更新于：2024-05-03

Eftrenonacog alfa

艾诺凝血素α

更新于：2024-05-03

概要

概要

基本信息

药物类型

融合蛋白

别名

Coagulation factor IX recombinant immunoglubulin g1 fusion protein、Coagulation factor IX recombinant immunoglubulin G1 fusion protein;、Coagulation Factor IX(Long-Acting, Recombinant Fc Fusion Protein)

+ [17]

靶点

factor IX

作用机制

factor IX刺激剂(凝血因子IX刺激剂)、凝血途径激活剂、凝血因子替代物

治疗领域

遗传病与畸形血液及淋巴系统疾病其他疾病

在研适应症

血友病B出血

非在研适应症-

原研机构

Sobi Analytics Ltd.

在研机构

Bioverativ, Inc.

Swedish Orphan Biovitrum AB

Bioverativ Therapeutics, Inc.

+ [3]

非在研机构-

最高研发阶段批准上市

首次获批日期

美国 (2014-03-28),

出血

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)、临床急需境外新药 (中国)

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序列信息

Sequence Code 169138

来源: *****

Sequence Code 616723820

来源: *****

关联

项与艾诺凝血素α 相关的临床试验

NCT05856266 / Terminated临床4期

An 18-month Low-interventional Prospective, Multicentre Study to Assess Joint Outcomes in Patients With Haemophilia A or B on Prophylaxis With Efmoroctocog Alfa or Eftrenonacog Alfa

The goal of this low-interventional study is to describe the overall joint health in patients with haemophilia A or haemophilia B prophylactically treated with rFVIIIFc or rFIXFc.
The main question it aims to answer is the:
• Evaluation of the overall joint status as detected by ultrasound in haemophilia A and B patients treated with rFVIIIFc or rFIXFc prophylaxis over the 18-month study period.
Participants will come to 6-monthly visits during the 18-month long study period and will perform an ultrasound with the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol at each visit. At baseline and end of study visits, the patients will be assessed with the clinical scoring system Haemophilia Joint Health Score (HJHS) and complete patient questionnaires. Retrospective data from patient medical records will also be collected for at least 6 months before enrolment in the study.

开始日期2023-08-24

申办/合作机构

Swedish Orphan Biovitrum AB

CTIS2022-502921-16-00 / Not yet recruiting

An 18-month low-interventional prospective, multicentre study to assess joint outcomes in patients with haemophilia A or B on prophylaxis with efmoroctocog alfa or eftrenonacog alfa - Sobi.HAEM89-007

开始日期2023-06-13

申办/合作机构

Swedish Orphan Biovitrum AB

NCT05662319 / Recruiting临床3期

A Phase 3, Single-arm, Multicenter, Multinational, Open-label, One-way Crossover Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged ≥ 12 Years With Severe Hemophilia A or B With or Without Inhibitory Antibodies to Factor VIII or IX

This is a multicenter, multinational, open-label, one-way cross-over, Phase 3, single-arm study for treatment of hemophilia.
The purpose of this study is to measure the frequency of treated bleeding episodes with fitusiran in male adult and adolescent (≥12 years old) participants with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX who have switched from their prior standard of care treatment.
The total study duration will be up to approximately 50 months (200 weeks, 1 study month is equivalent to 4 weeks) and will include:
A screening period up to approximately 60 days,
A standard of care (SOC) period of approximately 6 study months (24 weeks),
A fitusiran treatment period of approximately 36 study months (144 weeks),
An antithrombin (AT) follow-up period of approximately 6 study months (24 weeks) but may be shorter or longer depending on individual participants AT recovery.
The frequency for telephone visits will be approximately every 2 weeks. For site visits the frequency will be approximately every 8 weeks during the SOC period and approximately every 4 weeks during the fitusiran treatment period. If applicable and if allowed by local regulation, home and/or remote visits may be conducted during the study

