Adult patients on extracoporeal membrane oxygenation (ECMO) frequently experience bleeding, which is in part caused by acquired von Willebrand syndrome (vWS). Prior in vitro studies have shown that the addition of recombinant von Willebrand Factor (vWF) to ECMO patient blood samples, normalizes platelet adhesion and thrombus formation. This study is a phase I study, where adult ECMO patients with refractory bleeding will be treated with recombinant vWF a single time. The primary objectives are to evaluate the safety, tolerability, and pharmacokinetics of recombinant vWF in adult ECMO patients.

开始日期2024-08-01

申办/合作机构

University of Virginia

NCT03879135 / Recruiting临床3期

A Phase 3b, Prospective, Open-Label, Uncontrolled, Multicenter Study on Long-Term Safety and Efficacy of rVWF in Pediatric and Adult Subjects With Severe Von Willebrand Disease (VWD)

The main aim of the study is to check effectiveness of rVWF (vonicog alfa) prophylaxis based on the annualized bleeding rate (ABR) of spontaneous (not related to trauma) bleeding episodes in pediatric and adult participants during the first 12 months on study treatment.
The participants will be treated with rVWF for a maximum of 3 years. Their von Willebrand Disease will be treated according to Investigational product (IP) dosing directions.

开始日期2019-04-01

申办/合作机构

Baxalta, Inc.

[+1]

NCT02932618 / Recruiting临床3期

A Phase 3, Prospective, Multicenter, Uncontrolled, Open-Label Clinical Study to Determine the Efficacy, Safety, and Tolerability of rVWF With or Without ADVATE in the Treatment and Control of Bleeding Episodes, the Efficacy and Safety of rVWF in Elective and Emergency Surgeries, and the Pharmacokinetics (PK) of rVWF in Children Diagnosed With Severe Von Willebrand Disease

The main aim of the study is to check effectiveness, side effects, and tolerability of recombinant von Willebrand Factor (rVWF), with or without ADVATE, in the treatment and control of nonsurgical bleeding events in pediatric participants (less than (<)18 years of age) with severe hereditary von Willebrand disease (VWD).
The participants will be treated with rVWF for 12-18 months. Their von Willebrand Disease will be treated by their doctor according to their doctor's usual clinical practice. During the study, participants will be followed up at clinics or over telephone calls.

开始日期2017-12-18

申办/合作机构

Baxalta, Inc.

[+1]

100 项与 Vonicog Alfa (Baxalta) 相关的临床结果

登录后查看更多信息

100 项与 Vonicog Alfa (Baxalta) 相关的转化医学

登录后查看更多信息

100 项与 Vonicog Alfa (Baxalta) 相关的专利（医药）

登录后查看更多信息

366

项与 Vonicog Alfa (Baxalta) 相关的文献（医药）

2024-01-01·Annals of plastic surgery

Abdominoplasty in a Patient With Type 3 von Willebrand Disease

Article

作者: Kessler, Katharina ; Kuhlmann, Constanze ; Mert, Sinan ; Wiggenhauser, Paul S ; Hagen, Christine Sophie ; Giunta, Riccardo E ; Balubaid, Mohammed

Abstract:

von Willebrand disease (vWD) is an inherited bleeding disorder that is characterized by a quantitative or qualitative deficiency of the von Willebrand factor (vWF). Type 3 is the most severe form of vWD with a near-complete absence of vWF and a significantly increased risk of excessive bleeding and hematoma during a surgical procedure. To date, no data on surgical and hemostatic management of a type 3 vWD patient undergoing body-contouring surgery has been published. We report the case of a 47-year-old woman with type 3 vWD requiring medically indicated abdominoplasty after massive weight loss due to bariatric surgery. The case was successfully managed with individualized bodyweight-adapted substitution of recombinant vWF vonicog alfa and tranexamic acid under close monitoring of vWF and factor VIII activity. For further risk stratification, we propose the multidisciplinary treatment of patients with severe vWF undergoing elective plastic surgery in specialized centers providing around-the-clock laboratory testing and access to a blood bank. In addition, strict hemostasis during surgery and early postoperative mobilization with fitted compression garments are recommended to further reduce the risk of bleeding and thromboembolic complications.

2024-01-01·Haemophilia : the official journal of the World Federation of Hemophilia

Safety, pharmacokinetics and efficacy of a subcutaneous recombinant FVIII (OCTA101) in adult patients with severe haemophilia A

Article

作者: Jansen, Martina ; Bichler, Johann ; Lissitchkov, Toshko ; Knaub, Sigurd

Abstract:

Introduction:

Regular, prophylactic intravenous (i.v.) FVIII can be challenging for some patients with haemophilia A. Subcutaneous (s.c.) FVIII administration could provide an alternative treatment option with greater convenience and without the complications associated with venous access.

