Randomized, Active-controlled, Double-blind, Parallel Design Study to Evaluate the Efficacy and Safety of a Once-a-week Prophylaxis Treatment With BAY79-4980 Compared to Three Times-per-week Prophylaxis With rFVIII-FS in Previously Treated Patients With Severe Hemophilia A

A study to assess treatment with a new formulation of recombinant factor VIII reconstituted with liposomes (BAY79-4980) to evaluate whether a once-a-week treatment is safe and can prevent bleeds in subjects with severe haemophilia A.

开始日期2008-06-01

申办/合作机构

Bayer AG

NCT00629837 / Completed临床1期

A Randomized, Double-blind, Cross-over Study to Determine the Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980 in Previously Treated Patients With Severe Hemophilia A

The primary objective of this study is to determine the pharmacokinetic profile after single administration of two doses of BAY 79-4980 (high and low: 35 IU FVIII/Kg reconstituted in 22 mg and 13 mg of liposomes/Kg, respectively) compared to rFVIII-FS (35 IU/Kg reconstituted in 2.5 mL WFI/1000 IU) in PTPs aged 12 to 60 years with severe hemophilia A.

开始日期2005-09-01

申办/合作机构

Bayer AG

100 项与 BAY-794980(Bayer AG) 相关的临床结果

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项与 BAY-794980(Bayer AG) 相关的文献（医药）

2023-12-31·Journal of medical economics

Healthcare costs among hemophilia A patients in the United States treated with rurioctocog alfa pegol (FVIII-PEG) or antihemophilic factor (recombinant), FC fusion protein (rFVIIIFc) using real-world data

Article

作者: Princic, Nicole ; Farahbakhshian, Sepehr ; Schultz, Bob G ; Park, Julie ; Bullano, Michael ; Fan, Qi

AIMS:

To compare healthcare costs in patients with non-inhibitor hemophilia A treated with Rurioctocog Alfa Pegol (FVIII-PEG) versus Antihemophilic Factor (Recombinant), FC Fusion Protein (rFVIIIFc).

MATERIALS AND METHODS:

Administrative claims data from the Merative MarketScan Commercial (Commerical) and Medicaid (Medicaid) databases were used for these analyses. Males with non-inhibitor hemophilia A treated with FVIII-PEG or rFVIIIFc from 1 January 2016 to 31 March 2021 were identified (earliest treatment = index). Patients were required to have continuous database enrollment for six months before and after the index date. Follow-up was variable in length until disenrollment or study end. All-cause and hemophilia-related healthcare costs were reported per-patient per month [PPPM] and the average weekly dose during follow-up was compared between treatment groups. Generalized linear regressions were used to estimate multivariable-adjusted differences in total costs and weekly dosage in the two treatment groups.

RESULTS:

A total of 131 FVIII-PEG (66 Commercial; 65 Medicaid) and 204 rFVIIIFc (111 Commercial; 93 Medicaid) patients were eligible. Mean age was 20.5 and 24.4 for FVIII-PEG and rFVIIIFc in Commercial and 14.9 and 17.5 for FVIII-PEG and rFVIIIFc in Medicaid. PPPM mean (standard deviations [SD]) total healthcare costs in Commercially insured patients were $35,868 [$21,717] for FVIII-PEG vs $40,424 [$25,882] for rFVIIIFc. Costs in Medicaid were $27,495 [$23,243] for FVIII-PEG vs $30,237 [$28,430] for rFVIIIFc. After adjusting for baseline characteristics, the costs for rFVIIIFc (vs FVIII-PEG) were higher by $5,215 in Commercial and $3,895 in Medicaid, but the differences were not statistically significant (p > 0.05). Similar findings were observed for hemophilia-specific healthcare costs. The adjusted mean weekly dose was 6,047 vs 4,892 IU, p = 0.21 for FVIII-PEG vs rFVIIIFc in Commercial and 5,549 vs 7,228 IU, p = 0.07 for FVIII-PEG vs rFVIIIFc in Medicaid.

CONCLUSIONS:

Healthcare costs and treatment dosing were similar (p > 0.05) for non-inhibitor hemophilia A patients treated with FVIII-PEG and rFVIIIFc.

2023-11-01·Research and practice in thrombosis and haemostasis

Inhibitor development according to concentrate in severe hemophilia: reporting on 1392 Previously Untreated Patients from Europe and Canada

Article

作者: Lambert, Thierry ; Carcao, Manuel ; Gatt, Alexander ; Lassila, Riitta ; Kaczmarek, Radek ; Samji, Nasrin ; Rivard, Georges-Étienne ; Fischer, Kathelijn ; Iorio, Alfonso ; Peyvandi, Flora ; Hollingsworth, Rob ; Makris, Mike ; Bettle, Amanda

Background:

Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant.

Objectives:

To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B.

Methods:

The European Haemophilia Safety Surveillance (EUHASS) and Canadian Bleeding Disorders Registry (CBDR) have been monitoring adverse events overall and according to concentrate for 11 and 8 years, respectively. Inhibitors were reported quarterly, and PUPs completed 50 exposure days without inhibitor development annually. Cumulative inhibitor incidences and 95% confidence intervals (CIs) were compared without adjustment for other risk factors.

