A Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in the Treatment of Bleeding Episodes in Chinese Subjects Diagnosed With Von Willebrand Disease

The main aim of this study is to find out if VONVENDI is safe for adult Chinese participants with VWD. The study will also check how well VONVENDI helps control bleeding with or without product ADVATE in the participants who may need elective surgery or dental procedures. In addition, the study will also examine how VONVENDI is processed by the body (known as pharmacokinetic [PK]) and how the drug helps the body respond or improve a condition (pharmacodynamic [PD]).
Participants will receive an initial dose of VONVENDI of 40 to 80 international units per kilogram (IU/kg) of body weight. If a participant's baseline factor VIII (FVIII) level is not high enough to help stop bleeding, VONVENDI will be given along with 30 to 45 IU/kg of ADVATE rFVIII.
Participants will be in the study for approximately 14 months. During the study, participants will be followed up at clinics or over telephone calls.

开始日期2025-10-12

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT06864975

/ Recruiting临床4期IIT

Assessing Different FVIII Dose and Frequency in Immune Tolerance Induction (ITI) with ADVATE Among Hemophilia a Boys with Inhibitor (INITIATE Study): a Multicenter Open-label Non-randomized Clinical Trial

Hemophilia A is a blood coagulation disorder caused by deficient or dysfunctional clotting factor VIII (FVIII) leading to incomplete haemostasis. Patients with severe Hemophilia A are predisposed to recurrent bleeding episodes (BEs) in joints and soft tissues that culminate in debiltating arthropathy and long-term morbidity. Prophylaxis with plasma-derived or recombinant FVIII concentrates effectively restores FVIII levels in patients with Hemophilia A, and significantly reduces the risk of bleeding. A critical concern for patients receiving FVIII replacement therapy is the development of neutralising antibodies (inhibitors) against the treatment. Inhibitors develop in up to 40% of patients with severe Hemophilia A when first exposed to FVIII treatment, typically within the first 20-30 exposure days (EDs) although a residual risk remains until after 75 EDs. Inhibitors preclude the use of FVIII replacement therapy for prevention and treatment of bleeding.
Eradication of inhibitors therefore remains an important objective for Hemophilia A patients with inhibitors. Immune tolerance induction (ITI) therapy is the only clinically proven strategy for inhibitor eradication, and at least one attempt should be offered to patients with inhibitors. However, while ITI is well-studied and has a 60- 80% success rate, treatment regimens can be expensive and burdensome to patients.
There are limited data on the use of different dose regimen of FVIII ITI in China. The INITIATE Study was designed to observe treatment strategies in patients with hemophilia A with inhibitors, with a focus on evaluating the safety and effectiveness of different dose regimens of ITI. The INITIATE Study includes multiple groups to explore factors that may affect ITI outcomes, and to explore the effects of different treatment methods on patient ITI biomarkers (genomics, transcriptomics, proteins (antibodies).

开始日期2025-03-01

申办/合作机构-

NCT05582993

/ Recruiting临床3期

A Phase 3, Prospective, Open-label, Uncontrolled, Multicenter Study on Efficacy and Safety of Prophylaxis With Vonicog Alfa (rVWF) in Children Diagnosed With Severe Von Willebrand Disease

The main aim of the study is to evaluate the effectiveness of prophylaxis with vonicog alfa (recombinant von Willebrand factor [rVWF]) in children. This study will enroll those participants who have been previously treated with VWF product or with a plasma-derived VWF (pdVWF) product. In this study, participants will be treated with vonicog alfa (rVWF) for 12 months.
During the study, participants will visit the study clinic 5 times after treatment initiation.

开始日期2024-11-06

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

100 项与重组人凝血因子Ⅷ（Takeda）相关的临床结果

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100 项与重组人凝血因子Ⅷ（Takeda）相关的转化医学

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100 项与重组人凝血因子Ⅷ（Takeda）相关的专利（医药）

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项与重组人凝血因子Ⅷ（Takeda）相关的文献（医药）

2025-07-01·HAEMOPHILIA

Haemophilia Prophylaxis in the Age of Innovation: Exploring Opportunities for Personalized Treatment

Review

作者: Chamouard, Valerie ; Lienhart, Anne ; Pouplard, Claire ; Volot, Fabienne ; Desage, Stephanie ; Dargaud, Yesim

ABSTRACT:

Introduction:

Recent advancements in haemophilia treatment have introduced a range of innovative therapies, including activated FVIII mimetics, ultra‐extended half‐life recombinant FVIII, rebalancing agents and gene therapy. These developments have transformed treatment options and expanded prophylaxis strategies.

