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

The main aim of the study is to evaluate the effectiveness of prophylaxis with 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 rVWF for 12 months.
During the study, participants will visit the study clinic 6 times after treatment initiation.

开始日期2024-01-09

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT04985682 / Completed临床4期

Phase 4, Multicenter, Prospective, Interventional, Post-Marketing Study in Hemophilia A Patients in India Receiving ADVATE as On-Demand or Prophylaxis Under Standard Clinical Practice

The main aim of this study is to learn more about side effects of Advate when given as standard treatment to people with hemophilia A who have already been treated.
The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study. Participants will need to visit the study doctor 5 times in total during the study. During these visits, study data will be collected by the study doctor.

开始日期2022-01-14

申办/合作机构

Baxalta, Inc.

[+1]

CTRI/2021/10/037406 / Active, not recruiting临床4期

Phase 4, Multicenter, Prospective, Interventional, Post-Marketing Study in Hemophilia A Patients in India Receiving ADVATE as On-Demand or Prophylaxis Under Standard Clinical Practice - Nil

开始日期2021-11-01

申办/合作机构

Baxalta US, Inc.

[+1]

100 项与重组人凝血因子Ⅷ（Takeda）相关的临床结果

登录后查看更多信息

100 项与重组人凝血因子Ⅷ（Takeda）相关的转化医学

登录后查看更多信息

100 项与重组人凝血因子Ⅷ（Takeda）相关的专利（医药）

登录后查看更多信息

189

项与重组人凝血因子Ⅷ（Takeda）相关的文献（医药）

2024-04-01·Clinical Pharmacology & Therapeutics

A Generative and Causal Pharmacokinetic Model for Factor VIII in Hemophilia A: A Machine Learning Framework for Continuous Model Refinement

Article

作者: Smalbil, Louk ; Mathôt, Ron A A ; Janssen, Alexander ; Bennis, Frank C ; Cnossen, Marjon H

In rare diseases, such as hemophilia A, the development of accurate population pharmacokinetic (PK) models is often hindered by the limited availability of data. Most PK models are specific to a single recombinant factor VIII (rFVIII) concentrate or measurement assay, and are generally unsuited for answering counterfactual (“what‐if”) queries. Ideally, data from multiple hemophilia treatment centers are combined but this is generally difficult as patient data are kept private. In this work, we utilize causal inference techniques to produce a hybrid machine learning (ML) PK model that corrects for differences between rFVIII concentrates and measurement assays. Next, we augment this model with a generative model that can simulate realistic virtual patients as well as impute missing data. This model can be shared instead of actual patient data, resolving privacy issues. The hybrid ML‐PK model was trained on chromogenic assay data of lonoctocog alfa and predictive performance was then evaluated on an external data set of patients who received octocog alfa with FVIII levels measured using the one‐stage assay. The model presented higher accuracy compared with three previous PK models developed on data similar to the external data set (root mean squared error = 14.6 IU/dL vs. mean of 17.7 IU/dL). Finally, we show that the generative model can be used to accurately impute missing data (< 18% error). In conclusion, the proposed approach introduces interesting new possibilities for model development. In the context of rare disease, the introduction of generative models facilitates sharing of synthetic data, enabling the iterative improvement of population PK models.

2024-03-01·Haemophilia

Canadian clinical experience on switching from standard half‐life recombinant factor VIII (rFVIII), octocog alfa, to extended half‐life rFVIII, damoctocog alfa pegol, in persons with haemophilia A ≥ 12 years followed in a Comprehensive Hemophilia Care Program in Canada

Article

作者: Matino, Davide ; Iserman, Emma ; Oladoyinbo, Olayide ; Keepanasseril, Arun ; Chelle, Pierre ; Edginton, Andrea N ; Germini, Federico ; Iorio, Alfonso ; Decker, Kay ; Trinari, Elisabetta ; Chan, Anthony K C

