示方案与 I/II 期公开数据，给你拆解 5 个关键看点。国内血友病的真实负担：治疗频次是一道隐形门槛国内血友病的"补凝血因子"方案已经走了几十年，但频次门槛始终没解决。 "传统凝血因子规律替代治疗给药频次较高，通常每周需静脉注射 1-3 次，患者长期输注负担重，临床对更长给药间隔的新药存在明确需求。" 每周 1-3 次静脉——这条隐形的频次门槛决定了两件事：血管脆化——长期静脉穿刺让静脉条件变差，最终扎不进；依从性崩溃——成人患者工作 / 出行 / 家庭节奏被打断，规律替代治疗的国内覆盖率只有 7%（成年患者）。备注：本文作者按公告原文引用时，将"预防治疗"统一表述为"规律替代治疗"——这是 2025 版《血友病治疗中国指南》的官方术语更新。 "频次"是血友病治疗里被低估的痛点。不是不想治，是治疗节奏绑死了日常生活。解药来了：非因子"再平衡"的 4 个开关公开报道梳理了一个清晰的框架——非因子"再平衡"药物已经在过去几年集中登场： "这几年出来一批"再平衡"类的新药，思路变了——不补凝血因子，而是去调一调抗凝这一头，让两边重新对上。" 过去 3 个已上市/在研的非因子再平衡药物：药物靶点公司给药艾美赛珠单抗（舒友立乐®）FVIII 模拟物（替代缺失凝血因子）罗氏每周 / 2-4 周皮下马塔西单抗（友瑞宁®）抗 TFPI （抑制外源性凝血抑制）辉瑞每周皮下芬妥司兰钠（赛菲因®）抗 AT （抑制最重要的抗凝蛋白）赛诺菲每 2 个月皮下注意：艾美赛珠是"FVIII 模拟物"，它仍然在"补"——逻辑上不算严格意义上的"再平衡"。真正和"再平衡"严格对应的是后两者（马塔西单抗 + 芬妥司兰）——抑制抗凝一端。现在 SR604 来了，把"再平衡"推到第 4 个开关—— 药物靶点公司给药SR604 （在研）抗 APC （抑制 APC 的抗凝功能）上海莱士每 4 周皮下（公示方案） 4 个开关对应 4 个不同的抗凝靶点——AT、TFPI、FVIIIa（被 APC 降解）、FVa（被 APC 降解）。关键 1：靶向 APC 有什么不一样？为什么说 SR604 的靶点"新"？ "血友病患者缺的是凝血因子 Ⅷ 或 Ⅸ。凝血这头本身就弱，刹车那头却没怎么动，两边一失衡，就成了动不动就出血的体质。" 人体凝血有 4 大套刹车系统：抗凝血酶（AT）—— 抑制 FXa 和凝血酶（芬妥司兰的靶点） TFPI —— 抑制外源性凝血启动（马塔西单抗的靶点） APC（活化蛋白 C）—— 切割 FVa 和 FVIIIa，让凝血不会刹不住车蛋白 S —— APC 的辅因子 APC 这套刹车在血友病患者身上"过度制动"——本来凝血就弱，APC 还在切割 FVIIIa，让凝血酶生成进一步减弱。英国剑桥大学 2017 年发表在 Current Opinion in Hematology 的综述（Polderdijk 等）解释了靶向 APC 的科学依据——综述指出，靶向 APC 是合理的血友病治疗路径，基于两点：生物学验证——FV Leiden 突变（一种 FV 基因自然突变，让 FVa 抵抗 APC 切割）的携带者，血友病出血表型显著减轻——"相当于大自然自己做过这个实验"。空间分隔的安全性——APC 既有抗凝功能，又有抗炎信号功能；但两者在空间和动力学上是分隔的——可以只抑制抗凝功能，不影响抗炎信号。这是 SR604 区别于其他非因子药物的科学基础——它不是改个剂型或延长半衰期，是从机制上另开了一条路。关键 2：IIb 期数据：年化出血率下降 90% 以上 + 关节炎症信号公开资料显示 IIb 期数据： "IIb 期在血友病 A/B 患者里，拟用 0.4mg/kg、每 4 周皮下打一次，24 周后年化出血率比基线下降 90% 以上。" 90% 以上下降——这是个什么水平？参照武汉会议唐亮讲的芬妥司兰 ATLAS-OLE 数据：整体中位 ABR 3.7（vs 因子方案 32 次/年，降幅 88%） 47.2% 患者 0-1 次出血 SR604 IIb 期 24 周的"90% 以上下降"和芬妥司兰 III 期 ATLAS 的"88%"基本同一量级——这是非因子再平衡药物的"基准线"。更值得注意的是另一个信号： "IIb 期的数据里还提到，它在降出血的同时，观察到一些和关节炎症相关的指标在好转。" 