开始日期2023-02-01

申办/合作机构

Sanofi

100 项与艾诺凝血素α 相关的临床结果

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100 项与艾诺凝血素α 相关的转化医学

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100 项与艾诺凝血素α 相关的专利（医药）

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133

项与艾诺凝血素α 相关的文献（医药）

2024-03-01·Biosensors and Bioelectronics

A ferrocene-based hydrogel as flexible electrochemical biosensor for oxidative stress detection and antioxidation treatment

Article

作者: Zhang, Haiqi ; Ma, Lie ; Li, Yan ; Hu, Hongtao ; Wang, Jinze

Real-time sensing of reactive oxygen species (ROS) and timely scavenging of excessive ROS in physiological environments are critically important in the diagnosis and prevention of ROS-related diseases. To solve the mismatch problem between conventional rigid ROS biosensors and biological tissues in terms of both modulus and composition, here, we present a flexible ferrocene-based hydrogel biosensor designed for oxidative stress detection and antioxidation treatment. The hydrogel was fabricated through a supramolecular assembly of ferrocene-grafted polyethylenimine (PEI-Fc), sodium alginate (SA), and polyvinyl alcohol (PVA). Multiple non-covalent interactions, including electrostatic interactions between PEI-Fc and SA, hydrophobic interactions and π-π stacking among ferrocene groups, and the PVA crystalline domain, synergistically improve the mechanical properties of the PVA/SA/PEI-Fc hydrogel. The flexible PVA/SA/PEI-Fc hydrogel biosensor exhibited a broad detection range for hydrogen peroxide (H₂O₂), from 0 to 120 μM, using the differential pulse voltammetry method. Furthermore, the hydrogel demonstrated effective ROS scavenging and oxygen generation performance, desirable biocompatibility, and satisfactory antibacterial activity, making it suitable for biological interfaces. In vitro studies revealed that the PVA/SA/PEI-Fc hydrogel could monitor H₂O₂ concentration in the proximity of inflammatory cells, and effectively scavenge ROS to protect cells from oxidative stress damage. This all-in-one multifunctional hydrogel, integrating both sensing and treatment functions, holds great promise for clinical applications in the diagnosis and management of ROS-related diseases.

2024-01-01·British Journal of Clinical Pharmacology

A new population pharmacokinetic model for recombinant factor IX‐Fc fusion concentrate including young children with haemophilia B

Article

作者: Cnossen, Marjon H ; Bukkems, Laura H ; Payne, Jeanette ; Mathôt, Ron A A ; Chowdary, Pratima ; Tait, R Campbell ; Goedhart, Tine M H J ; Leebeek, Frank W G ; Fijnvandraat, Karin ; Bagot, Catherine N ; Coppens, Michiel ; Curry, Nicola ; Koopman, Sjoerd F ; Collins, Peter W ; Mulders, Trevor M ; Mathias, Mary

Abstract:

Aims:

Recombinant factor IX Fc fusion protein (rFIX‐Fc) is an extended half‐life factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients aged ≥12 years. The aim was to externally evaluate the predictive performance of the published rFIX‐Fc population PK model for patients of all ages and develop a model that describes rFIX‐Fc PK using real‐world data.

Methods:

We collected prospective and retrospective data from patients with haemophilia B treated with rFIX‐Fc and included in the OPTI‐CLOT TARGET study (NTR7523) or United Kindom (UK)‐EHL Outcomes Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A new population PK model was constructed using nonlinear mixed‐effects modelling.

Results:

Real‐world data were obtained from 37 patients (median age: 16 years, range 2–71) of whom 14 were aged <12 years. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction error of −48.8%. The new model showed a lower median prediction error (3.4%) and better described rFIX‐Fc PK, especially for children aged <12 years. In the new model, an increase in age was correlated with a decrease in clearance (P < .01).

Conclusions:

The published population PK model significantly underpredicted FIX activity levels. The new model better describes rFIX‐Fc PK, especially for children aged <12 years. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population.