AbstractIntroductionDamoctocog alfa pegol (BAY 94–9027, Jivi®) is an extended half‐life recombinant factor (F)VIII replacement, indicated for the treatment of haemophilia A in patients aged ≥12 years. Following introduction of damoctocog alfa pegol in Canada in 2020, there have been no reports on routine clinical effectiveness and satisfaction, when switching from a previous FVIII product in Canada.AimTo report changes in pharmacokinetics, effectiveness, utilization and patient satisfaction when switching to damoctocog alfa pegol prophylaxis from previous standard half‐life octocog alfa (BAY 81–8973, Kovaltry®) treatment.MethodsA single‐centre, intra‐patient comparison of pharmacokinetics and clinical outcomes was performed. Blood samples drawn once pre‐dose and ≥2 times post‐dose were measured by a one‐stage assay to assess pharmacokinetic parameters including area under the curve (AUC, primary endpoint). Patient‐reported outcomes data were collected using the Patient‐Reported Outcomes, Burdens and Experiences questionnaire (PROBE). Clinical outcomes included annualized bleeding rate (ABR) and factor utilization.ResultsDose‐normalized AUC was significantly increased after switch to damoctocog alfa pegol from octocog alfa. Median (quartile [Q]1; Q3) annualized bleeding rates were 0.67 (0.00; 1.33) with damoctocog alfa pegol and 1.33 (0.00; 2.67) with octocog alfa. Half of the patients receiving damoctocog alfa pegol prophylaxis experienced zero bleeds (n = 9, 50.0%) versus 38.9% (n = 7) of patients treated with octocog alfa. Patients’ good quality of life was maintained.ConclusionThis study provides routine clinical evidence supporting the benefits of switching from octocog alfa to damoctocog alfa pegol for patients with severe haemophilia A.

2024-01-01·Haemophilia

A global comparative field study to evaluate the factor VIII activity of efanesoctocog alfa by one‐stage clotting and chromogenic substrate assays at clinical haemostasis laboratories

Article

作者: Konkle, Barbara A ; Kitchen, Steve ; Seth Chhabra, Ekta ; Negrier, Claude ; Willemze, Annemieke ; Abad-Franch, Lydia ; Liu, Mingjie ; Santagostino, Elena ; Knobe, Karin ; Pipe, Steven ; Sadeghi-Khomami, Ali

AbstractIntroductionStructural and chemical modifications of factor VIII (FVIII) products may influence their behaviour in FVIII activity assays. Hence, it is important to assess the performance of FVIII products in these assays. Efanesoctocog alfa is a new class of FVIII replacement therapy designed to provide both high sustained factor activity levels and prolonged plasma half‐life.AimEvaluate the accuracy of measuring efanesoctocog alfa FVIII activity in one‐stage clotting assays (OSAs) and chromogenic substrate assays (CSAs).MethodsHuman plasma with no detectable FVIII activity was spiked with efanesoctocog alfa or a full‐length recombinant FVIII product comparator, octocog alfa, at nominal concentrations of 0.80 IU/mL, 0.20 IU/mL, or 0.05 IU/mL, based on labelled potency. Clinical haemostasis laboratories (N = 35) tested blinded samples using in‐house assays. Data from 51 OSAs (14 activated partial thromboplastin time [aPTT] reagents) and 42 CSAs (eight kits) were analyzed.ResultsEfanesoctocog alfa activity was reliably (±25% of nominal activity) measured across all concentrations using OSAs with Actin FSL and multiple other aPTT reagents. Under‐ and overestimation of FVIII activity occurred with some reagents. No specific trend was observed for any class of aPTT activators. A two‐ to three‐fold overestimation was consistently observed using CSAs and the OSA with Actin FS as the aPTT reagent across evaluated concentrations.ConclusionUnder‐ or overestimation occurred with some specific OSAs and most CSAs, which has been previously observed with other modified FVIII replacement products. Efanesoctocog alfa FVIII activity was measured with acceptable accuracy and reliability using several OSA methods and commercial plasma standards.