Aim:

This article reviews key criteria and personalization strategies for the optimization of prophylaxis, tailored to the unique needs of each haemophilia patient on an individual basis.

Discussion and Conclusion:

Although these new therapies offer significant promise in controlling bleeding and enhancing quality of life, challenges such as variable efficacy, potential long‐term risks and high costs remain. Additionally, the absence of validated surrogate markers for non‐factor therapies limits their optimal use in clinical settings.The primary goal of haemophilia care is to provide optimal personalized treatment that enables patients to lead unrestricted lives. However, the introduction of these novel treatments necessitates a shift in treatment paradigms and the development of improved evaluation tools for better personalization.Choosing the most appropriate treatment requires careful clinical follow‐up, taking into account patient preferences, disease burden, and individual and environmental factors that affect patients' lives. Ongoing research and real‐world studies are essential to assess long‐term efficacy and safety. In addition, improving educational resources—such as digital platforms, virtual reality tools and personalized educational materials tailored to patients' life goals—and effective patient engagement strategies will be critical to achieving successful treatment personalization and adherence.

2025-05-01·THROMBOSIS RESEARCH

FVIII half-life products: A real-world experience

Article

作者: Napolitano, Angela ; Simion, Chiara ; Simioni, Paolo ; Zanon, Ezio ; Porreca, Annamaria

BACKGROUND:

Haemophilia A is a genetic coagulation disorder requiring prophylactic Factor VIII (FVIII) treatment to prevent joint damage and enhance quality of life. The introduction of extended half-life (EHL) FVIII products represents a major advancement, addressing patient needs for reduced infusion frequency, improved efficacy, and enhanced safety.

METHODS:

This single-centre observational study examined the real-world use of FVIII products among 124 male patients treated at the Haemophilia Centre of Padua from January 2018 to December 2023. Data on patient characteristics, treatment regimens, and pharmacokinetic profiles were analyzed.

RESULTS:

Among the FVIII products used, Advate®, Elocta®, and Jivi® showed median half-lives of 11.25 [10.75-12.25], 16.50 [13.75-17.75], and 15.38 [13.38-18.63] hours, respectively. Esperoct® exhibited the longest half-life at 19.75 [16.00-24.50] hours, enabling reduced infusion frequency. EHL products showed significantly lower weekly infusion rates compared to standard half-life (SHL) products (1.4 [1.0-2.0] vs. 2.0 [2.0-3.0], p < 0.001), with comparable bleeding control among the different FVIII-EHL.

CONCLUSIONS:

EHL FVIII products offer significant clinical benefits, reducing the burden of frequent infusions and improving adherence while maintaining effective bleeding control. Despite these advancements, comprehensive evaluations of cost, safety, and long-term outcomes are essential to optimize their integration into haemophilia care.

2025-05-01·ADVANCES IN THERAPY

Efficacy and Safety of Recombinant Factor VIII in Previously Untreated and Previously Treated Children with Hemophilia A: A Systematic Review

Review

作者: Sun, Jing ; Wang, Zhenguo ; Zhou, Xuan ; Feng, Xiaoqin

INTRODUCTION:

Inhibitor development is a primary concern for pediatric patients with hemophilia A (HA) undergoing recombinant factor VIII (rFVIII) therapy, yet relevant research is lacking. We aimed to compare the efficacy and safety of standard (SHL) and extended half-life (EHL) rFVIII products in previously treated (PTPs) and untreated (PUPs) pediatric patients with HA.

METHODS:

Following PRISMA guidelines, we searched clinical studies from PubMed, Embase, and Cochrane Library. Data were extracted and a single-arm meta-analysis was performed.