2024-03-01·International Journal of Biological Macromolecules

Ferrocene crosslinked and functionalized chitosan microspheres towards bio-based Fenton-like system for the removal of organic pollutants

Article

作者: Lu, Guoqiang ; Zhang, Yongmin ; Mu, Meng ; Xie, Huan

Dye-containing wastewater treatment has been a major long-term global challenge. For this purpose, a novel bio-based microspheres (CS-FC) with high specific surface area (63.24 m²·g^-1) and nano-channels (17.95 nm) was prepared using chitosan as the framework and ferrocene as a crosslinking active group. CS-FC not only has the ability to rapidly enrich methyl orange (MO) through hydrogen-bonding and electrostatic attraction, but also almost completely degrades it in the presence of H₂O₂/K₂S₂O₈ through a synergistic radical/non-radical mechanism under the activating effect of ferrocene. Without H₂O₂/K₂S₂O₈, the maximum MO adsorption capacity of CS-FC is in the range 871-1050 mg·g^-1, and conforms to a Langmuir isothermal model with pseudo-second-order kinetics. In the presence of H₂O₂/K₂S₂O₈, the removal of MO dramatically increased from 32 % to nearly 100 % after incubation for 60 min, due to the simultaneous formation of highly reactive ¹O₂ and ·OH. The significant contribution from ¹O₂ endowed CS-FC/H₂O₂/K₂S₂O₈ with high universality for degrading various organic pollutants (including azo dyes and antibiotics), a wide pH window (2-8), and low sensitivity to co-existing ions. Such cost-effective, recyclable porous bio-based microspheres are suitable for heterogeneous Fenton-like catalysis in organic wastewater treatment that rely on synergistic radical/non-radical reaction pathways.

项与艾诺凝血素α 相关的新闻（医药）

2024-04-26

·PRNewswire

Sobi® receives positive CHMP opinion recommending approval of efanesoctocog alfa for once-weekly treatment of haemophilia A