项与重组人凝血因子Ⅷ（Takeda）相关的新闻（医药）

2024-04-16

·药渡

4.17世界血友病日：血友病离治愈还有多远？

每年4月17日是世界血友病日，自18世纪被发现以来，血友病一直是医学界探索的难题。经过上百年的不懈努力，当下血友病主要治疗药物实则是经历了四代更迭：20世纪70年代初，人类开始使用血源性的凝血因子制品治疗血友病，以baxter的Recombinate为代表的第一代凝血因子药物应运而生；20世纪90年代，由于第一代血源性凝血因子药物存在过度依赖血浆带来的传染性病原体感染风险，baxter开发了第二代血友病治疗药物重组凝血因子产品Advate，之后该技术得到广泛推广，沿用至今；2014年，为解决重组凝血因子产品给药频率的临床需求，bioverativ与赛诺菲共同开发的Alprolix作为首个长效重组凝血因子制品在美国获批，开创了血友病治疗的第三代产品；2017年，为解决部分血友病患者的抗药物抗体并发症问题，罗氏开发了首个不依赖凝血因子的非因子替代治疗药物“艾美赛珠单抗”，成为了第四代血友病治疗产品。显然，人类在血友病治疗领域取得显著进步，过去很长一段时间，血友病治疗完成了从凝血因子到非凝血因子替代疗法的探索。但目前临床上对于半衰期短、关节损害并发症等血友病的治疗担忧依旧存在，以及临床上对更长效、更高效、更安全的药物需求仍未被满足。不过，随着近年来基因疗法的崛起以及部分基因疗法的获批上市，也逐渐给血友病治疗的新变革，也让人们真正看到了血友病“一针治愈”的曙光。两大类血友病A与血友病B血友病是一种X染色体连锁的隐性遗传性出血性疾病，病理机制为凝血因子基因缺陷导致其水平和功能减低而使血液不能正常凝固，主要患病表现为关节、肌肉、内脏和深部组织自发性出血或外伤出血后止血困难。按照缺乏的凝血因子不同，血友病可以分为两种类型：缺乏凝血因子FVIII（八因子）的为血友病A，缺乏凝血因子FIX（九因子）的为血友病B。还可以根据FVIII或FIX的活性水平，将血友病A和血友病B分为轻型、中型和重型。血友病的发病率没有明显的种族或地区差异，所有血友病患者中，血友病A患者占80%~85%，血友病B患者占15%~20%。由于血友病的遗传与性染色体有关，基因在性染色体的X染色体上，而女性的一对性染色体是XX，达成血友病的遗传条件相对“苛刻”，因此血友病患者患病以男性为主，女性极其罕见。根据弗若斯特沙利文数据，全球血友病患病人数复合增长率为1.3%，从2015年的74.2万上升到2019年的78.3万，预计到2030年患者人数将增长到89万人，血友病也是“高发”的罕见病之一，治疗方案也就受血友病患者人群的密切关注。现有疗法替代治疗占主导地位血友病治疗的主要目的是预防危及生命的出血和治疗肌肉和关节出血，目前血友病的治疗方案包括凝血因子替代疗法和非因子疗法。第一/二代产品：血源性与重组凝血因子凝血因子替代治疗的主要作用机制是通过健康凝血因子的替换和补充，在无出血时进行预防治疗，在出血发生时及时加强凝血功能，最初采用新鲜冷冻血浆、冷沉淀物，20世纪70年代初开始使用血源性的凝血因子制品，即血源性人凝血因子（血源FVIII和FIX），也是第一代血友病治疗药物。到20世纪90年代，一种不依赖血浆供应，降低了传染性病原体感染的风险的凝血因子制品问世（重组FVIII和FIX），成为了第二代血友病治疗药物。表1 凝血因子替代治疗第一/二代药物分类产品企业工艺第一代产品MonoclateCSL血源FVIIIRecombinateBaxter血源FVIIIHemofil MBaxter血源FVIIIAlphanateGrifols血源FVIIIProplexBaxter血源 FIXMononineCSL血源 FIXAlphaNineGrifols血源 FIX第二代产品AdvateBaxter重组FVIIIRecombinateBaxter重组FVIIIKogenate拜耳重组FVIIIKovaltry拜耳重组FVIIIHelixateCSL重组FVIIIXyntha辉瑞重组FVIIINovoeight诺和诺德重组FVIII安佳因神州细胞重组FVIIIBeneFlX辉瑞重组FIX图片来源：公开数据整理第三代产品：长效凝血因子2014年，首个长效重组凝血因子制品Alprolix在美国获批，通过FEG修饰、B区糖基化、Fc融合蛋白、白蛋白融合蛋白等方法长效化地重组FVIII或重组FIX。