Aim:

To assess the safety, pharmacokinetics (PK), bioavailability and efficacy of s.c. OCTA101, a recombinant FVIII with a recombinant von Willebrand factor fragment dimer.

Methods:

This was a single‐centre, prospective, open‐label, phase I/II study (NCT04046848). Previously treated male patients (≥18 years) with severe haemophilia A were eligible for the study. The primary objective of the study was to assess the safety (including immunogenicity) of OCTA101. Secondary objectives included assessments of PK, bioavailability, and the efficacy of prophylaxis.

Results:

Thirty patients were treated with OCTA101. FVIII inhibitors developed in five (16.7%) patients during daily prophylaxis with 40–60 IU/kg (three cases) and 12.5 IU/kg (two cases) OCTA101. The trial was therefore terminated. OCTA101 had a 2.5‐fold longer terminal half‐life compared with i.v. rFVIII, and bioavailability was 16.6%. Efficacy data at study termination indicated that daily prophylaxis with 40–60 IU/kg OCTA101 was efficacious in the absence of FVIII inhibitors.

Conclusions:

Despite promising PK and efficacy results, the trial was terminated due to the incidence of FVIII inhibitors. The occurrence of inhibitors at two dose levels suggests that their development may be related to the subcutaneous route of administration.

2024-01-01·Haemophilia : the official journal of the World Federation of Hemophilia

In vitro field study and worldwide survey assessing how clinical haemostasis laboratories analyse recombinant and plasma‐derived von Willebrand factor products

Article

作者: Gritsch, Herbert ; Ilk, Reinhard ; Turecek, Peter L

Abstract:

Introduction:

Several well‐established clinical laboratory methods are available to measure von Willebrand factor (VWF) in plasma samples, but few data are available on their use for analysing recombinant VWF (rVWF).

Aim:

To evaluate how clinical diagnostic laboratories analyse rVWF and plasma‐derived VWF (pdVWF) spiked in vitro into VWF‐deficient plasma using quantitative protein and functional assays of VWF.

Methods:

Human VWF‐deficient plasma samples were spiked with rVWF (vonicog alfa; Takeda) or pdVWF/factor VIII (pdVWF/FVIII; antihemophilic factor/VWF complex [human], CSL Behring), each at final concentrations of 1.0, 0.6, 0.2, 0.1 IU/mL VWF:ristocetin cofactor activity (VWF:RCo) according to labelled VWF activity. The ISTH SSC secondary coagulation standard was used as a control. Participating laboratories received three sets of these blinded aliquots. Mean results per assay were compared with the expected potency based on the labelled VWF:RCo activity.

Results:

Among 39 laboratories, the most commonly established assay was VWF:RCo; 22 laboratories reported data from 2214 tests. Despite a trend to lower values, VWF:RCo activities for rVWF were in agreement with target concentrations (71%–109%), whereas VWF:platelet glycoprotein Ib (VWF:GpIb) and VWF collagen‐binding activity (VWF:CB) assays gave high recoveries (up to 132% and 127%, respectively). In contrast, pdVWF/FVIII was substantially underestimated by VWF:GpIb and VWF:CB assays (56%–86% recoveries), whereas the VWF:RCo assay gave recoveries of 47%–112% for pdVWF/FVIII.

Conclusion:

The results of VWF assays used in clinical laboratories differ between rVWF and pdVWF, particularly for VWF:GpIb and VWF:CB assays. These differences may arise from the higher multimeric structure of rVWF compared to pdVWF.