关节炎症好转——这超出了"减少出血"的基本目标。血友病患者的长期困扰是反复关节出血导致的慢性关节炎——如果一个药既能降出血、又顺带改善关节炎症，意义不只是"少扎针"。当然，这种提醒值得留意："这是 II 期看到的信号，III 期会不会继续成立，还要看。"关键 3：每 4 周皮下——一次皮下等于一次就诊上海莱士公告披露的 III 期方案核心参数： 0.4 mg/kg、每 4 周皮下注射 1 次多中心、单臂设计每 4 周皮下——3 个关键意义：告别静脉——从"扎血管"变成"扎肚皮"，血管脆化的患者也能用。频次接近长效——4 周 1 次 vs 因子方案 1 周 1-3 次，频次减少 75%。可能更长——公开资料显示："I/II 期的数据里探索过更长的间隔，公开资料里有的剂量方案最长说能到 8 周，也就是差不多两个月。" 如果最终按 8 周批准——每年扎针次数从一百多次降到个位数——这一判断是："这个差别是生活质量级别的，不是疗效数字级别的。"关键 4：适应症清单挂得长——这一条最有想象空间 III 期公示的核心适应症是血友病 A/B 患者出血发作的规律替代治疗——但上海莱士公告透露了 SR604 拓展适应症的版图：血友病 A——含不伴抑制物（III 期）血友病 B——含不伴抑制物（III 期）先天性凝血因子 Ⅶ 缺乏症——罕见中的罕见（I/IIa 期 24 周零出血）+ 已纳入国家药监局"关爱计划—延伸"试点项目血管性血友病（vWD）——II 期对比已上市的非因子药物： "现在已上市的几款非因子药，基本都围着血友病 A 和 B 转，vWD 和凝血因子 Ⅶ 缺乏症这块，多数药要么没碰，要么还在很早期。" SR604 的想象空间——一个靶点，覆盖一大片出血性疾病。对患者来说，意味着以后不同病种的病友可能用的是同一类药，不用每个罕见病单独等一个药。但这种提醒也很关键： "当然，名单长不等于都能批。每个适应症都是单独的临床，每个都要单独证明有效和安全。"关键 5：从 III 期到患者用上——还有几年现实路线图（公开报道 + 上海莱士公告综合）：阶段时间估计III 期临床（已启动） 1-2 年获批上市（待） III 期成功后再 1 年左右医保谈判 / 国谈（待）上市后再 1-2 年艾美赛珠单抗是参照系——公开资料显示： "艾美赛珠单抗 2018 年进中国，到现在还没进国家医保目录，2026 年还在等国谈的消息。" 一个 2018 年进中国的非因子药物，到 2026 年还在等国谈——SR604 即便一路顺利，乐观估计也要好几年才能进医保。上海莱士的角色——这是 SR604 的另一层意义：上海莱士原本是中国血液制品（白蛋白、静丙、凝血因子）巨头——主营业务是从血浆里提取凝血因子。SR604 是它从血液制品向创新生物药战略升级的"第二增长曲线"。公告原话： "至此，SR604 这款 First-in-class 在研药正式从剂量探索阶段进入确证性临床研究阶段，上海莱士从血液制品向创新生物药战略升级的"第二增长曲线"也迎来关键验证节点。"反思：国产原研的 3 个隐形门槛 SR604 是"国产原研 + First-in-class + 适应症挂得长"——这是过去 5 年国产血友病新药里少见的组合。但 III 期到上市到医保，每一步都有门槛。门槛 1：III 期数据能否复制 IIb 期的惊艳客观规律提醒："II 期和 III 期之间数据掉下来的药，这个领域里有不少。" IIb 期 24 周年化出血率下降 90% 以上——这是 IIb 期的结论。III 期入组患者更多、随访更长，数据能否复制是最大门槛。门槛 2：从生物制品巨头到创新生物药公司的转型上海莱士主业是血浆提取——这是制造业基因。SR604 是单克隆抗体——这是生物药基因。从"做血浆"到"做单抗"的转型，对生产工艺、质控体系、研发人才都是全新考验。门槛 3：从 III 期到医保的时间成本艾美赛珠单抗参照系告诉我们要等 8+ 年。有抑制物的成年患者、农村病友、等着做手术的病友，确实等不起——这是非因子药物普及的系统性问题，不只是 SR604 一个药的问题。但 SR604 这条路走通了——意味着国产血友病新药有能力在"全新靶点"上做出全球第一。