STOCKHOLM, April 26, 2024 /PRNewswire/ -- Sobi® today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion recommending approval of efanesoctocog alfa, for the treatment and prevention of bleeds and perioperative prophylaxis in haemophilia A. Efanesoctocog alfa is a once-weekly and high-sustained factor VIII replacement therapy for patients of all ages and any disease severity. Efanesoctocog alfa provides children, adolescents and adults with normal to near-normal factor VIII activity levels (above 40%) for a significant part of the week with once-weekly dosing, reaching trough levels of 15% in adults and adolescents at day 7. This results in significantly improved protection from bleeds compared to existing factor VIII prophylaxis. The CHMP positive opinion will now be submitted to the European Commission for a marketing authorisation decision. "Today's announcement marks a major milestone in haemophilia care and moves us one step closer to bringing efanesoctocog alfa to patients in the EU. Efanesoctocog alfa sustains high factor VIII activity levels throughout the week, giving patients confidence in the protection it can provide to prevent bleeds, manage surgery, and resolve bleeds. With the potential to significantly improve treatment outcomes and quality of life for people living with haemophilia A, we are excited about the positive impact this treatment could have around the world," said Lydia Abad-Franch, MBA, Head of Research, Development, and Medical Affairs, and Chief Medical Officer at Sobi. Haemophilia A is a rare, lifelong genetic condition in which the body does not produce enough, or makes dysfunctional, factor VIII – a protein that is essential for blood clotting. It occurs in about one in 5,000 male births annually, and more rarely in females. People with haemophilia can experience bleeding episodes that can cause pain, irreversible joint damage and life-threatening haemorrhages. Clinical outcomes have improved over time thanks to significant advances in the treatment options available, however important unmet clinical and social needs still exist for those living with the condition. The recommendation from the CHMP is based on the results from the pivotal phase 3 studies: XTEND-1 in adults and adolescents and XTEND-Kids in children, which evaluated the efficacy and safety of efanesoctocog alfa. These studies demonstrated that once-weekly efanesoctocog alfa prophylaxis (50 IU/kg) provided significant bleed protection (mean ABR <1 and 80-88% of patients free from spontaneous bleeds) in people with severe haemophilia A of any age. The data also showed substantial improvement in joint health, physical health, pain and overall quality of life when comparing week 52 and baseline measurements.1 No factor VIII inhibitors were observed in the efanesoctocog alfa clinical program. Efanesoctocog alfa was first approved in the US in February 2023 by the US Food and Drug Administration (FDA). The FDA previously granted efanesoctocog alfa Breakthrough Therapy designation in May 2022 — the first factor VIII therapy to receive this designation, Fast Track designation in February 2021, and Orphan Drug designation in 2017. References von Drygalski. A., Chowdary. P., Kulkarni. R., et al. Efanesoctocog Alfa Prophylaxis for Patients with Severe Haemophilia A. N Engl J Med 2023; 388:310-318. About XTEND-1 XTEND-1 was an open-label, non-randomized interventional study with two parallel assignment arms. Participants in the prophylaxis arm received a weekly prophylactic dose of efanesoctocog alfa for 52 weeks. Participants in on-demand arm received efanesoctocog alfa on demand for 26 weeks followed by a switch to weekly prophylaxis for another 26 weeks. XTEND-1 evaluated efficacy, safety and pharmacokinetics in 159 previously treated patients ≥12 years of age with severe haemophilia A. About XTEND-Kids XTEND-Kids was an open-label, non-randomised interventional, single-arm study. Participants received a weekly prophylactic dose of efanesoctocog alfa for 52 weeks. XTEND-Kids evaluates efficacy, safety, and pharmacokinetics in 74 previously treated patients <12 years of age with severe haemophilia A. About efanesoctocog alfa Efanesoctocog alfa [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein] (formerly BIVV001) is a new class of recombinant factor VIII therapy with the potential to deliver near-normal factor activity levels for a significant part of the week, improving bleed protection in a once-weekly dose for people with haemophilia A. Efanesoctocog alfa builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN® polypeptides to extend its time in circulation. It is the only therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on current factor VIII therapies. It is approved and marketed as ALTUVIIIO™ [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] by Sanofi in the United States, Japan, and Taiwan. The European Commission granted Orphan Drug designation in June 2019. About the Sanofi and Sobi collaboration Sobi and Sanofi collaborate on the development and commercialisation of Alprolix® and Elocta®/Eloctate®. The companies also collaborate on the development and commercialisation of efanesoctocog alfa, or ALTUVIIIO™ in the US. Sobi has final development and commercialisation rights in the Sobi territory (essentially Europe, North Africa, Russia, and most Middle Eastern markets). Sanofi has final development and commercialisation rights in North America and all other regions in the world excluding the Sobi territory. About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people's lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the centre of our ambitions. Sanofi is listed on (EURONEXT: SAN) and (NASDAQ: SNY). Sobi® Sobi® is a specialised international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of haematology, immunology, and specialty care, Sobi has approximately 1,800 employees across Europe, North America, the Middle East, Asia, and Australia. In 2023, revenue amounted to SEK 22.1 billion. Sobi's share (STO: SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn. Contacts For details on how to contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here. This information was brought to you by Cision The following files are available for download: SOURCE Swedish Orphan Biovitrum AB