RESULTS:

This systematic review included 16 studies involving 1145 patients. Three studies reported changes in annual bleeding rate (ABR); their results displayed no statistically significant difference in ABR changes in pediatric patients with HA after rFVIII treatment. Ten studies reported inhibitor development, nine focused on PUPs. Here, EHL rFVIII showed a proportion of inhibitors at 27.5% (95% confidence interval [CI] 22.6%; 32.6%), and third-generation SHL rFVIII showed a proportion of inhibitors at 36.4% (27.2%; 46.2%), with a high-titer proportion of 20.9% (12.9%; 30.3%) for the latter. Both SHL rFVIII (octocog alfa) and EHL rFVIII (rurioctocog alfa pegol) presented low proportions of inhibitor development. Octocog alfa exhibited the lowest high-titer inhibitor incidence, marked at 12.7% (5.3%; 24.5%). Eleven studies addressed adverse events (AEs), with octocog alfa showing low reported treatment-related AEs at a proportion of 14.5% (6.5%; 26.7%).

CONCLUSION:

Our analysis revealed that both octocog alfa and rurioctocog alfa pegol showed low inhibitor development, with octocog alfa having few treatment-related AEs. Regular monitoring for inhibitors during rFVIII therapy is important.

项与重组人凝血因子Ⅷ（Takeda）相关的新闻（医药）

2024-09-04

·武田中国

武田注射用重组人凝血因子Ⅷ剂量计算软件myPKFiT®3.0版本在中国正式获批

武田中国今日宣布，旗下注射用重组人凝血因子Ⅷ（FⅧ）剂量计算软件myPKFiT®的版本更新正式获得国家药品监督管理局（NMPA）批准。新版本包含医疗专业人士应用程序的优化，并首次新增针对个体患者的移动应用程序，方便患者维持和执行个体化给药方案，为其回归正常生活提供支持，并将进一步推动中国血友病领域个体化治疗的发展。血友病是一种罕见的遗传性出血性疾病1，主要是由于患者体内凝血因子缺乏或质量异常导致凝血障碍。目前，我国血友病患病率为2.73/100,0002，其中，A型血友病最为常见，大约占80%～85%2。A型血友病主要为凝血因子Ⅷ质或量的异常，在临床上，以关节、肌肉、内脏和深部组织自发性或轻微外伤后出血难以停止为特征2。如果不及时进行治疗，可能导致关节畸形和假性肿瘤等问题，严重者甚至危及生命。目前，血友病患者仍然需要终身进行治疗。通过长期的规范化治疗，患者能够有效避免发生出血以及出血造成的关节损伤等问题1。同时，由于个体差异性大，《血友病治疗中国指南（2020年版）》指出，A型血友病应根据患者年龄、静脉通路、出血表型、药代动力学（PK）特点以及凝血因子制剂供应情况，制定最佳的个体化方案3，进而有效避免治疗不足或治疗过度的情况。 myPKFiT® 是目前国家药品监督管理局唯一批准4的个体化预防性凝血因子FⅧ剂量计算软件，该软件与武田注射用重组人凝血因子Ⅷ（商品名：百因止®，于2013年在中国上市）配合使用，可结合每位A型血友病患者的个体药代动力学（PK）参数进行评估，针对不同患者的特征和需求个体化计算出FⅧ所需用量，有效避免治疗不足或过度治疗，持续改善患者的生活质量。2020年，myPKFiT®首次获得国家药品监督管理局批准正式进入中国，为中国A型血友病患者带来个体化治疗管理的创新选择。此次获批的myPKFiT®3.0版本在原版本基础上进行了相应的迭代更新，模型不变，同时更具可视化、便捷化和可交互的特点。新版本优化了医疗专业人士应用程序，方便医生能够更好地跟踪、检索患者的所有出血和输注的记录。