将原有凝血因子的半衰期延长一倍以上，减少了预防性治疗的给药频率，并有效提高了患者的依从性，成为血友病替代疗法的第三代治疗药物。表2 凝血因子替代治疗第三代药物分类产品企业工艺第三代产品AdynovateBaxterPEG 全长重组蛋白FVIIIKovaltry拜耳PEG 截断重组蛋白FVIIIN8-GP诺和诺德B 区糖基化蛋白FVIIIEloctate赛诺菲Fc 融合蛋白 FVIIIAfstylaCSL白蛋白融合蛋白 FVIIIAlprolixBioverativ/赛诺菲Fc 融合蛋白 FIXIdelvionCSL白蛋白融合蛋白 FIX图片来源：公开数据整理（欢迎补充）目前，已上市的三代血友病治疗药物中，第二代重组FVIII和FIX获批数量最多，据不完全统计，目前全球有超10款重组FVIII和FIX产品上市，Baxter旗下的Recombinate是全球首个上市的重组凝血因子（1992年获批），之后拜耳、辉瑞、诺和诺德等跨国巨头也投身重组凝血因子赛道，并相继推出了自己的产品。并且，在治疗格局上，我国血友病A/B两者间呈现相对显著的差异，对于血友病A患者而言，2021年以前其治疗基本依赖进口药品，价格相对昂贵，直至2021年7月神州细胞的安佳因作为国产第一款重组凝血Ⅷ因子获批上市，打破了重组凝血Ⅷ因子的进口垄断。之后，正大天晴的注射用重组人凝血因子Ⅷ等产品他也相继提交了上市申请，用药成本有望持续降低；而对于血友病B而言，其治疗药品近年来已基本实现了国产替代，且其在医保与厂家补贴之下，基本实现了零用药成本。第四代产品：非因子疗法虽然大多数血友病患者可以通过凝血因子替代疗法来进行防治，但是有一部分的血友病患者接受替代疗法后，症状未见缓解。据悉，大约25%的血友病A患者和5%的血友病B患者，在接受第Ⅷ/Ⅸ凝血因子治疗后，体内产生了注射因子的抑制剂（抗药物抗体），这是治疗过程中最严重的并发症之一。对于产生抑制剂的患者，原则上需要采用免疫耐受诱导（ITI）治疗，利用高水平的因子让这些抑制剂饱和。如果免疫耐受诱导不合适或者失败，这需要使用非因子疗法，例如使用艾美赛珠单抗、去氨基-8-D-精氨酸加压素( DDAVP)、解热镇痛治疗、抗纤维蛋白溶解药物等。表3 非因子疗法的相关分类治疗手段细分类别药物类型治疗原理治疗特点非因子治疗非因子替代治疗艾美赛珠单抗通过模拟 FⅧa 的辅因子功能，可同时桥接 FIXa 和 FX，使 FX在没有 FⅧ 的情况下得以继续激活，重新恢复生理性凝血通路。效果好，用药频次低，维持剂量给药频次最低可达每4周1次，但存在血栓性血管病的副作用，价格显著高于重组八因子产品去氨基-8-D-精氨酸加压素( DDAVP)DDAVP注射剂、鼻喷剂轻型和中型可能有效，重型患者无效疗效不及 FVIII解热镇痛治疗乙酰氨基酚和弱或强阿片类药物，或应用 COX-2 类解热镇痛药对重症患者无效治标不治本抗纤维蛋白溶解药物氨甲环酸、6-氨基己酸、止血芳酸等常用药物有氨甲环酸、6-氨基已酸、氨甲苯酸等。对口腔、舌、扁桃体、咽喉部出血及拔牙引起的出血有效，但对关节腔、深部肌肉和内脏出血疗效较差图片来源：公开数据整理其中，使用由罗氏研发的艾美赛珠单抗是非因子治疗中较为重要的一种，即非因子替代治疗，也被称为血友病治疗的第四代药物。2017年在美国获批上市，是一种双特异性单克隆抗体药物，其作用机制是在患者体内同时桥接凝血因子IXa(FIXa)和凝血因子X(FX)，通过模拟FⅧ的辅因子功能，使FX在FⅧ异常的情况下可以正常激活，从而重新恢复患者的凝血功能。艾美赛珠单抗是近20年来FDA批准的首个用于治疗A型血友病的创新药，根据罗氏财报，2023年艾美赛珠单抗销售额达45.95亿美元，同比增长16%，在罗氏畅销产品榜单中排名第二。2018年底，艾美赛珠单抗已在我国获批用于存在凝血因子Ⅷ抑制物的A型血友病患者。打破局限基因疗法点燃治愈希望虽然，替代治疗（含凝血因子和艾美赛珠单抗）在一定程度上的确缓解了血友病患者的症状，在血友病治疗市场占据了主导地位。