临床结果孤儿药上市批准临床3期快速通道

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

2024-04-02

·BioSpace

Avalo Therapeutics Appoints Biotech Leaders to Board of Directors

Appointments include industry veterans Aaron Kantoff, Jonathan Goldman, and Samantha Truex as Independent Directors Board of Director appointments in conjunction with Avalo’s recent acquisition of AVTX-009, an anti-IL-1β mAb, and up to $185 million private placement financing WAYNE, Pa. and ROCKVILLE, Md., April 02, 2024 (GLOBE NEWSWIRE) -- Avalo Therapeutics, Inc. (Nasdaq: AVTX) today announced the addition of multiple biotech leaders to its Board of Directors. The Avalo Board brings together a team with expertise spanning finance, business operations, drug discovery and clinical development. “I am honored to announce these additions to our Board of Directors and welcome their operational expertise as we pursue the promise of rapidly developing AVTX-009 in hidradenitis suppurativa and other devastating autoimmune conditions," said Garry A. Neil, MD, CEO and Chairman of the Board at Avalo. The recent board appointments include Aaron Kantoff, Jonathan Goldman, and Samantha Truex as Independent Directors. Aaron Kantoff is a founder and Managing Partner of Scion Life Sciences. He has spent over a decade specializing in founding, building and investing in biotech companies. Aaron was a founding board member of Tourmaline Bio (Nasdaq: TRML), Centessa Pharmaceuticals, and RayzeBio, which was recently acquired by Bristol Myers Squibb. From 2011 until 2019, Aaron was a Partner at Apple Tree Partners (ATP), a life sciences venture capital firm. During his time at ATP, he was a board member of several companies, including Akero Therapeutics , Corvidia (acquired by Novo Nordisk), and Syntimmune (acquired by Alexion Pharmaceuticals, Inc.). Aaron received a B.S. in finance and international business from the New York University Leonard N. Stern School of Business. Jonathan Goldman, MD has 30 years of experience across life sciences as a CEO, Chief Medical Officer, investor, and senior executive. He currently serves as the CEO of Clinical ink, a global life science company that brings data, technology, and patient-centric research together. Prior to Clinical ink, Jonathan served as the CEO and a board member of Abzena and was previously the CEO of Aptuit. He has also held senior executive positions at ICON plc and Point Biomedical Corp. in addition to holding appointments as Associate Clinical Professor of Medicine in the division of Cardiology at the University of California San Francisco, and as an Attending Cardiologist at the San Francisco Veterans Administration Medical Center. Jonathan trained in medicine at St. Bartholomew’s Hospital Medical College, in London and in cardiology at St. George’s Hospital Medical School, London. He received a BSc in immunology, as well as MBBS and MD degrees in medicine from the University of London, UK. He was awarded MBAs by Columbia University in New York and the University of California at Berkeley. Samantha Truex is a seasoned biotech executive with almost 30 years of industry experience, including the last five years in CEO roles. Sam is on the board of Artios Pharma and has previously served on the boards of Hotspot Therapeutics, iPierian (acquired by Bristol Myers Squibb) and True North (acquired by Bioverativ Inc.). Sam was the founding CEO of Upstream Bio, the CEO of Quench Bio, COO of Synlogic and CBO for Padlock Therapeutics. Previously, Sam was Vice President of Corporate Development at Biogen Inc. where she led transactional business development activities and served as program executive for now-marketed products FAMPYRA,® ELOCTATE™ and ALPROLIX™. Sam also previously worked in Corporate Development at Genzyme, Chiron Diagnostics and in consulting for Health Advances. Sam earned a BA in biology from Dartmouth College, a BE in biomedical engineering from the Thayer School at Dartmouth and an MBA from the Tuck School at Dartmouth. Samantha also chairs the Board of Advisors for Thayer School of Engineering at Dartmouth and is a member of the Board of Advisors for Life Science Cares. About AVTX-009 AVTX-009 is a humanized monoclonal antibody (IgG4) that binds to interleukin-1β (IL-1β) with high affinity and neutralizes its activity. IL-1β is a central driver in the inflammatory process. Overproduction or dysregulation of IL-1β is implicated in many autoimmune and inflammatory diseases. IL-1β is a major, validated target for therapeutic intervention. There is evidence that inhibition of IL-1β could be effective in hidradenitis suppurativa and a variety of inflammatory diseases in dermatology, gastroenterology, and rheumatology. About Avalo Therapeutics Avalo Therapeutics is a clinical stage biotechnology company focused on the treatment of immune dysregulation. Avalo’s lead asset is AVTX-009, an anti-IL-1β mAb, targeting inflammatory diseases. Avalo’s pipeline also includes quisovalimab (anti-LIGHT mAb) and AVTX-008 (BTLA agonist fusion protein). For more information about Avalo, please visit Forward-LookingStatements This press release may include forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. Such forward-looking statements are subject to significant risks and uncertainties that are subject to change based on various factors (many of which are beyond Avalo’s control), which could cause actual results to differ from the forward-looking statements. Such statements may include, without limitation, statements with respect to Avalo’s plans, objectives, projections, expectations and intentions and other statements identified by words such as “projects,” “may,” “might,” “will,” “could,” “would,” “should,” “continue,” “seeks,” “aims,” “predicts,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential,” or similar expressions (including their use in the negative), or by discussions of future matters such as: the intended use of the proceeds from the private placement; integration of AVTX-009 into our operations, including trial design and IND preparation and filing for the planned Phase 2 trial; drug development costs, timing of trials and trial results, and other risks, particularly for AVTX-009, including reliance on investigators and enrollment of patients in clinical trials; reliance on key personnel; regulatory risks; general economic and market risks and uncertainties, including those caused the war in Ukraine and the Middle East; and those other risks detailed in Avalo’s filings with the Securities and Exchange Commission, available at . Actual results may differ from those set forth in the forward-looking statements. Except as required by applicable law, Avalo expressly disclaims any obligations or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Avalo’s expectations with respect thereto or any change in events, conditions or circumstances on which any statement is based. For media and investor inquiries: Christopher Sullivan, CFO Avalo Therapeutics, Inc. ir@avalotx.com 410-803-6793 or Chris Brinzey ICR Westwicke Chris.brinzey@westwicke.com 339-970-2843