同时，新增的患者移动应用程序适用于搭载有安卓及iOS操作系统的手机，使患者也能够实时查看其体内FⅧ水平的预估数值，以帮助其在医务人员的指导下做出活动决定。此外，该移动应用程序替换了原出血和输注信息的纸质日志，患者可以在应用程序中记录出血和输注情况。myPKFiT®3.0版本的应用将有助于医患双方加强沟通，通过结合药代动力学特征制定更加优化的个体化治疗方案，进而提升患者的治疗信心，助力改善其生活质量，重获自由人生。杨仁池教授中国医学科学院血液病医院血栓与止血诊疗中心主任随着医学技术的不断革新发展，我国血友病正在迈入更优化、更高效的个体化治疗时代。myPKFiT®3.0版本的上市，将更好地帮助医生‘量体裁衣’，为患者制定更高效的个体化治疗方案，助力更多的A型血友病患者实现‘零出血’的治疗目标，进一步推动我国血友病个体化诊疗发展。单国洪武田制药全球高级副总裁、武田中国总裁非常高兴看到myPKFiT®3.0版本在中国正式获批。作为武田数字化创新的标志性产品，我们期待myPKFiT®3.0版本能够为更多中国A型血友病患者提供定制化的支持，满足其未尽需求；并助力推进A型血友病领域个体化治疗理念的进一步普及。数字化是武田全球的重要战略之一，未来，武田将秉承‘患者为先’的理念，持续引入更多的创新治疗方案，探索数字化科技与医学临床的融合，为更多的中国患者带来健康福祉。审批编号：C-ANPROM/CN/MYPK/0013 审批日期：2024年9月声明 1. 本文所包含的药品信息可能并非在所有国家/地区适用，或在不同的国家/地区可能适用不同的商标、适应症或患者使用剂量。 2. 本文旨在传递医药前沿信息，不构成对任何药物或诊疗方案的推荐或推广。 3. 如您想了解更多疾病知识或药品、诊疗相关信息，请咨询医疗卫生专业人士。注释说明 1.《中国血友病诊治报告2023》 2.《血友病A 诊疗指南（2022 年版）》 3.《血友病治疗中国指南(2020年版)》，中华血液学杂志，2020,41 (2020-04-16). 4. 截止至2024年9月关于武田制药武田制药（东京证券交易所股票代码：4502）（纽约证券交易所股票代码：TAK）是一家总部位于日本、以价值观为基础、以研发为驱动的全球生物制药公司。武田致力于将科学研发成果转化为高度创新药品，为患者的健康生活和美好未来保驾护航。武田专注于四大治疗领域的药物研发：肿瘤、消化、神经科学及罕见病领域，并针对血液制品及疫苗领域进行专项研发投入。我们始终专注于高度创新药物的研发，通过开拓全新治疗方案、增强合作研发引擎实力，打造一条稳健且形式多样的产品管线，助力改善人们的生活。我们的员工遍布于大约80个国家和地区，与当地医疗健康合作伙伴携手，为全球患者带来健康福音。武田于1994年进入中国，武田中国总部位于上海，在中国大陆的主要业务中心位于北京、上海、天津、广州、香港特别行政区等城市和地区，并在全国各主要城市设有办事处，目前在中国拥有超过2000名员工。随着中国经济的发展和对医疗保健需求的不断增长，中国已经成为武田全球最重要的新兴市场之一。更多信息，敬请访问https://www.takeda.com 前瞻性声明本稿件及与之相关的所分发的任何资料可能含有与武田未来业务、未来状况和运营业绩有关的前瞻性陈述、看法或意见，包括武田的预估、预测、目标和计划。前瞻性陈述常常包含但不限于下列措辞，例如“目标”、“计划”、“认为”、“希望”、“继续”、“预计”、“旨在”、“打算”、“确保”、“将”、“可能”、“应”、“会”、“或许”、“预期”、“估计”、“预测”或类似表述或其否定形式。本文中的前瞻性陈述仅基于武田截至发布日期的估计和假设。此类前瞻性声明并非是武田或其管理层对未来业绩所做的任何保证，并涉及已知和未知的风险、不确定性和其他因素，包括但不限于：武田全球业务所面临的经济形势，包括日本和美国的宏观经济环境；竞争压力和发展情况；适用法律法规的变动；产品开发项目的成功或失败；监管当局的决策或做出决策的时机；利率和汇率波动；有关已售产品或候选产品安全或功效的索赔或疑问；已收购公司的合并后整合努力的时机和影响；以及能否剥离对武田运营非核心的资产和任何此类剥离的时机，所有这些都可能会导致武田的实际业绩、表现、成就或财务状况与此类前瞻性陈述所描述或暗指的任何未来业绩、表现、成就或财务状况发生重大偏差。关于以上及可能影响武田结果、业绩、成就或财务状况的其他因素的更多信息，请参阅武田向美国证券交易委员会提交的Form 20-F最新年报“第3项.关键信息—D.风险因素”和其他报告，具体请查阅武田网站https://www.takeda.com/investors/reports/sec-filings/或www.sec.gov。武田的未来结果、业绩成就或财务地位可能与前瞻性陈述所言传或意会的内容有实质性差距。收到这一新闻稿的个人不应对任何前瞻性陈述寄予不适切的依赖。武田没有义务更新本新闻稿中的任何前瞻性陈述或公司可能发布的任何其他前瞻性陈述，除非是法律或证券交易规则所要求。历史业绩并不能代表未来业绩，而且本新闻稿中的武田业绩并不能指代，也并非是武田未来业绩的预估、预测或推测。