但现有治疗方式依旧存在明显的弊端，如凝血因子在体内的代谢时间较短，大约在12小时至20多小时之间，因此患者一般情况下需要每周输注2-3次凝血因子来防止出血，并且需要终身维持输注；艾美赛珠单抗虽降低了用药频次，但仍需要维持最低每4周1次的用药需求，且存在血栓性血管病的副作用、费用也不低，目前国内艾美赛珠单抗仍未纳入医保，30mg的价格是8100元一支，60mg艾美赛珠的价格是16200元一支，需终身服药。为了从根本上解决这些问题，基因治疗应势而起。基因治疗通过输注正确的基因，使其在体内表达凝血因子，理论上可以使患者通过一次性的治疗实现凝血因子的永久表达，从而达到一次输注、终身治愈的目标。已上市产品截止目前，最常见的血友病基因疗法是使用AAV载体包装Ⅷ因子的基因。AAV载体通过载体递送到达患者靶细胞内维持游离状态，实现Ⅷ因子在靶器官内持续表达。2022年至今，全球范围内已获批上市了3款针对血友病的基因疗法，都是以AAV载体为载体的产品，即Roctavian、Hemgenix以及Beqvez。表4 血友病基因疗法产品药物名称首次上市时间首次审批机构研发企业适应症售价Roctavian2022.08EMABioMarin Pharmaceutical严重血友病A成人患者150万欧元Hemgenix2022.12FDAUniQure血友病B成人患者350万美元Beqvez2024.01Health Canada辉瑞18岁及以上中度至重度B型血友病且对AAV血清型Rh74的中和抗体检测为阴性的成年患者未公布图片来源：公开数据整理其中，辉瑞的Beqvez今年1月刚在加拿大获批上市用于治疗18岁或以上中重度至重度乙型血友病成人患者，尚未在美国获批上市，FDA于2023年6月接受了辉瑞的生物制品许可申请，预计将于2024年第二季度做出审批决定。根据辉瑞2022年12月所公布的BENEGENE-2积极数据，该基因疗法使患者的ABR降低了71%，年化凝血因子输注率降低了92%。根据研究者公开信息，最早接受基因治疗的一例血友病B患者已经达到接近十年的长期表达，目前基因治疗血友病至少能够保持凝血因子表达5-10年以上，但距离终生表达的期望还存在差距，对于丢失表达的患者，唯有寄希望未来通过基因治疗技术的改进和发展实施第二次和第三次基因治疗。临床阶段产品由于基因治疗被证实，确实为血友病患者带来了治愈希望，全球药企对血友病的基因疗法保持较高的研发热情，除已上市药物，目前全球范围内针对血友病基因疗法的管线超15条，其中有3条已进入临床Ⅲ期，含Sangamo/辉瑞的SB-525、Spark Therapeutics的SPK-8011以及信念医药的BBM-H901。表5 全球针对血友病的基因疗法临床Ⅱ期以上管线产品研发企业研发进度SB-525Sangamo/辉瑞临床Ⅲ期SPK-8011Spark Therapeutics临床Ⅲ期BBM-H901信念医药临床Ⅲ期DTX-201拜耳临床Ⅱ期ASC-618ASC Therapeutics临床Ⅱ期SHP-654Baxalta临床Ⅱ期TI-168Teralmmune inc临床Ⅱ期BAX-335Baxalta临床Ⅱ期Verbrinacogene setparvovecFreeline Therapeutics临床Ⅱ期VGB-R04天泽云泰临床Ⅱ期ZS-801至善唯新临床Ⅱ期图片来源：公开数据整理结语诚然，现有血友病治疗方案之下，诸多副作用等因素导致其新药临床需求迫切，但基因治疗一劳永逸的纠正血友病患者体内的基因异常或基因缺陷的理想与现实中5-10年的表达期却存在较大的心理预期差。另外，经济问题也是让血友病走向治愈的一道坎，虽然基因疗法有望实现治愈，但是高昂的价格阻碍了药物的大范围推广，uniQure上市半年却仅有1名患者接受了相关治疗，就算如今全球接受了血友病基因治疗的病患也是寥寥可数，多数血友病患者都是望而却步。总之，血友病治疗发展还需要多方共同努力，如企业研发更便捷有效的治疗药物、政府完善更便捷的支付支付方式、全社会提升对血友病的认知等，共同推进血友病治疗真正走向治愈。参考资料：《2024 CASH丨张磊教授：一次输注，终生治愈，血友病基因治疗前景可期》血液病研究院血液学研究所《三代血友病治疗药物及长效重组凝血因子简析》中国生物圈免责声明“药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！