高管变更并购

100 项与艾诺凝血素α 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10522	-	B02BD04	DB11608

研发状态

适应症	最高研发状态	国家/地区	公司
出血	批准上市	美国更多	Bioverativ Therapeutics, Inc. 更多
血友病B	批准上市	澳大利亚更多	Sanofi-Aventis Australia Pty Ltd. 更多

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临床结果

适应症

分期

评价

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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


NCT01027364 (B-LONG, ISTH2023)	临床3期	血友病B	-	Recombinant Factor IX Fc Fusion Protein	憲齋壓糧餘鏇獵觸遞繭(顧選鏇選繭遞醖淵醖鑰) = 壓衊獵衊廠鹽顧壓蓋憲齋膚膚選蓋壓積積艱繭 (願構遞窪夢膚獵製醖繭 )	-	2023-06-24
NCT01027364 (B-LONG, ISTH2023)	临床3期	血友病B	-	Recombinant Factor IX Fc Fusion Protein	憲齋壓糧餘鏇獵觸遞繭(顧選鏇選繭遞醖淵醖鑰) = 繭膚餘衊願製獵夢願襯齋膚膚選蓋壓積積艱繭 (願構遞窪夢膚獵製醖繭 )	-	2023-06-24
ISTH2022	N/A	血友病B	-	SHL FIX	願選積窪蓋廠築夢鏇願(鑰壓顧顧壓憲鹽鹽觸鏇) = 繭鹹構鑰製積醖廠鹹鏇範餘衊齋夢齋餘襯積築 (網願齋獵艱積齋顧鏇餘 )	-	2022-07-09
ISTH2022	N/A	血友病B	-	rFIXFc	願選積窪蓋廠築夢鏇願(鑰壓顧顧壓憲鹽鹽觸鏇) = 遞繭觸壓鏇選衊顧窪構範餘衊齋夢齋餘襯積築 (網願齋獵艱積齋顧鏇餘 ) 更多	-	2022-07-09
B-MORE (ISTH2022)	N/A	血友病B	117	Prophylactic rFIXFc treatment	築襯窪鹹選糧醖鏇願蓋(積網鑰壓網憲網鹹築艱) = 衊範鏇製夢襯顧製艱膚蓋憲窪糧鬱鑰鹽艱鬱構 (壓築繭襯鬱艱淵願遞網 )	-	2022-07-09
ISTH2021	N/A	出血	38	rFIXFc	繭夢窪鏇襯廠鑰鑰襯窪(鬱膚網鏇選憲顧膚遞廠) = 製蓋繭製齋獵簾窪鹽淵糧糧齋餘構遞壓網齋構 (蓋鬱製憲膚夢糧艱網顧 )	-	2021-07-17