最终判断是："国产原研、全新靶点、适应症挂得宽"——这种故事在血友病这个小领域里，确实不多见。参考来源：上海莱士SHRAAS《SR604获批Ⅲ期临床试验，上海莱士创新药布局取得关键性进展》 — 文章推荐 — 血友病儿童家长必看｜颅内出血30倍、关节畸形70%、三代试管32岁分水岭…… 血友病基因治疗多少钱、谁能做、要准备什么｜直播答疑汇总 — 视频推荐 — 读到这里，如果你觉得这篇文章对你有所帮助： ✨划线收藏重要知识点，方便日后查阅 💬留言分享你的疑问、经验与感受，大家一起交流 🔁分享转发给身边血友病病友、家属或微信群 👍点赞点一个赞，表达你的认可 ❤️推荐点亮支持，鼓励持续创作 💰赞赏用于持续整理、更新血友病相关科普你的每一次互动，都能让这份血友病科普被更多需要的人看见，帮助更多家庭少走弯路。

2026-09-05

·赛柏蓝

2026国谈下午场！恒瑞、辉瑞、信达...

9月5日下午，2026年医保谈判继续进行。 13时15分左右，下午场参与谈判的企业代表陆续抵达现场，包括先声药业、浙江京新药业、恒瑞医药、诺和诺德、辉瑞、信达药业、勃林格殷格翰（中国）、通化金马等。从企业构成来看，下午场外资药企参与度有所提升。其中，诺和诺德、辉瑞、勃林格殷格翰（中国）等跨国药企代表现身现场。从通过形式审查的产品来看，浙江京新药业涉及苯磺酸氨氯地平口崩片、盐酸卡立哌嗪胶囊；恒瑞医药涉及鲁兹诺雷钠片、泽美妥司他片等；辉瑞涉及马塔西单抗注射液、埃诺格鲁肽注射液等；勃林格殷格翰（中国）涉及那米司特片、宗艾替尼片等。（注：上述企业及产品仅代表通过形式审查情况，并不意味着相关产品均进入今日下午医保谈判环节，具体谈判品种仍以官方公布信息为准。）截至13时25分，下午参与谈判的企业代表已全部进入会场。此前，经过一上午的医保谈判，已有部分企业代表陆续离开会场。赛柏蓝现场了解到，今年医保谈判流程安排较往年或有所变化。相关药企人员表示，今年医保局整体安排更加灵活，谈判时间有所提前，也为企业后续工作安排预留了更多空间。与往年类似，谈判结果依然是企业最为谨慎的话题。面对媒体询问，多数离场企业代表选择微笑、摆手，并未透露谈判情况。会场外，仍有不少药企代表等待接应，其中一位企业代表表示：“有点紧张，汗都出来了。” 来源｜赛柏蓝现场｜晓琳文字｜亿路

2026-08-28

·海百生物

靶点介绍04 | 组织因子（Tissue Factor）深度研究（下）：凝血之始，肿瘤之靶

靶点介绍靶向治疗的黄金时代： TF-ADC与抗TFPI抗体的临床竞速中篇，我们解析了TF作为信号受体驱动肿瘤进展的分子网络。当靶点的生物学被充分阐明，临床转化的逻辑便自然浮现：同一个TF通路，可以导向两种截然不同的治疗策略，在肿瘤侧阻断其表达，在凝血侧解除其抑制。本文将聚焦这两条已进入收获期的抗体赛道，剖析从分子设计到临床验证的完整路径。双轨并行：同一个靶点，两种治疗逻辑基于对TF通路生物学功能的深入理解，靶向治疗沿着两条截然不同的抗体路径展开。子赛道A：TF-ADC（肿瘤治疗）利用肿瘤细胞表面TF的高表达，将细胞毒性载荷精准递送至肿瘤部位。正常组织中TF主要定位于血管外周，不与血流直接接触，这一表达差异为ADC提供了安全窗口。核心逻辑是“抗体导航、载荷杀伤”。子赛道B：抗TFPI抗体（血友病治疗）通过抑制TF凝血途径的天然“刹车”TFPI，增强血友病患者残存的凝血能力。核心逻辑是“功能再平衡”。两条赛道共享对TF通路分子机制的深刻认知，却在治疗目标上截然相反：一个要消灭表达TF的肿瘤细胞，一个要恢复被TFPI过度抑制的凝血功能。这种“同靶异治”的范式在药物开发史上并不多见，也体现了基础研究的深度如何决定临床转化的广度。 TF-ADC：从First-in-class到治疗窗口的瓶颈 TF-ADC的成败取决于抗体表位、内吞效率和连接子-载荷系统三个要素的协同。Tisotumab vedotin（TIVDAK）作为全球首个获批的TF-ADC，其设计体现了对每个要素的精密考量。抗体表位：抗体组分hTF011的表位位于TF胞外域C端FnIII结构域，该位置是TF-FVIIa相互作用的关键区域，抗体结合后可竞争性抑制FVIIa结合，同时诱导强烈的受体介导内吞。人源化过程中，框架区经过回复突变优化，以恢复亲和力并降低免疫原性。