项与 Vonicog Alfa (Baxalta) 相关的新闻（医药）

2024-01-11

·生物制品圈

通过连续、集成的下游工艺，强化重组凝血因子捕获操作

本文节选自来自Takeda等的研究人员发表的文章“Intensified capture of recombinant blood coagulation factors by continuous, integrated downstream processing”，详细内容，请参考原文。背景：生物制药界已经意识到连续工艺在工艺强化方面的巨大潜力。然而，迄今为止，单克隆抗体 (mAb) 连续工艺的报告占绝大多数，而非 mAb 产品的集成连续工艺却很少。结果：我们开发了一种集成、连续的工艺来捕获重组凝血因子：因子 VIII (FVIII) 和 VonWillebrand 因子 (VWF)。由于其复杂性和多样性，连续生产非单克隆抗体产品需要层析分离之外的定制解决方案。我们的集成工艺由三个连续单元操作组成，包括细胞去除、通过沉淀捕获产物以及沉淀物收集，FVIII 和 VWF 的收率分别为 33% 和 56%。这些单元操作是单独开发的，然后集成到实验室规模的连续工艺中。使用原型设备，我们证实了在 24 小时内连续、集成捕获重组凝血因子的策略。结论：所采用的连续解决方案是针对 FVIII 和 VWF 开发的，但很可能适用于其它分子。这些连续固液分离和集成的解决方案是生物制药连续下游工艺难题的重要组成部分。简介几种重组凝血因子在连续搅拌罐反应器 (CSTR) 中连续生产，但下游工艺仍以批次模式进行。基因治疗或双特异性抗体等下一代生物制药的引入导致市场压力越来越大。因此，传统生物药的制造商正在寻求集成的连续生物生产来减轻这种压力。因此，灌流培养和逆流层析等连续工艺技术重新受到关注。过去，连续上游生产主要用于去除生物反应器中的副产物或不稳定产物，例如凝血因子或酶。在这些情况下，连续上游工艺经常与批次下游工艺相结合。然而，连续工艺的真正潜力只能体现在可用于完全集成的端到端连续（生物）工艺。端到端连续工艺需要使所有单元操作适应连续操作。对于由层析分离和基于过滤的步骤组成的单克隆抗体 (mAb) 平台工艺，已报道了中试和实验室规模的工艺。此外，连续生产对单克隆抗体生产工艺成本结构的影响已得到详细评估，也可作为将其它产品类别的批次工艺转为连续工艺的激励措施。多样性和非 mAb 产品（例如重组凝血因子）的特殊性需要采用超出连续（Protein A）层析法的定制方法进行纯化。可用于连续工艺的非层析技术包括水相两相萃取 (ATPE) 和沉淀。这些单元操作的优点是可随体积线性放大，同时很大程度上与浓度无关。此类单元的材料成本操作成本较低，因为 PEG 和无机盐等沉淀剂比典型的层析填料便宜。此外，ATPE 和沉淀是基于流动的技术，仅需要连续混合、孵育和分离的技术解决方案。然而，连续固体–液体分离已被确定为连续下游工艺的瓶颈。沉淀物在固液分离过程中所经历的压实程度对给定沉淀物的再溶解效率有显著影响。增加压实破坏了天然絮凝体结构，并对再溶解带来了额外的挑战。对于连续固液分离，已经提出了许多解决方案。这些包括切向流过滤、流化床离心、水力旋流器和重力分离，每一种都有其优点和缺点。合适的固液分离解决方案的可用性对于连续沉淀的整体可行性至关重要。由于其基于流动的性质，连续沉淀非常适合直接集成和强化生产工艺，并减少处理时间。预计这种处理时间的缩短将特别有利于复杂的分子，例如分子。重组凝血因子。本文报道的工作目标是建立生产重组凝血因子 VIII (FVIII) 和 VonWillebrand 因子 (VWF) 的连续下游工艺。目前，这些分子是在连续的上游工艺中生产的，但以批次模式纯化。我们报告了一个持续、集成的工艺流程，并在实验室规模进行了概念验证。10 L 小规模生物反应器成功地与倾斜沉降器相结合，以连续去除细胞。通过磷酸钙沉淀从澄清的细胞培养上清液（CCCSN）中连续并同时捕获FVIII和VWF，并将含有产物的沉淀物收集在第二个倾斜沉降器中。因此，我们证明了低成本、简单且稳健的连续集成下游工艺的可行性，并且可以根据需要进行扩展。详细的试验操作和结果分析，请参考原文。在实验室规模实现的连续工艺的示意图。BR = 生物反应器，Px = 泵号x，Sx = 采样点号x、B-T = 气泡捕捉器、T-I = 浊度指示器、Temp-I = 温度指示器、TR = 管式反应器、pH-I = pH指示器、pH-C = pH控制器、Level-x = 液位控制刻度x，prec. = 沉淀。流动方向是从左到右。该过程在 2–8°C 下进行。23小时以上连续沉降过程数据。使用自动设置进行 CCCSN 沉淀。使用不同组成的洗涤液获得的 FVIII 和 VWF 的归一化产率。