免疫疗法上市批准申请上市

2024-01-04

·BioSpace

Be Biopharma Expands Leadership Team as Company Transitions to Clinical Stage Organization

Angus Smith joins as Chief Financial Officer Wing-Yen Wong, M.D., joins as interim Chief Medical Officer CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Be Biopharma, Inc. (“Be Bio”), a company pioneering the development of engineered B Cell Medicines (BCMs), today announced the appointment of Angus Smith as Chief Financial Officer (CFO) and Wing-Yen Wong, M.D., as interim Chief Medical Officer (CMO). Mr. Smith brings more than 15 years of experience in the biotechnology and life sciences industry, having held C-level positions in several public companies, including his most recent role as the CFO of Affimed N.V. and co-President of the company’s U.S. subsidiary, where he was responsible for implementing a new business plan and for raising over $400M in capital to support clinical development efforts. Mr. Smith also brings nearly a decade of investment banking experience, providing strategic and financial advice across the healthcare sector. Dr. Wong brings over 35 years of experience as a practicing clinician and professor at Children’s Hospital of Los Angeles, and leading development efforts in several companies including BioMarin, Biogen, and Baxter. Most recently Dr. Wong was Group Vice-President, Head of Global Medical Affairs and Scientific Strategy at BioMarin where she was involved in the development of the most recently approved hemophilia gene therapy. “We are thrilled to welcome Angus and Wing to Be Bio,” said Joanne Smith-Farrell, Ph.D., Chief Executive Officer. “We are rapidly transitioning from a research-based company to one focused on delivering innovative medicines to patients, with our first program in hemophilia B entering the clinic this year. These accomplished and experienced leaders will further strengthen our leadership team. Angus’s long track record of financial operating experience and fundraising will be important as we advance multiple programs to the clinic, while Wing’s expertise in drug development and as a clinical scientist is particularly important as we pioneer a new class of cellular medicines, Engineered B Cell Medicines (BCMs), to dramatically improve the lives of patients.” Angus Smith Mr. Smith brings more than 15 years of experience in the biotechnology and life sciences industry, including his most recent role as the CFO of Affimed N.V. and, prior to that, at Rockwell Medical. At Affimed, Mr. Smith led all finance, accounting, and investor relations functions, implemented a new business plan and financing strategy, and raised more than $400 million. Mr. Smith began his career in healthcare investment banking, serving most recently as a Director in the Healthcare Investment Banking Group at Cantor Fitzgerald. During his nearly decade-long investment banking tenure, Mr. Smith provided strategic and financial advice to life sciences and healthcare companies. He has worked on a substantial number of transactions across the healthcare sector with an aggregate transaction value of more than $15 billion. Mr. Smith holds a B.A. in Mathematical Economics from Colgate University. Wing-Yen Wong, M.D. Dr. Wong brings over 35 years of experience as a practicing clinician and working in the biotechnology industry with a focus in the treatment and management of patients with hemophilia, sickle cell disease (SCD) and pediatric hematology/oncology. Most recently Dr. Wong was Group Vice-President, Head of Global Medical Affairs and Scientific Strategy at BioMarin and Vice President, Global Medical, Hematology and Immunology at Biogen. Prior to Biogen, Dr. Wong was the Head of Clinical Research and Global Senior Medical Director of Hemophilia/Hematology at Baxter Healthcare Corporation where she directed medical and clinical functions, including global medical support of licensed products, clinical development and new product approvals. During her tenure at Baxter, Dr. Wong successfully directed the BLA submission and launch of multiple hemophilia products including RIXUBIS®, FEIBA®, OBIZUR and ADVATE®. Prior to her work in industry, Dr. Wong spent over 15 years as a practicing clinician and professor at Children’s Hospital Los Angeles and the Los Angeles County (LAC) and University of Southern California (USC) Medical Center. As a clinician, Dr. Wong presented and published numerous studies and papers on her research in hemophilia and hematology and has served as a reviewer for medical journals including the American Journal of Hematology, Hemophilia and the Lancet. In 2003, Dr. Wong was appointed by the Secretary of Health and Human Services as a member of the Advisory Committee on Blood Safety and Availability. Dr. Wong earned her M.D. at the USC, Keck School of Medicine and a BA at Occidental College. She served a Fellowship at the LAC and USC Medical Center in pediatric hematology-oncology and was appointed Associate Professor of Pediatrics at the University of Southern California. About Engineered B Cell Medicines – A New Class of Cellular Medicines The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application – across protein classes, patient populations and therapeutic areas. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page. View source version on businesswire.com: Contacts Investor Contact: ir@be.bio Source: Be Biopharma, Inc. View this news release online at:

高管变更ASH会议细胞疗法

2023-02-01

·医药地理

【好文推荐】凝血因子Ⅷ的长效缓释温敏型水凝胶的研制

未经授权，不得转载凝血因子Ⅷ的长效缓释温敏型水凝胶的研制Preparation of Long-acting Sustained-release Thermosensitive Hydrogels of Coagulation Factor Ⅷ邹茜茜，郜珍叶，张伟捷，吴飞，金拓*(上海交通大学药学院，上海 200240)摘要：凝血因子Ⅷ (F8) 作为治疗血友病常用药物之一，存在半衰期短(10 ～ 14 h) 的缺点，其注射剂需每周多次给药。为获得F8 的长效缓释制剂，该研究通过热开环聚合法得到具反向热敏性质的三嵌段聚合物PLGA-PEG-PLGA 作为温敏水凝胶基质，制备了一种新型长效缓释的温度敏感型水凝胶载F8 制剂，在4 ℃及以下呈溶液，37 ℃附近呈凝胶，并考察了其体外活性及体内外释放行为。结果显示，体外释放试验中，d1 突释了约17.4％的载药量，总共实现了3 周左右的释放，22 d 时F8 的累积释放率达到92％；制剂成胶前后F8 活性达到97％以上，且释放过程中释放液中的F8 活性仍能维持在60％以上，提示温敏水凝胶中的F8 能维持稳定。体内释放曲线表明，大鼠在给药后1 h 达到血药浓度峰值，为(113.21±14.50)ng/ml，整个缓释周期内，血药浓度可维持在最低治疗浓度(10 ng/ml) 以上长达15 d。该研究成功开发了一种F8 长效缓释制剂，具有临床应用潜力。关键词：凝血因子Ⅷ；温敏水凝胶；长效缓释以下为文章节选血友病A 一般是由人体内凝血因子Ⅷ ( factor Ⅷ，F8，1) 缺乏或功能障碍引起的X 连锁出血性疾病。1 由2 332 个氨基酸组成，是相对分子质量高达3×105 的蛋白质，其中的1 条重链和1 条轻链通过金属离子维持非共价键连接[1]。目前对血友病A 患者的主要治疗方法是替代疗法，即静脉注射外源的1 使其达到体内正常水平，而1 往往从人血浆中提取纯化或通过重组DNA 技术生产。当前市场上销售的主流重组凝血1 产品有百特国际(Baxter International) 公司的Advate，德国拜耳(Bayer) 公司生产的三代产品，Kogenate、Kogenate FS 以及Kovaltry。这类重组凝血因子在人体内半衰期只有10 ～ 14 h，因此对预防性治疗的血友病A 患者来说，需要隔天注射或每周静脉注射3 次，以维持至少1％的体内活性。这对需要终身给药的患者来说，生理上异常痛苦且顺应性差。目前已有的延长半衰期的手段包括聚乙二醇修饰(PEGylation)、PEG 化脂质体、生成Fc 融合蛋白等[2—3]。N8-GP( 商品名Esperoct) 由诺和诺德公司生产，于2019 年获得FDA 批准。这是一种基于PEG 修饰原理的长效1 制剂，研究表明在患者中的半衰期延长了1.6 ～ 1.9 倍。DUMONT 等构建了一种重组融合蛋白( rF Ⅷ Fc)，在小鼠和狗的动物模型中，发现rF Ⅷ Fc 的半衰期比rF Ⅷ延长了约2倍[4]。目前的长效缓释研究方法中，1 半衰期至多延长至原来的2 倍，延长更长时间的相关研究几乎是空白的。因此，开发一种新型长效缓释的1 制剂有非常大的临床应用潜力和意义。水凝胶具有独特的三维网格结构，可包载活性成分形成药物贮库，而独特的流变性能也使其具备可注射性，可递送药物到人体或组织内的特定部位，达到缓释效果[5]。大多数化学物质遵循溶解度随温度升高而增加的规律。温度敏感型水凝胶反而是在低温下可溶、在高温成胶，具有反向热敏性质，使其可以在人体皮下原位形成凝胶。另外，通过调节聚合物中亲水与疏水链段的比例可以调节水凝胶的相变温度以及降解速度，从而控制药物的缓释周期，是当前研究较多的一种缓释手段[6]。本研究拟制备出一种可以在37 ℃下原位成胶、缓释长达数周的载1 热敏水凝胶，并考察所得该制剂中的药物活性，以及体内外过程中的药物释放行为。采用三嵌段聚合物，即聚乳酸- 羟基乙酸- 聚乙二醇- 聚乳酸- 羟基乙酸(PLGA-PEG-PLGA) 共聚物(2) 作为热敏水凝胶基质。成胶过程如图1 所示，Tgel 是热敏水凝胶的成胶温度，Tbody 是动物的体内温度；当环境温度低于Tgel 时，体系呈溶液状态，制剂具备可注射性，注射至动物皮下后，由于Tbody 高于Tgel，体系成胶。↑长按二维码阅读全文基金项目：国家自然科学基金项目(81872802)作者简介：邹茜茜(1996—)，女，硕士研究生，专业方向：蛋白药物的长效缓释递送系统研究。通信作者：金拓(1952—)，男，教授，博士，从事生物大分子递药系统的研究。E-mail：tomtjin@gmail.com文章详情欢迎登录《中国医药工业杂志》官网查看。END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

