Turoctocog alfa

Octapharma will present new clinical and scientific findings for wilate® and Nuwiq® New findings in von Willebrand disease (VWD) and haemophilia A, will be presented by leading experts in a Satellite Symposium, as well as an oral and six poster presentations Presentations will include new data on the efficacy and safety of wilate® prophylaxis in people with von Willebrand disease (VWD) LACHEN, Switzerland, Jan. 17, 2024 /PRNewswire/ -- Showcasing wilate® at EAHAD 2024 WIL-31 is the largest prospective prophylaxis study in VWD with an on-demand run-in study as an intra-individual patient comparator. The study shows that wilate® prophylaxis is highly effective at reducing bleeding rates in children and adults with all types of VWD and across examined bleeding sites. The results provide compelling evidence for the use of regular prophylaxis in people with VWD. "The new data from the WIL-31 study provide strong evidence for the use of wilate® prophylaxis in people with all types of VWD. The findings have led to the approval of wilate ® as prophylaxis in the US, thereby expanding the therapeutic options for these patients" – Larisa Belyanskaya, Senior Vice President and Head of IBU Haematology. A deep-dive into the findings from the WIL-31 study will be showcased during Octapharma's Satellite Symposium 'Shifting prophylaxis paradigms in VWD: The WIL-31 study in focus': Jan Astermark (Sweden) will explore the underutilisation of prophylaxis in VWD compared to haemophilia A Robert F. Sidonio Jr. (US) will discuss how the findings from WIL-31 have challenged the status quo of prophylaxis in VWD The efficacy of wilate ® prophylaxis will be explored in three interactive cases of patients in the WIL-31 study: - Child living with VWD presented by Robert F. Sidonio Jr. from Atlanta - Adult living with frequent nosebleeds presented by Ana Boban from Zagreb - Female experiencing heavy menstrual bleeding presented by Csongor Kiss from Debrecen The Satellite Symposium will take place on Wednesday, February 7, 17:30–18:45 (CET), in Panorama Room 2. The importance of preventing frequent nosebleeds in people with VWD, and the efficacy of wilate ® prophylaxis in this setting, will be presented by Ana Boban in the oral SLAM presentation 'Regular prophylaxis with a plasma-derived von Willebrand factor/factor VIII concentrate is effective for reducing nosebleeds in children and adults with von Willebrand disease' (OR04) on Friday, February 9, 08:30–10:00 CET, Session 6 SLAM. Two poster presentations provide additional insights into the findings of the WIL-31 study: PO213: No accumulation of factor VIII and von Willebrand factor during prophylaxis with a plasma-derived von Willebrand factor/factor VIII concentrate during the WIL-31 study PO194: Managing von Willebrand disease with inhibitors during prophylaxis with a plasma derived von Willebrand factor/factor VIII concentrate – The WIL-31 study Showcasing Nuwiq® at EAHAD 2024 Beyond its role in the coagulation cascade, emerging evidence indicates that FVIII influences platelet and endothelial cell function. Replacement therapy with recombinant FVIII (rFVIII) concentrates has become a mainstay of treatment for people with haemophilia A; however, it is unknown if there is a difference in how modifications of rFVIII concentrates impact platelet and endothelial cell functionality. Binding of Nuwiq® to activated platelets in vitro was found to be greater compared with other rFVIII concentrates, while in separate research Nuwiq® showed stronger effects on endothelial cell function compared with other rFVIII concentrates: PO027: Impact of differential binding of recombinant factor VIII concentrates to platelets on platelet functionality PO024: Investigating the role of factor VIII in endothelial cell function In rare diseases such as haemophilia A, it is not possible to directly compare treatments in a clinical study. In such instances, indirect treatment comparisons can be used to compare the effects of different treatments. One such well-established indirect comparison method is matching-adjusted indirect comparison (MAIC). MAICs were used to compare the efficacy of personalised, pharmacokinetic-guided prophylaxis with Nuwiq® versus other treatments: PO041: Personalised prophylaxis with simoctocog alfa versus standard prophylaxis with efanesoctocog alfa in haemophilia A, a matching-adjusted indirect comparison PO042: Personalised prophylaxis with simoctocog alfa versus standard emicizumab prophylaxis in haemophilia A, a matching-adjusted indirect comparison "Octapharma's continuing commitment to improving the lives of patients is at the core of our values. Supporting clinical and scientific research projects is integral to how we achieve this commitment, and we are excited to present the results of such research at EAHAD 2024" – Olaf Walter, Board Member and Head of International Business Units at Octapharma. About Octapharma 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: Immunotherapy, Haematology 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 centres across Europe and the US. Octapharma has 40 years of experience in patient care. About Nuwiq ® Nuwiq® (simoctocog alfa) is a 4th generation recombinant factor VIII (rFVIII) protein, produced in a human cell line without chemical modification or fusion with any other protein1. It is cultured without additives of human or animal origin, is devoid of antigenic non-human protein epitopes and has a high affinity for von Willebrand factor1. Nuwiq® treatment has been assessed in nine1-3 completed clinical trials which included 201 previously treated patients (190 individuals)1 and 108 previously untreated patients2 with severe haemophilia A. Nuwiq® is available in 250 IU, 500 IU, 1,000 IU, 1,500 IU, 2,000 IU, 2,500 IU, 3,000 IU and 4,000 IU presentations4. Nuwiq® is approved for use in the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital FVIII deficiency) across all age groups4. About wilate ® wilate® is a high-purity human von Willebrand factor/factor VIII (VWF/FVIII) concentrate, that undergoes two virus inactivation steps during its production5. No albumin is added as a stabiliser5. The purification processes result in a 1:1 ratio of VWF to FVIII that is similar to normal plasma5. wilate® contains a VWF triplet structure and content of large high molecular weight multimers similar to normal human plasma5. wilate® is available in 500 IU and 1,000 IU presentations.6 wilate® is indicated for the prevention and treatment of haemorrhage or surgical bleeding in von Willebrand disease (VWD), when desmopressin (DDAVP) alone is ineffective or contra-indicated, and for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency)6. The indication for prophylaxis in the US is detailed in the updated prescribing information available here: wilate Full Prescribing Information (wilateusa.com) Octapharma press releases are specifically for health specialist/medical media and are not for consumer press.  References Lissitchkov T et al. Ther Adv Hematol 2019; 10:2040620719858471. Liesner RJ et al. Thromb Haemost 2021; 121:1400-8. Octapharma AG; Data on file. Nuwiq® Summary of Product Characteristics. Stadler M et al. Biologicals 2006; 34:281-8. wilate® Summary of Product Characteristics. Logo: Contacts: Ivana Spotakova Global Communications Manager ivana.spotakova@octapharma

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。