连接子-载荷系统：连接子采用蛋白酶可裂解的缬氨酸-瓜氨酸（Val-Cit）二肽，在血浆中稳定，在溶酶体组织蛋白酶B环境中高效裂解。载荷为微管抑制剂MMAE，药物抗体比（DAR）约为4。图1 Tisotumab vedotin作用机制 TIVDAK的获批基于InnovaTV 204和InnovaTV 301两项关键试验。 InnovaTV 204为单臂II期试验，在101例既往接受过治疗的复发或转移性宫颈癌患者中取得24%的客观缓解率，中位缓解持续时间为8.3个月。基于这一数据，2021年FDA授予加速批准。 InnovaTV 301为III期验证性试验，2024年发表于NEJM。研究纳入502例患者，结果显示TIVDAK较研究者选择的化疗显著改善总生存期：中位OS为11.5个月 vs 9.5个月，死亡风险降低30%。无进展生存期和客观缓解率亦显著优于化疗。图2 InnovaTV 301试验总生存期曲线。然而，MMAE的脱靶毒性限制了TIVDAK的治疗窗口。眼部毒性（结膜炎、干眼、角膜炎，发生率约40%）和周围神经病变（发生率约30%）是最主要的剂量限制性毒性，约14.8%的患者因毒性停药。这一毒性谱与MMAE作为微管抑制剂的系统性暴露特性有关。Val-Cit连接子在循环中虽相对稳定，但并非完全不可裂解，游离MMAE的释放可导致非靶向组织的微管破坏。眼部毒性的机制尤为特殊：MMAE通过泪液排泄至结膜，直接损伤角膜缘干细胞。这一经验为新一代TF-ADC指明了方向：需要肿瘤选择性更高、治疗窗口更宽的载荷，以及更稳定的连接子系统来降低系统性暴露。抗TFPI抗体：亲和力悖论与再平衡策略 TFPI由三个Kunitz型蛋白酶抑制域构成，是外源性凝血途径的天然反馈抑制物。血友病A和B分别由FVIII和FIX的遗传性缺失导致，传统替代疗法面临抑制物产生和频繁静脉输注的瓶颈。抗TFPI抗体提供了一种全新的“再平衡”策略：通过解除TFPI对残存凝血能力的抑制，使血友病患者在不依赖外源性凝血因子的情况下恢复止血功能。图3 Marstacimab与TFPI-K2域的相互作用 Marstacimab（Hympavzi，辉瑞）的开发历程体现了抗体工程的关键权衡。其研发团队通过杂交瘤和噬菌体展示技术筛选抗体库，发现一个反直觉的规律：过高亲和力的抗体（Kd < 1 nM）因与TFPI形成过于稳定的复合物，反而被快速清除；中等亲和力（Kd约5.72 nM）的抗体具有更长的血浆驻留时间。这提示治疗性抗体的开发不是“越强越好”，而需要与靶点的生物学特性相匹配。Marstacimab采用全人源IgG1，Fc段经过优化以降低效应功能，避免对表达TFPI的内皮细胞产生不必要的细胞毒性。III期BASIS试验中，年化出血率降低91.6%，2024年10月获FDA批准，成为首个抗TFPI产品。 Concizumab（Alhemo，诺和诺德）针对“伴有抑制物”的最棘手人群，皮下注射每日一次，2024年获FDA批准。KN057（armocibart，康宁杰瑞）是中国首个自主研发的抗TFPI单抗，定位覆盖所有类型血友病的“泛用型”治疗，目前处于III期临床。下一代竞速：平台之战新一代TF-ADC围绕载荷升级、连接子优化和抗体工程三个维度展开，本质上是抗体工程平台的竞速。载荷升级：从MMAE到TOP1i 载荷升级是核心突破口。XNW28012（信诺维）是首个携带TOP1抑制剂载荷的TF-ADC。与MMAE不同，TOP1i通过诱导DNA双链断裂杀伤肿瘤细胞，对缓慢增殖的实体瘤可能更有效，且不易产生与微管抑制剂交叉的耐药。截至2025年11月，在313例患者的I/II期研究中，胰腺癌一线治疗ORR达47.6%。 ADCE-T02（Adcendo）采用exatecan-based载荷，抗体经过Fc沉默改造，2026年5月与MSD达成合作，计划联合Keytruda探索“ADC+PD-1”的协同策略。连接子优化：定点偶联实现DAR均一传统随机偶联产生DAR分布不均的混合物，导致药代动力学波动和脱靶毒性。SYS6051（石药集团）采用工程化半胱氨酸定点偶联，实现均一的DAR值（约2），2026年在中美两地获批临床。 