基因疗法上市批准临床研究

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

登录后查看更多信息

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,

后查看更多信息

适应症	国家/地区	公司	日期
血友病A	美国	Takeda Pharmaceuticals U.S.A., Inc.	2003-07-25
血友病A	美国	Baxter Healthcare Corp.	2003-07-25

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
血友病A	临床3期	奥地利	Baxalta, Inc.	2004-04-01
血友病A	临床3期	西班牙	Baxalta, Inc.	2004-04-01
血友病A	临床3期	意大利	Baxalta, Inc.	2004-04-01
血友病A	临床3期	加拿大	Baxalta, Inc.	2004-04-01
血友病A	临床3期	瑞典	Baxalta, Inc.	2004-04-01
血友病A	临床前	加拿大	Baxalta, Inc.	2004-04-01
血友病A	临床前	西班牙	Baxalta, Inc.	2004-04-01
血友病A	临床前	瑞典	Baxalta, Inc.	2004-04-01
血友病A	临床前	奥地利	Baxalta, Inc.	2004-04-01
血友病A	临床前	意大利	Baxalta, Inc.	2004-04-01

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


NCT05042440 (Phase 1 sequential pharmacokinetic study, EHA2024)	临床1期	血友病A FVIII	-	Octocog alfa	(簾遞淵築蓋鏇窪顧憲築) = 3 treatment-emergent adverse events (TEAEs) while receiving efanesoctocog alfa in 1 patient (2 mild and 1 moderate) and none reported for other treatments. No TEAEs were serious, led to treatment discontinuation, or were deemed related to efanesoctocog alfa treatment. 積衊衊簾廠鬱觸廠繭遞 (鹹製醖夢鏇選顧廠願繭 )	积极	2024-05-14
				Rurioctocog alfa pegol
NCT04985682 (CTgov)	临床4期	血友病A	50	ADVATE	觸淵衊遞範積壓網遞觸(鹽膚蓋簾觸壓壓遞蓋糧) = 窪鑰餘遞觸憲製壓壓鏇積範繭鑰蓋積糧獵鏇壓 (積鑰鏇簾壓製製糧艱範, 顧顧壓憲製鑰膚糧憲蓋 ~ 願鹹積鑰餘獵廠艱構齋) 更多	-	2024-03-07
ISTH2022	N/A	血友病	-	Kogenate FS	(鬱壓鏇構餘範鹽襯繭鑰) = 製鹽願艱鹹廠襯構獵壓鏇窪獵壓構選糧餘憲築 (鏇範淵遞簾壓網遞遞蓋 ) 更多	-	2022-07-09