100 项与重组人凝血因子Ⅷ（Takeda）相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	B02BD02	DB00025

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	Baxter Healthcare Corp.	2003-07-25
血友病A	美国	Takeda Pharmaceuticals U.S.A., Inc.	2003-07-25

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
血管性血友病3型	临床3期	美国	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	奥地利	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	比利时	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	捷克	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	法国	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	德国	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	意大利	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	荷兰	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	俄罗斯	Baxalta, Inc.	2017-11-06
血管性血友病3型	临床3期	西班牙	Baxalta, Inc.	2017-11-06

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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


NCT05042440 (Phase 1 sequential pharmacokinetic study, EHA2024) 人工标引	临床1期	血友病A FVIII	13	Octocog alfa	製糧構糧糧築顧糧願鬱(膚製願鑰餘網壓選衊醖) = 繭蓋夢網夢鬱積顧範積觸鑰構鹽簾窪觸淵齋獵 (廠齋鹽壓夢廠選遞選鏇 ) 更多	积极	2024-05-14
	临床1期	血友病A FVIII	13	Rurioctocog alfa pegol	製糧構糧糧築顧糧願鬱(膚製願鑰餘網壓選衊醖) = 製製選選範廠觸餘餘繭觸鑰構鹽簾窪觸淵齋獵 (廠齋鹽壓夢廠選遞選鏇 ) 更多	积极	2024-05-14
NCT04985682 (CTgov)	临床4期	血友病A	50	ADVATE	鑰窪齋製憲鹽製窪鑰蓋 = 廠餘鑰齋鏇選獵窪齋艱壓獵夢鏇夢襯鹹範糧蓋 (憲蓋製襯顧鹹廠築醖蓋, 鬱鹹壓鹹餘顧構遞網餘 ~ 顧鑰糧醖繭願鹽窪襯鏇) 更多	-	2024-03-07