STRO-004（Sutro Biopharma）采用非天然氨基酸定点偶联技术，在抗体特定位置引入对乙酰苯丙氨酸，通过肟键与载荷连接，实现精确的DAR控制。其DAR8 exatecan设计在临床前模型中显示出较第一代TF-ADC显著拓宽的治疗窗口。图4 新一代ADC技术平台：均一化双载荷设计结语：格局与展望 TF-ADC赛道正处于从“First-in-class”到“Best-in-class”的演进期。未来3至5年的关键趋势包括：TOP1i载荷取代微管抑制剂成为主流；位点特异性偶联技术提升均一性；以及“ADC+IO”联合策略的验证。胰腺癌可能成为突破性适应症，TF在PDAC中的高表达率（>90%）和当前治疗的匮乏，使其成为理想的“首发战场”。图5 ADC临床试验全球增长趋势（2006—2022）抗TFPI抗体赛道已进入商业化竞争阶段。Marstacimab的血栓风险（2025年报告一例长期用药患者术后发生致死性血栓性卒中）提示，TFPI抑制的治疗窗口需要更精细的个体化管理。未来的方向包括Fc段改造以延长半衰期、双特异性抗体协同增强凝血，以及口服小分子TFPI抑制剂的开发。从19世纪中叶的组织提取物，到2026年多个抗体药物竞速临床，组织因子的故事印证了药物开发的核心逻辑：深刻的靶点认知是起点，精妙的分子设计是桥梁，而未被满足的临床需求是终点。TF这个百年靶点，正在迎来属于它的黄金时代！关于海百海百生物（HBind）成立于2016年5月，位于武汉市东湖高新区，是一家以“加速药物研发、守护人类健康”为使命，致力于创新生物药、抗体等各类靶向结合分子的开发和应用的高新技术企业，为全球创新药企和科研机构提供从抗原设计制备、抗体开发、筛选评价、工程化改造和生产的一站式抗体服务。团队现已成功完成900+项目，形成多种属全平台的抗体等靶向结合分子开发能力。涵盖人、鼠、兔、羊驼等15个物种，包含流式单B、噬菌体、酵母、细胞、mRNA展示、杂交瘤共六大技术平台。【往期精选】靶点介绍02 | Nectin-4深度研究（上）：一个靶点的起源、沉默与命运转折靶点介绍02 | Nectin-4深度研究（中）：从靶点验证到临床突破，竞争格局如何演变？靶点介绍02 | Nectin-4深度研究（下）：未来方向与关键问题靶点介绍03 | 靶点5T4的三十七年研究历程（上）：从癌胚抗原到多技术路线临床探索靶点介绍03 | 靶点5T4的三十七年研究历程（下）：从临床转化困境到未来突破方向【参考文献】 [1] BOC SCIENCES. Tivdak: FDA's first approved tissue factor-targeted antibody-drug conjugate[EB/OL]. (2021-11-11)[2026-08-21]. [2] VERGOTE I B, GONZALEZ MARTIN A, FUJIWARA K, et al. Tisotumab vedotin as second- or third-line therapy for recurrent cervical cancer[J]. N Engl J Med, 2024, 391(16): 1500-1510. [3] JIN M, HETT S, PATEL S, et al. Discovery and optimization of marstacimab, a human monoclonal antibody targeting tissue factor pathway inhibitor for the treatment of hemophilia A and B[J]. mAbs, 2026, 18(1): 2685362. [4] WEN M, YU A, PARK Y, et al. Homogeneous antibody-drug conjugates with dual payloads: potential, methods and considerations[J]. Int J Mol Sci, 2025, 26(13): 6969. [5] ZHOU W, XU Z, LIU S, et al. Landscape of clinical drug development of ADCs