				Advate	(鬱壓鏇構餘範鹽襯繭鑰) = 鑰糧襯憲壓艱鹽衊糧範鏇窪獵壓構選糧餘憲築 (鏇範淵遞簾壓網遞遞蓋 ) 更多
EHA2021	N/A	血友病A	-	Moroctocog alpha	廠願積顧艱壓膚鑰構簾(鹹憲餘製鑰艱蓋製醖蓋) = 艱夢壓齋壓簾糧製醖夢願願鑰築顧壓觸築選顧 (襯醖簾艱艱選鑰選齋選 )	-	2021-06-09
				Plasma FVIII and Octocog alpha	廠願積顧艱壓膚鑰構簾(鹹憲餘製鑰艱蓋製醖蓋) = 醖製遞襯選醖壓繭壓淵願願鑰築顧壓觸築選顧 (襯醖簾艱艱選鑰選齋選 )
NCT02306694 (CTgov)	临床3期	血友病A \| 骨病	16	Advate	艱繭網築壓齋鏇積糧壓(憲壓選範鹽廠襯糧鹽襯) = 構糧鑰獵遞餘糧築醖鏇簾觸選糧醖繭衊製齋網 (壓膚選艱獵構糧積顧艱, 淵夢網膚廠遞選餘築選 ~ 憲繭選範襯衊膚壓蓋糧) 更多	-	2020-03-24
NCT01085344 (CTgov)	临床4期	血友病A	56	Recombinant Factor VIII (Advate/Helixate FS/KoegenateFS)	構艱醖範選製膚壓壓築(遞顧廠餘鏇淵鹹窪遞鑰) = 鑰顧遞遞範鹽衊醖繭蓋蓋夢鏇膚遞鑰艱餘範獵 (獵糧網醖衊鹽積顧願遞, 憲範壓構範簾鬱夢獵餘 ~ 獵窪淵鹽醖鹹淵網糧齋) 更多	-	2019-12-05
NCT03205163 (EXTEN-A, CTgov)	临床1/2期	血友病A	16	Advate (Advate 25 IU/kg)	繭遞齋夢顧願鏇艱糧齋(鬱鏇選製壓簾鹹憲選鏇) = 壓觸範窪繭膚繭鑰鹽製鹹鑰觸襯構鑰鹽遞齋艱 (餘憲窪餘鬱選獵積廠觸, 製積糧鏇觸網膚觸窪鬱 ~ 醖製艱獵艱齋鹽選網淵) 更多	-	2019-12-02
				Advate (Advate 65 IU/kg)	繭遞齋夢顧願鏇艱糧齋(鬱鏇選製壓簾鹹憲選鏇) = 範觸顧範糧積繭築顧選鹹鑰觸襯構鑰鹽遞齋艱 (餘憲窪餘鬱選獵積廠觸, 積簾願範廠鏇繭廠簾淵 ~ 顧蓋蓋範積夢鹽網窪鬱) 更多
NCT02483208 (Pubmed \| Clin Pharmacokinet)	临床1期	血友病A	18	BAY 81-8973	鑰積壓窪糧膚餘夢壓網(餘襯壓憲窪廠築窪糧鑰) = 鹽網衊網窪艱鬱衊觸艱構範醖廠獵鏇獵糧選醖 (構獵選膚憲憲鹽膚鹽製 ) 更多	-	2017-09-01
				Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method (rAHF-PFM)	鑰積壓窪糧膚餘夢壓網(餘襯壓憲窪廠築窪糧鑰) = 鬱鹽鹽簾願遞積淵遞糧構範醖廠獵鏇獵糧選醖 (構獵選膚憲憲鹽膚鹽製 ) 更多
EHA2017	N/A	血友病A	14	Octocog α	願齋鑰鹽壓顧鹽衊觸壓(築糧鬱淵襯淵顧餘範遞) = 餘鹹鹽窪蓋範觸簾衊鹹襯糧憲襯構鬱製醖憲積 (齋鏇選艱壓獵選願網襯 ) 更多	-	2017-05-18
NCT01486927 (AFFINITY \| CSL627_1001 \| Leopold II, CTgov)	临床2/3期	血友病A	175	rVIII-SingleChain+Octocog alfa	衊築獵繭繭獵鹹鏇網憲(鏇簾淵獵餘構蓋夢憲獵) = 膚醖淵觸鏇簾鏇艱網衊範壓選艱窪夢膚觸選艱 (夢鏇鹽齋夢製選醖網膚, 遞簾簾鏇膚淵衊蓋簾網 ~ 齋選顧簾鹽鹽築築衊願)	-	2016-08-09