将结果标准化为未洗涤的样品，其以与其它样品相同的方式沉降。误差线代表三个物理重复的 SD。在 40 mL/min、30min 排液间隔、不同排液持续时间或体积下获得的排液峰。累计排出量为(A) 45mL、(B)22.5mL、(C)12.8mL。(D) 不同排放量的排放部分中发现的示踪剂的产率和浓度。讨论我们报道了用于捕获重组凝血因子的连续、集成工艺的开发。第一个工艺步骤是连续细胞去除步骤，该步骤是使用具有结构化设计底部的倾斜沉降器实现的。在实验室规模下使用倾斜沉降器进行连续细胞去除是简单而稳健的。与交替式切向流过滤（ATF）或离心法中报告的过滤器损失相比，不到 3.5% 的产物损失要小得多。由于低剪切环境且不存在任何可能导致产物流失的物理屏障，倾斜沉降器非常适合大尺寸、高度复杂的蛋白质，例如 rFVIII 和 rVWF。由于澄清流体的连续流动，与后续单元操作的集成预计会很简单。我们证明使用磷酸钙连续沉淀 FVIII:VWF 复合物是可行的。我们现在已经以连续的方式进行了这种沉淀，这是使用简单的实验室规模设备与定制软件工具相结合来实现的。该过程可使用基本反馈控制进行控制，可直接应用于生产规模。虽然技术实现和工艺稳定性结果非常有希望，但第一批产品的收率结果仍然不令人满意。因此，对沉淀工艺进行了两处修改：首先，将复溶剂从柠檬酸盐改为EDTA；其次，沉淀前的pH设定点从8.5增加到8.75。通过这两项改变，批次模式下的产物收率可以达到>94%。当使用改进的条件进行连续沉淀时，FVIII 和 VWF 的最终收率分别为 74% 和 82%。这些数字意味着 FVIII 的产物收率增加了 18%，VWF 的产物收率减少了 3%（结果总结于表 4）。有趣的是，批次操作和连续操作之间的收率差异无法消除。表 4. 整个过程中产物收率和体积减少系数汇总我们认为这些差异是由于操作模式本身造成的。与连续沉淀或逐步添加相比，批次沉淀通常会产生不同的絮凝体尺寸分布。在批次模式中，单次添加沉淀剂会产生一定数量的核，并且它们将继续生长。在 CSTR 中，当处于稳态时，存在核，并且形成新的核并被洗掉。除了操作模式的影响之外，我们的结果表明沉淀后的 pH 值（尤其是复溶后的 pH 值）对于 FVIII 收率至关重要。对于试验或生产过程，需要密切控制这些过程参数。更严格的 pH 控制可以通过额外的反馈控制或前馈控制回路来实现。汇总表还显示了假设改进的沉淀物收集后的收率。基于改进的连续沉淀收率，我们预计改进的沉淀物收集工艺的收率将大于 51%，因为前面的沉淀步骤有所增加。沉淀物收集本身的收率可以通过改变洗涤流体成分来提高。此处，仅优化了沉淀物收集中使用的洗涤液的钙浓度。其它因素，例如溶液 pH 值和额外的补充剂，如表面活性剂，可能会提高产物在洗涤液中的稳定性。根据后续单元操作（可能是层析步骤、超滤/洗滤或病毒灭活）的性质和要求，可以调整洗涤液成分，以促进工艺集成。就预期产量而言，我们的工艺在性能上与文献中报道的其它工艺相当。据报道，在使用凝集素的亲和层析的早期研究中，FVIII 和 VWF 的总产率为 40-57%。最近使用离子交换层析的文献报告 FVIII 的收率为 40-80%。通过应用逆流上样，交换层析也转变为连续操作。层析分离获得的最佳结果是与 VWF 共纯化的 FVIII 的回收率 > 86%，其中特异性活性至少为 140 IU/mg−1。但必须谨慎解释收率数据，因为起始材料的质量会影响最终收率。由于血浆是一种珍贵材料，实验室规模实验通常使用较为劣质的材料进行。总结该工艺代表了重组蛋白强化下游工艺的一个典型例子。通过采用稳健、易于控制的设备，我们在实验室规模上建立了一个集成的、连续的工艺流程，并以全自动方式运行。虽然这个特定工艺有改进的潜力，但结果凸显了连续工艺的关键特征之一，即加深对工艺的理解。我们的结论是，有可能建立一个集成的、连续的生物生产工艺来生产 FVIII:VWF 复合物。该工艺是在 10L 生物反应器规模下进行的，因此我们假设这样的工艺过程也是可放大的。该工艺的设计也是为了建立一个功能封闭的系统。原文：H.Engelmaier, C.Dattenbock, K.Petrushevska-Seebach, et al., Intensified capture of recombinant blood coagulation factors by continuous, integrated downstream processing. Journal of Chemical Technology and Biotechnology, 2023.识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