used for the pharmacotherapy of cancers: an overview of clinical trial registry data from 2002 to 2022[J]. BMC Cancer, 2024, 24: 898. [6] COLEMAN R L, LORUSSO D, GENNIGENS C, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study[J]. Lancet Oncol, 2021, 22(5): 609-619. [7] DE BONO J S, CONCIN N, HONG D S, et al. Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial[J]. Lancet Oncol, 2019, 20(3): 383-393. [8] CHAUVIN C, STROH M, HONG D S, et al. Tisotumab vedotin antibody-drug conjugate targeting tissue factor: dose selection and clinical pharmacology strategies[J]. Clin Pharmacol Ther, 2023, 113(5): 1014-1024. [9] DRAGO J Z, MODI S, CHANDARLAPATY S. Unlocking the potential of antibody-drug conjugates for cancer therapy[J]. Nat Rev Clin Oncol, 2021, 18(6): 327-344. [10] FU Z, LI S, HAN S, et al. Antibody drug conjugate: the "biological missile" for targeted cancer therapy[J]. Signal Transduct Target Ther, 2022, 7(1): 93. [11] TARANTINO P, RICCIUTI B, PRADHAN S M, et al. Optimizing the safety of antibody-drug conjugates for cancer therapy[J]. Nat Rev Clin Oncol, 2023, 20(8): 557-573. [12] MATINO D, ACHARYA S S, PALLADINO A, et al. Efficacy and safety of the anti-tissue factor pathway inhibitor marstacimab in participants with severe hemophilia without inhibitors: results from the phase 3 BASIS trial[J]. Blood, 2023, 142(Supplement 1): 285. [13] PANOWSKI S, BHAKTA S, RAAB H, et al. Site-specific antibody drug conjugates for cancer therapy[J]. mAbs, 2014, 6(1): 34-45. [14] DUMONTET C, REICHERT J M, SENTER P D, et al. Antibody-drug conjugates come of age in oncology[J]. Nat Rev Drug Discov, 2023, 22(8): 641-661. [15] BROZE G J, GIRARD T J. Tissue factor pathway inhibitor: structure-function and implications for hemophilia therapy[J]. Thromb Res, 2024, 235: S1-S4.