ISTH2021	N/A	出血	38	SHL FIX	繭夢窪鏇襯廠鑰鑰襯窪(鬱膚網鏇選憲顧膚遞廠) = 範鏇顧膚淵範網衊齋簾糧糧齋餘構遞壓網齋構 (蓋鬱製憲膚夢糧艱網顧 )	-	2021-07-17
NCT02234310 (PUPs B-LONG, Pubmed \| Blood Adv) 人工标引	临床3期	血友病B	33	rFIXFc	蓋夢蓋衊廠淵襯膚鹹醖(鹹遞餘憲鑰願鏇艱淵繭) = 膚願衊網襯齋憲願築餘鬱糧齋鏇鬱蓋遞衊遞糧 (膚鏇築製網鬱鹹網積壓, 0.08 ~ 15.76) 更多	积极	2021-07-13
NCT02234310 (CTgov)	临床3期	血友病B \| 出血	33	rFIXFc	窪鏇願衊獵簾願窪夢簾(積齋鏇鹽鹹築網鹽選糧) = 願襯繭鑰鬱選觸觸網鹽鑰衊衊選築壓膚顧窪網 (簾築獵艱艱築築獵醖窪, 淵繭襯鏇醖窪廠遞鑰餘 ~ 壓築餘鹽淵夢觸糧鹹醖) 更多	-	2020-07-31
ISTH2020	N/A	血友病B	23	Recombinant Factor IX Fc Fusion Protein Concentrate	糧鬱窪觸鹹獵鏇選餘鏇(鏇齋願糧夢範積鏇願餘) = 鏇構鏇網遞齋襯選壓蓋廠艱製醖壓餘鏇顧顧窪 (鏇鏇繭鑰蓋鬱積鏇觸願 ) 更多	-	2020-07-12
ISTH2020	N/A	-	-	rFIXFc	鏇範襯簾艱選鏇鹽範醖(鹹選膚鏇鑰艱簾鹽蓋願) = 鹽餘糧憲夢醖淵淵獵餘繭觸獵夢壓鑰獵積夢餘 (餘願顧壓餘築憲鹽鏇網 ) 更多	-	2020-07-12
ISTH2020	N/A	血友病B	40	N9-GP	鑰窪選網膚艱鑰顧築構(遞鹹夢衊廠淵獵夢壓簾) = 製網襯糧餘鑰遞繭選鏇簾網觸夢鹽顧願製憲積 (遞艱淵獵構繭壓鑰鹽餘 )	-	2020-07-12
NCT01440946 (CTgov)	临床3期	血友病B \| 出血	30	FIX+rFIXFc (Participants < 6 Years Old)	醖憲糧壓鏇襯顧獵積鏇(繭願淵壓廠齋積餘獵衊) = 鑰襯選糧艱獵鹽衊顧築獵鏇製糧構鹹鏇築願衊 (繭顧積齋鑰憲構選製窪, 醖齋鹹構夢遞觸鏇鹽夢 ~ 鑰夢鬱選鏇鏇膚獵膚網) 更多	-	2015-06-18
NCT01440946 (CTgov)	临床3期	血友病B \| 出血	30	FIX+rFIXFc (Participants 6 to < 12 Years Old)	醖憲糧壓鏇襯顧獵積鏇(繭願淵壓廠齋積餘獵衊) = 觸艱襯餘繭鬱選觸鏇願獵鏇製糧構鹹鏇築願衊 (繭顧積齋鑰憲構選製窪, 糧積糧獵觸壓壓觸餘鹽 ~ 簾積醖簾繭淵繭觸膚餘) 更多	-	2015-06-18