基因疗法

2023-12-05

·PRNewswire

Octapharma USA: FDA Grants Expanded Approval to wilate® as the First VWF Concentrate for Prophylaxis in All Types of VWD

Routine Prophylaxis Now Recommended for Adults and Children Aged 6 and Older with Severe VWD PARAMUS, N.J., Dec. 5, 2023 /PRNewswire/ -- Octapharma USA announced the expansion of the U.S. Food and Drug Administration (FDA) approval for wilate®, von Willebrand Factor/Coagulation Factor VIII Complex (Human) Lyophilized Powder for Solution for Intravenous Injection. The approved label now includes routine prophylaxis aimed at reducing the frequency of bleeding episodes in adults and children aged 6 and older with any type of von Willebrand disease (VWD), the most prevalent bleeding disorder in the United States. Wilate® is the first von Willebrand factor (VWF) concentrate indicated for prophylactic treatment across all forms of VWD, marking a significant milestone in the field. Continue Reading Octapharma USA: FDA Grants Expanded Approval to wilate® as the First VWF Concentrate for Prophylaxis in All Types of VWD Post this Octapharma USA announced the expansion of the U.S. Food and Drug Administration approval for wilate®, von Willebrand Factor/Coagulation Factor VIII Complex (Human) Lyophilized Powder for Solution for Intravenous Injection. The approved label now includes routine prophylaxis aimed at reducing the frequency of bleeding episodes in adults and children aged 6 and older with any type of von Willebrand disease (VWD), the most prevalent bleeding disorder in the United States. "Long-term prophylaxis with VWF concentrate, as compared to on-demand treatment for bleeding, is recommended for patients with severe VWD," according to Shveta Gupta, MD, a specialist in pediatric hematology and oncology with The Haley Center for Children's Cancer and Blood Disorders at Orlando Health Arnold Palmer Hospital for Children. "The approval of wilate® for VWD prophylaxis is a welcome new treatment option that can be life-saving for many patients. Increased use of VWF prophylaxis in VWD patients may lead to improved patient care and a reduced burden of disease." WIL-31 Study: A Breakthrough in VWD Treatment The FDA approval is supported by Octapharma's WIL-31 study, a prospective, non-controlled, international, multicenter phase 3 trial that investigated the efficacy and safety of wilate® prophylaxis over 12 months in people aged 6 and older with severe VWD of any type. All WIL-31 patients received on-demand treatment with wilate® during a previous six-month, prospective, observational study (WIL-29). Patients who experienced at least six bleeding episodes (BEs), excluding menstrual bleeds, with at least two of these BEs treated with a VWF-containing product, were eligible to enter WIL-31. Patients in WIL-31 received wilate® prophylaxis two to three times per week at a dose of 20-40 IU/kg, for 12 months. The clinical trial's primary purpose was to investigate whether prophylaxis with wilate® lowered the mean total annualized bleeding rate (ABR) by more than 50% compared to the six months of on-demand treatment. Secondary goals were to measure spontaneous ABR and treatment-emergent adverse events.1 Researchers reported an 84% reduction in the mean total ABR compared with on-demand treatment during the prior study. The median spontaneous ABR decreased by 95%. Importantly, no serious drug-related adverse events or thrombotic events were observed during the study. Addressing the Prevalence of VWD in the U.S. Population Von Willebrand disease affects up to 1% of the U.S. population, equating to about 3.3 million individuals. The disease, occurring equally among men and women, is often noticed more by women due to heavy or abnormal bleeding during menstrual periods and after childbirth. VWD includes three major types – Type 1, Type 2, and Type 3, the most severe form. The expanded wilate® label provides a treatment option for a significant patient population.2 "Wilate® prophylaxis for adults and children aged 6 and older with VWD promises to be life-changing for many patients," stated Octapharma USA President Flemming Nielsen. "Patients have been forced to live with far too many bleeding episodes while receiving on-demand treatment. Octapharma is pleased to offer patients a new therapy option that can greatly improve their quality of life." Factor My Way: Empowering VWD Patients In tandem with this approval, Octapharma USA extends its commitment to patient care through the Factor My Way patient support program. Tailored for those living with VWD and hemophilia A, this free membership program provides access to caregivers, educational programs, a resource library, and more. For additional information, please visit FactorMyWay.com. About wilate ® Wilate®, von Willebrand Factor/Coagulation Factor VIII Complex (Human) Lyophilized Powder for Solution for Intravenous Injection is indicated in children and adults with von Willebrand disease for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Wilate® is indicated for routine prophylaxis in children 6 years of age and older and adults with von Willebrand disease. Wilate® is indicated in adolescents and adults with hemophilia A for: Routine prophylaxis to reduce the frequency of bleeding episodes On-demand treatment and control of bleeding episodes CONTRAINDICATIONS Do not use in patients with known hypersensitivity reactions, including anaphylactic or severe systemic reaction, to human plasma-derived products, any ingredient in the formulation, or components of the container. WARNINGS AND PRECAUTIONS Anaphylaxis and severe hypersensitivity reactions are possible. Thromboembolic events may occur. Monitor plasma levels of FVIII activity. Development of neutralizing antibodies to FVIII and to VWF, especially in VWD type 3 patients, may occur. Wilate® is made from human plasma and carries the risk of transmitting infectious agents. For complete prescribing information, please visit wilateusa.com/pi. About the Octapharma Group Headquartered in Lachen, Switzerland, Octapharma is one of the largest human protein manufacturers in the world, developing and producing human proteins from human plasma and human cell lines. Octapharma employs more than 11,000 people worldwide to support the treatment of patients in 118 countries with products across three therapeutic areas: Hematology, Immunotherapy and Critical Care. Octapharma has seven R&D sites and five state-of-the-art manufacturing facilities in Austria, France, Germany and Sweden, and operates more than 190 plasma donation centers across Europe and the US. The company's American subsidiary, Octapharma USA, is located in Paramus, N.J. For more information, please visit octapharmausa.com. REFERENCES 1 – Robert F. Sidonio, Jr., Ana Boban, Leonid Dubey, Adlette Inati, Csongor Kiss, Toshko Lissitchkov, Dzmitry Novik, Elina Peteva, Ali T. Taher, Margarita Arkadevna Timofeeva, Kateryna V. Vilchevska, Vladimir Vdovin, Sylvia Werner, Sigurd Knaub, Claudia Khayat; Efficacy and Safety of Prophylaxis with a Plasma-Derived Von Willebrand Factor/ Factor VIII Concentrate in Previously Treated Patients with Von Willebrand Disease. Blood 2022; 140 (Supplement 1): 8438–8439. doi: . 2 – Centers for Disease Control and Prevention, What is von Willebrand Disease. SOURCE Octapharma