100 项与马塔西单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11261	-	-	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
血友病A	美国	Pfizer Inc.	2024-10-11
血友病B	美国	Pfizer Inc.	2024-10-11

未上市

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
中面发育不全，轻度至重度	临床3期	美国	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	日本	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	阿根廷	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	澳大利亚	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	奥地利	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	巴西	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	加拿大	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	捷克	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	丹麦	辉瑞投资有限公司	2022-12-09
中面发育不全，轻度至重度	临床3期	法国	辉瑞投资有限公司	2022-12-09

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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


NCT03938792 (BASIS, ISTH2026)	临床3期	血友病B \| 血友病A	3	Marstacimab	遞構鹽選鬱網顧鏇築廠(膚蓋醖網積鹹鬱膚艱選) = After 6 months, median change from baseline in patient-reported health-related quality-of-life endpoints was greater with marstacimab in the ATP vs prior RP in the OP, indicating greater improvement: Haem-A-QoL Physical Health domain (−10.0 vs −2.5), Haem-A-QoL total score (−27.6 vs 2.8), and Haemo-Qol total score (−15.6 vs −0.6). During the ATP, all participants reported adverse events (AEs), which were mild or moderate (Table 1). No serious AEs, deaths or thrombotic events were reported in this cohort. No participants had their marstacimab dose temporarily discontinued or modified and no participants discontinued the study due to AEs. No antidrug antibodies were detected in any of these participants. 夢壓壓衊獵網鑰艱膚鑰 (繭願獵憲構醖鹽艱憲齋 )	积极	2026-07-12
NCT03938792 (BASIS, ISTH2026)	临床3期	血友病B \| 血友病A	167	Marstacimab 300mg loading dose followed by once-weekly 150mg (Adults with inhibitors)	願壓範衊艱夢觸鏇壓夢(醖醖鬱網廠鏇繭鹽夢繭) = 鏇遞鹽憲醖廠選繭餘獵夢網醖齋鹽範鬱淵醖廠 (鬱鏇簾網醖觸夢選夢築 )	积极	2026-07-12