NCT00717626 (CTgov)	临床2期	血友病A	14	Kogenate FS+Advate+Humate-P	憲襯餘鑰鏇壓憲鹽鏇獵(膚廠窪醖膚夢齋糧憲衊) = 構艱淵壓繭築廠遞製網鏇鹹廠艱廠蓋觸憲鑰築 (願積鑰艱鏇淵獵糧夢窪, 範願襯獵淵餘鬱構襯鬱 ~ 窪網齋遞鹽廠積鏇遞鏇) 更多	-	2020-10-08
NCT02306694 (CTgov)	临床3期	血友病A \| 骨病	16	Advate	網簾簾齋願鏇網糧餘築(築鑰願鬱製獵襯齋鏇艱) = 鏇膚獵餘繭餘壓衊膚顧簾鏇鹹簾窪願鹽簾遞簾 (選網鹹製願積鑰觸鏇鏇, 1.22) 更多	-	2020-03-24
NCT01085344 (CHPS, CTgov)	临床4期	血友病A	56	Advate+Recombinant Factor VIII	鏇夢簾獵壓艱鏇艱鹹窪 = 範選壓壓觸蓋鏇遞繭齋糧鹽鬱鹽襯醖衊製選構 (餘醖壓鏇選築齋艱顧鏇, 夢獵網醖範網獵齋鏇廠 ~ 遞鬱積顧艱製築鹽鹹鏇) 更多	-	2019-12-05
NCT00916032 (CTgov)	临床4期	血友病A	29	Advate (One 3000 International Unit (IU) Vial)	鏇製鬱鹽膚廠廠淵鏇夢(願襯獵衊積製選鏇齋衊) = 壓構醖餘繭衊艱構襯艱餘夢壓鑰醖艱艱艱鑰艱 (鏇範鹽餘餘簾選遞簾製, 335) 更多	-	2013-09-05
NCT00916032 (CTgov)	临床4期	血友病A	29	Advate (Two 1500 IU Vials)	鏇製鬱鹽膚廠廠淵鏇夢(願襯獵衊積製選鏇齋衊) = 壓繭製廠襯餘夢齋築願餘夢壓鑰醖艱艱艱鑰艱 (鏇範鹽餘餘簾選遞簾製, 364) 更多	-	2013-09-05
NCT00157157 (Pubmed \| Thromb Haemost)	临床3期	血友病A	55	rAHF-PFM (Advate®)	遞蓋窪鹽壓蓋觸選構積(蓋廠獵憲壓鏇衊窪憲艱) = Related serious adverse events (SAEs) were inhibitor development in 16/55 (29.1%) subjects who received at least one infusion of rAHF-PFM 鏇蓋顧衊鏇鏇網膚鏇網 (齋膚鹽繭醖淵選餘顧糧 ) 更多	-	2012-06-01
NCT00289536 (CTgov)	临床4期	血友病A	38	Antihemophilic factor, recombinant, manufactured protein-free (Low Dose)	餘鏇範鹽膚簾夢壓願繭(艱衊齋艱襯觸築鬱鑰蓋) = 製襯夢鹹簾製願鹹遞願憲築積構網構願獵遞網 (鹹醖顧齋簾繭鹹鏇構窪, 壓糧齋築衊淵齋鏇齋膚 ~ 糧製壓衊蓋夢鹽製鑰窪) 更多	-	2011-01-13
NCT00289536 (CTgov)	临床4期	血友病A	38	Antihemophilic factor, recombinant, manufactured protein-free (Medium Dose)	餘鏇範鹽膚簾夢壓願繭(艱衊齋艱襯觸築鬱鑰蓋) = 構觸鏇繭壓餘築艱鬱繭憲築積構網構願獵遞網 (鹹醖顧齋簾繭鹹鏇構窪, 築齋襯繭選餘鏇夢製積 ~ 選鑰餘鹽艱獵積夢鹹齋) 更多	-	2011-01-13