临床结果上市批准临床3期

2023-11-02

·研发客

携手本土创新企业武田在血友病领域再下一城 | 第一现场

// 针对血友病的基因治疗，是武田在该疾病领域中的又一块重要的拼图。越来越频繁的授权交易，预示着跨国药企与中国新药公司之间的合作已逐渐进入深水区。一周前，BMS宣布与联拓生物达成一项治疗肥厚型心肌病药物的交易。实际上，今年以来，AZ、GSK 、强生、罗氏等多家跨国药企纷纷与中国新药公司开展合作。随着一批本土创新企业的崛起与成熟，跨国药企看到了扎根中国，乃至领跑全球的新机遇。作为罕见病领域的全球领先者，武田制药也一直在积极寻找中国的合作伙伴。最近，武田中国与本土创新型企业信念医药（Belief BioMed，BBM）达成合作协议，信念医药授权武田中国负责治疗B型血友病的创新基因疗法BBM-H901注射液在中国大陆、中国香港和中国澳门的商业化。根据协议，武田将负责该产品在中国的市场策略、销售策略以及医学事务等方面的商业化工作。基因疗法罕见病患者的新希望对于普通人来说，罕见病可能只是某部影视作品中的一颗催泪弹，但对于全球3亿的罕见病患者而言，疾病的痛苦与负担终身相伴。正因如此，罕见病领域的创新疗法一直被寄予厚望。2018年，第一款RNAi疗法上市，让该疗法在罕见病领域的治疗备受期待。就在今年9月，FDA批准了一款RNAi疗法，用于治疗9岁及以上儿童和成人1型原发性高草酸尿症(PH1)。基因治疗是罕见病患者的另一道曙光。近年来，罕见病基因治疗的研发热度持续攀升，2022年，FDA共批准了3款治疗罕见病的基因疗法。分别用于治疗β-地中海贫血、肾上腺脑白质营养不良和血友病。值得关注的是，全球范围内，针对血友病基因疗法的研发，正在开启该疾病领域的新篇章。血友病作为一种遗传性凝血功能障碍疾病，分为A和B两种亚型。其中B型血友病是由于血液中缺乏凝血因子Ⅸ(FIX)所致，患者绝大部分为男性，其特点为反复的、自发性的关节、肌肉和软组织出血，如长时间反复出血，还可能导致患者关节畸形、肌肉萎缩甚至死亡。目前，预防和按需使用凝血因子替代疗法是血友病的标准治疗方案。尽管这种治疗方式可以让疾病得到一定程度的缓解，但终身反复注射，不仅严重影响患者的生活质量，也带来了巨大的治疗负担。随着基因疗法的不断成熟，血友病患者看到了新的希望。与传统治疗方式相比，理论上，基因治疗药物具有“一次给药，长期有效”的优势，可以让血友病患者体内凝血因子水平长期维持在临床治愈水平，同时能减少注射次数以及规避使用血液产品带来的感染风险。加快落地让更多中国患者获益此次武田中国与信念医药达成授权合作的BBM-H901注射液，是一款由信念医药自主研发的腺相关病毒（AAV）基因治疗药物，也是国内第一个获批进入注册临床试验的、治疗B型血友病的AAV基因治疗药物，于2022年先后登上国际权威期刊《柳叶刀-血液病学》和《新英格兰医学杂志》，已被国家药监局药品审评中心纳入“突破性治疗品种”名单。已发表临床研究数据显示，BBM-H901注射液具有良好的安全性和有效性，AAV基因治疗药物输注后患者体内凝血因子水平提高显著，并长期稳定，且在临床期间未发现明显的不良反应，患者的年化出血率（ABR）显著降低。《柳叶刀-血液病学》曾刊登的临床研究结果表明，18岁以上、FIX残留水平≤2IU/ dl的血友病B患者接受BBM-H901注射液治疗后，中位58周随访显示出“3个0”的临床获益：患者中位年化出血率从12次减少至0次，中位靶关节数从1.5个减少至0个，中位凝血因子IX药物年输注次数从53.5次减少至0次。据统计，目前我国注册登记的B型血友病患者约3800人，这些患者仍然背负着沉重的治疗负担和长久的疾病困扰。中国在B型血友病领域的治疗仍有着未被满足的需求。显然，此番武田中国与信念医药的合作，有望加速基因疗法在中国的落地，帮助更多患者回归正常生活。武田中国表示，公司商业化方面有非常成熟的经验，一旦药物获得国家药品监督管理局（NMPA）批准，将利用自身在罕见病领域的商业化规模和专业知识，将该创新疗法带给中国患者。同时，双方将结合各自优势和资源，推动B型血友病基因疗法在中国的普及，帮助更多B型血友病患者长期获益于领先的基因疗法，提升罕见病创新药的可及性。拓展产品组合持续深耕中国作为全球罕见病领域的代表性企业，多年来，武田加速推动了多款罕见病创新药物进入中国。包括治疗I型戈谢病的维葡瑞、全球首个针对遗传性血管性水肿（HAE）预防治疗的达泽优和用于治疗急性发作的飞泽优、治疗法布雷病的瑞普佳等。血友病是武田在罕见血液疾病领域的重要组成部分，公司持续引入先进预防性治疗与个体化治疗方案，包括用于血友病预防治疗的百因止（基因重组凝血因子Ⅷ）、血友病个体化治疗管理软件myPKFiT。此外，用于治疗获得性血友病A的Obizur和治疗血管性血友病的Vonvendi也已在中国递交上市申请。而针对血友病的基因治疗，可以说是武田在该疾病领域中的又一块重要的拼图。与信念医药的合作，将进一步丰富武田在罕见病领域的产品组合，也让其在罕见病创新疗法上的突破，站上了新的高度。武田相信，其在罕见病领域的专业知识和丰富经验，将能助力中国本土创新的开花结果，同时也将在未来推动更多创新方案在中国落地，为中国的创新市场注入更多活力，最终在实现患者获益，也为“健康中国2030”贡献武田力量。编辑 | 姚嘉yao.jia@PharmaDJ.com 总第1990期访问研发客网站可浏览更多文章www.PharmaDJ.com