				Marstacimab 300mg loading dose followed by once-weekly 150mg (Adults noninhibitors)	網願觸觸膚鑰夢積餘醖(鏇選齋蓋願網簾窪齋獵) = 觸積窪遞願構蓋製願觸糧鏇糧憲鹹鹹築廠願糧 (願齋窪遞遞獵鏇鏇艱餘 ) 更多
NCT03938792 (BASIS, ASH2025)	临床3期	血友病B \| 血友病A	116	Marstacimab 300 mg SC	積網願積鑰糧蓋繭獵醖(壓壓鏇積簾顧鑰齋繭鹹) = 製鑰顧醖廠壓簾餘廠窪範糧蓋顧憲糧簾衊鏇獵 (觸築鑰顧鹽醖網觸獵餘, 5.52) 更多	积极	2025-12-06
NCT03938792 (BASIS, ASH2025)	临床3期	血友病B \| 血友病A	17	Marstacimab	鹹鹽餘鑰襯壓窪夢繭積(艱衊廠選憲淵淵鹽壓構) = 網遞網夢艱醖簾窪壓糧醖遞繭鹽網繭廠繭廠憲 (顧範齋齋艱鏇襯鹽艱膚 ) 更多	积极	2025-12-06
				prior routine prophylaxis	鹹鹽餘鑰襯壓窪夢繭積(艱衊廠選憲淵淵鹽壓構) = 窪鏇鏇簾壓積遞襯築鬱醖遞繭鹽網繭廠繭廠憲 (顧範齋齋艱鏇襯鹽艱膚 ) 更多
NCT03938792 (BASIS, BusinessWire) 人工标引	临床3期	血友病B \| 血友病A	-	Hympavzi	鏇艱壓積艱獵憲齋簾網(鑰襯構製齋廠憲鬱鹹範) = 鏇鑰窪觸範艱壓繭鏇憲鏇觸醖醖廠鏇繭醖網夢 (夢餘糧窪繭顧壓選艱膚 ) 达到	积极	2025-06-26
				on-demand treatment	鏇艱壓積艱獵憲齋簾網(鑰襯構製齋廠憲鬱鹹範) = 淵鏇餘夢顧廠衊觸鏇獵鏇觸醖醖廠鏇繭醖網夢 (夢餘糧窪繭顧壓選艱膚 ) 达到
ASH2024	N/A	血友病B \| 血友病A	-	Marstacimab 150 mg SC QW	構選鏇蓋憲鑰壓觸鏇壓(衊鹽糧顧糧廠鬱艱選網) = 觸觸遞簾範憲積窪窪簾網窪廠醖窪製觸壓襯窪 (鹽鏇觸築觸構齋蓋艱襯 )	-	2024-12-09
				Factor replacement therapy (OD or RP)	構選鏇蓋憲鑰壓觸鏇壓(衊鹽糧顧糧廠鬱艱選網) = 鑰膚遞顧淵窪艱壓艱製網窪廠醖窪製觸壓襯窪 (鹽鏇觸築觸構齋蓋艱襯 )
NCT03938792 (FDA_CDER) 人工标引	临床3期	血友病B \| 血友病A	66	On-Demand Factor-Based Therapy	鹽蓋衊範壓淵鏇淵獵鹽(網憲廠淵範餘窪廠觸構) = 夢廠膚醖窪醖廠獵淵淵鑰糧鑰淵淵蓋衊選觸衊 (鬱構顧繭蓋膚鏇鹽蓋鬱, 31.03 ~ 46.54) 更多	积极	2024-10-11
				HYMPAVZI Prophylaxis	鹽蓋衊範壓淵鏇淵獵鹽(網憲廠淵範餘窪廠觸構) = 鹽齋獵窪齋製廠衊壓艱鑰糧鑰淵淵蓋衊選觸衊 (鬱構顧繭蓋膚鏇鹽蓋鬱, 2.09 ~ 4.85) 更多
NCT05145127 (FDA_CDER) 人工标引	临床3期	血友病B \| 血友病A	-	On-Demand Factor-Based Therapy	遞齋築鬱衊繭淵顧顧艱(糧夢淵膚淵壓簾製鑰鬱) = 窪艱齋艱範願觸憲顧積憲鹹淵製積醖觸鏇製鏇 (繭襯壓窪鏇衊淵窪顧衊, 5.09 ~ 10.61) 更多	积极	2024-10-11
				HYMPAVZI Prophylaxis	遞齋築鬱衊繭淵顧顧艱(糧夢淵膚淵壓簾製鑰鬱) = 鏇網顧餘窪齋鹽範廠膚憲鹹淵製積醖觸鏇製鏇 (繭襯壓窪鏇衊淵窪顧衊, 3.40 ~ 6.77) 更多
NCT03938792 (BASIS, ASH2023) 人工标引	临床3期	血友病B \| 血友病A	128	Marstacimab (On Demand) (Observational Phase)	築獵構餘蓋範餘糧鏇鏇(積壓窪鹽窪淵壓齋構網) = 糧壓艱選窪憲淵膚繭繭簾壓艱廠憲廠窪製衊窪 (襯選襯繭壓構構鹽網膚, 31.03 ~ 46.54) 更多	积极	2023-12-09
				Marstacimab (Routine Prophylaxis) (Observational Phase)	築獵構餘蓋範餘糧鏇鏇(積壓窪鹽窪淵壓齋構網) = 網積襯獵鏇廠鑰簾鏇築簾壓艱廠憲廠窪製衊窪 (襯選襯繭壓構構鹽網膚, 5.09 ~ 10.61) 更多
NCT04878731 (CTgov)	临床1期	血友病	6	PF-06741086 (Marstacimab)	醖鏇願膚選憲網憲範積 = 齋壓顧廠衊壓繭蓋積築簾醖簾網觸糧願網糧夢 (積蓋構鏇鏇觸觸積鏇顧, 簾艱糧膚膚鹽鹹廠夢鏇 ~ 範簾鑰獵鹹範夢衊構夢) 更多	-	2023-07-07