基因疗法上市批准核酸药物

100 项与 Vonicog Alfa (Baxalta) 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D08681	Vonicog Alfa (Baxalta)	B02BD10	DB12872

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
冯·维勒布兰德病	欧盟	Baxalta Innovations GmbH	2018-08-31
冯·维勒布兰德病	冰岛	Baxalta Innovations GmbH	2018-08-31
冯·维勒布兰德病	列支敦士登	Baxalta Innovations GmbH	2018-08-31
冯·维勒布兰德病	挪威	Baxalta Innovations GmbH	2018-08-31
血管性血友病3型	美国	Takeda Pharmaceuticals U.S.A., Inc.	2015-12-08

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
出血	临床3期	美国	Baxalta, Inc.	2011-11-01
出血	临床3期	日本	Baxalta, Inc.	2011-11-01
出血	临床3期	澳大利亚	Baxalta, Inc.	2011-11-01
出血	临床3期	奥地利	Baxalta, Inc.	2011-11-01
出血	临床3期	比利时	Baxalta, Inc.	2011-11-01
出血	临床3期	保加利亚	Baxalta, Inc.	2011-11-01
出血	临床3期	加拿大	Baxalta, Inc.	2011-11-01
出血	临床3期	德国	Baxalta, Inc.	2011-11-01
出血	临床3期	印度	Baxalta, Inc.	2011-11-01
出血	临床3期	意大利	Baxalta, Inc.	2011-11-01

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	冯·维勒布兰德病	82	Recombinant von Willebrand factor (rVWF)	製鏇膚憲網艱積糧夢觸(窪鹽簾簾襯艱衊醖構糧) = 醖觸鹹繭夢艱憲顧製選齋觸襯糧糧鏇鑰選餘範 (廠淵簾鬱鹹遞選艱鏇窪 )	-	2023-06-24
EASL2023	N/A	肝细胞癌	443	von Willebrand factor antigen (Low-risk group)	顧鏇淵鬱製鬱製蓋網遞(製醖構齋鑰夢簾繭襯廠) = 選衊範鏇夢襯觸顧艱鬱艱鹹糧顧獵鏇築淵襯艱 (築獵鑰鏇淵築簾獵獵觸 ) 更多	-	2023-06-21
				von Willebrand factor antigen (Intermediate-risk group)	顧鏇淵鬱製鬱製蓋網遞(製醖構齋鑰夢簾繭襯廠) = 蓋齋鑰蓋糧窪築製簾獵艱鹹糧顧獵鏇築淵襯艱 (築獵鑰鏇淵築簾獵獵觸 ) 更多
ISTH2022	N/A	2型血管性血友病	-	Recombinant VWF concentrate	築鏇鹽淵醖繭夢衊範鬱(簾衊製淵獵鹽齋選鹹壓) = 築網鏇糧鹽壓糧繭廠膚襯餘鏇廠顧遞網網遞廠 (鏇廠襯醖觸築網觸膚獵 ) 更多	-	2022-07-09
NCT02973087 (Pubmed \| Blood) 人工标引	临床3期	冯·维勒布兰德病	23	Recombinant von Willebrand factor (Prior On-Demand group)	網憲鬱鏇築網製簾構鑰(選齋築觸蓋膚積遞餘鏇) = 簾壓鹽製選窪蓋構廠艱廠範廠壓繭鹹艱簾蓋艱 (蓋選蓋構膚憲繭憲觸願 )	积极	2022-04-19
				Recombinant von Willebrand factor (Switch group)	網憲鬱鏇築網製簾構鑰(選齋築觸蓋膚積遞餘鏇) = 構窪鬱淵鏇積範獵醖壓廠範廠壓繭鹹艱簾蓋艱 (蓋選蓋構膚憲繭憲觸願 )
NCT02973087 (CTgov)	临床3期	冯·维勒布兰德病	29	VWF concentrate+rVWF (Prior On-demand Participants)	觸餘艱壓餘構鹹鏇築餘(獵淵觸製鬱網鑰衊淵衊) = 襯鹽鹹遞選製廠淵壓選鏇膚鏇鹽顧壓繭繭構艱 (襯艱構鏇蓋築網簾網繭, 繭壓糧簾夢積糧醖壓築 ~ 艱築窪壓構構淵糧壓蓋) 更多	-	2021-08-06
				VWF concentrate+rVWF (Switch Participants)	觸餘艱壓餘構鹹鏇築餘(獵淵觸製鬱網鑰衊淵衊) = 膚積齋範襯遞遞憲製襯鏇膚鏇鹽顧壓繭繭構艱 (襯艱構鏇蓋築網簾網繭, 餘壓築鬱築憲齋簾製鹹 ~ 壓製遞願艱憲獵範鏇繭) 更多
ISTH2021	N/A	乳腺癌 Von Willebrand Factor	-	Von Willebrand Factor	夢艱鹹憲網獵壓網鬱鑰(願糧網窪餘淵艱鹽獵襯) = 餘餘範觸鹽衊築鑰膚選憲憲膚築鬱築觸衊鬱鑰 (齋顧窪衊憲網鑰觸繭窪 )	-	2021-07-17
				Von Willebrand Factor	糧選鹽夢鏇鹹憲鏇艱繭(蓋夢鹽製選築膚網鬱窪) = 鹽鑰築鹽顧製壓餘廠夢獵膚遞範窪鏇製觸蓋壓 (齋範簾簾製醖艱醖網鹹 ) 更多
MO763 (ERA2021)	N/A	动静脉瘘 von Willebrand Factor (VWF)	-	Von Willebrand factor	鬱顧製衊構繭顧鑰憲廠(顧鹽膚繭繭顧顧範網廠) = 網齋襯艱鏇網願鬱艱餘鑰繭襯壓構壓鹽顧願鹽 (憲鹹衊積構鏇選獵鹽廠 )	积极	2021-05-29
				Von Willebrand factor	鏇糧廠夢顧繭構鑰夢獵(鏇獵鬱築淵獵窪鬱鏇蓋) = 繭餘築襯獵鏇餘簾壓顧廠夢鏇鏇夢憲製顧窪鹹 (齋遞繭餘餘衊網構鹹積 ) 更多
ISC2021	N/A	脑卒中	-	Von Willebrand Factor (VWF) (ipsilateral LMCs)	築顧獵壓醖淵蓋製遞遞(艱願壓製醖遞膚繭築廠) = 糧餘襯衊鏇簾糧艱餘鑰壓簾選選齋鬱鏇鬱艱觸 (夢製選艱窪糧觸鑰鏇鹽 ) 更多	-	2021-03-01
				Von Willebrand Factor (VWF) (contralateral LMCs)	憲齋鬱積鹹鹽鏇選網餘(餘網鏇遞廠襯夢獵簾蓋) = 顧餘製鹹齋繭製廠夢壓憲艱獵夢膚蓋網壓醖獵 (淵餘簾壓鏇餘簾鏇築築 )
Pubmed \| J Cardiothorac Vasc Anesth	N/A	-	10	Von Willebrand Factor Concentrate	憲齋蓋積淵鏇範築壓製(繭窪窪積憲襯構鹽遞鹹) = 蓋網顧構窪夢廠獵齋範醖艱壓觸築艱鬱鬱醖製 (鏇鏇廠網製齋鬱齋齋衊 )	-	2021-03-01
ISTH2020	N/A	冯·维勒布兰德病	8	Recombinant von Willebrand Factor (rVWF)	遞顧廠淵簾製蓋觸醖選(築鏇簾獵糧築顧獵醖糧) = 簾範築選獵鹽積鏇窪簾餘艱範衊鏇衊積鹹艱艱 (繭膚鑰積鏇醖鹹鑰鑰鏇 ) 更多	-	2020-07-12