Results:

Fifty-six European and 23 Canadian centers reported inhibitor development in 312 of 1219 (26%; CI, 23%-28%) PUPs with severe hemophilia A and 14 of 173 (8%; CI, 5%-13%) PUPs with severe hemophilia B. Inhibitor development was lower on plasma-derived factor (F)VIII (pdFVIII, 20%; CI, 14%-26%) than on standard half-life recombinant FVIII (SHL-rFVIII, 27%; CI, 24%-30% and odds ratio, 0.67; CI, 0.45%-0.98%; P = .04). Extended half-life recombinant FVIII (EHL-rFVIII, 22%; CI, 12%-36%) showed an intermediate inhibitor rate, while inhibitor rates for Advate (26%; CI, 22%-31%) and Kogenate/Helixate (30%; CI, 24%-36%) overlapped. For other SHL-rFVIII concentrates, inhibitor rates varied from 3% to 43%. Inhibitor development was similar for pdFIX (11%; CI, 3%-25%), SHL-rFIX (8%; CI, 3%-15%), and EHL-rFIX (7%; CI, 1%-22%).

Conclusion:

While confirming expected rates of inhibitors in PUPs, inhibitor development was lower in pdFVIII than in SHL-rFVIII. Preliminary data suggest variation in inhibitor development among different SHL-rFVIII and EHL-rFVIII concentrates.

2023-01-01·Haemophilia : the official journal of the World Federation of Hemophilia

Area under the curve: Comparing the value of factor VIII replacement therapies in haemophilia A

Article

作者: Berndt, Cecilia ; Persson, Sofie ; Engstrand, Sara ; Trinczek, Annegret ; Berntorp, Erik ; Carlsson, Katarina Steen

Abstract:

Introduction:

In factor VIII (FVIII) prophylaxis for haemophilia A, cost comparisons have used price per international unit (IU) based on the once reasonable assumption of equivalent outcome per IU. Now, with several extended half‐life (EHL) products available, new outcome‐oriented ways to compare products are needed. Area under the curve (AUC) quantifies FVIII levels over time after infusion providing comparable data.

Aim:

To develop a decision analytical model for making indirect comparisons of FVIII replacement products based on AUC.

Methods:

A literature search identified 11 crossover studies with relevant pharmacokinetic data. A common comparator FVIII level curve was calculated using pooled data from selected studies. Absolute curves for other products were estimated based on relative differences to the common comparator (% difference vs the anchor). Three scenarios were investigated: (1) Kogenate® versus Kovaltry® and Jivi®; (2) Advate® versus Elocta®, NovoEight®, Kovaltry, Adynovate®, Afstyla®, and ReFacto®; and (3) Jivi versus Elocta, Adynovate, and Kogenate. Sensitivity analyses investigated effects of assay type and dose.

Results:

In scenario 1, Jivi (+50%) and Kovaltry (+14%) showed larger AUCs versus Kogenate. In scenario 2, EHL products, Elocta and Adynovate, had the largest AUC (+64% and +58%, respectively) versus Advate. Compared with all other products in scenario 3, Jivi had the largest AUC by +13%–28%.

Conclusion:

This analysis concludes that EHL products differ in relative AUC, have a larger AUC compared with standard half‐life, and thus, different FVIII levels over time after infusion. This model may aid decision makers in the absence of head‐to‐head data.

项与 BAY-794980(Bayer AG) 相关的新闻（医药）

2023-02-24

·药智网

大药企接力裁员，涉及辉瑞、拜耳等

今年以来，裁员降薪的重锤接连砸向各行各业。医药行业也频频爆出裁员消息，有些Biotech裁员比例甚至高达50%-95%，而员工薪资也是大幅缩水。近日，又有大药企开启裁员计划，涉及辉瑞、拜耳、强生等。拜耳伯克利工厂裁员55人据外媒Endpoint News消息，德国拜耳正在美国加利福尼亚州伯克利的一家工厂实施裁员。根据最新的工人调整和再培训报告（WARN）显示，拜耳已经在该家工厂解雇了55人，员工于1月30日收到通知，裁员日期在3月底。拜耳承认，裁员是公司重组的一部分。日前，拜耳正在实施一项“离职选举计划”，为55岁及以上且至少为公司服务10年的员工提供退休服务。该公司表示，受影响的人将有资格获得遣散费。拜耳在声明中表示，“通过此次组织重组，我们的目标是确保我们拥有现场基础设施和专业人员，以适应不断变化的投资组合需求。”并补充说，此举是一项“成本控制措施”。根据拜耳的网站显示，该公司伯克利工厂于1992年开始运营，以生物制造和生物制剂开发为核心，现有员工约1000人。拜耳原计划再增加1000人，以扩大其细胞和基因疗法，但如今也不能幸免裁员的阵痛。一直以来，该工厂主要负责生产拜耳的血友病治疗药物，如Kogenate、Kovaltry和Jivi。但由于罗氏制药Hemliba的强势竞争，这些药物的销售额已经趋于弱势。去年，罗氏Hemliba的销售额达到41亿美元，而拜耳的这三款药物去年前三季度的销售额仅为6.41亿美元。值得一提的是，2018年，罗氏Hemliba获得批准的时候，拜耳曾在伯克利工厂裁员227人，并关闭了德国的一家小型工厂。另外，拜耳还表示，“我们在进行裁员的同时，将仍然专注于伯克利工厂生物技术业务的转型，从蛋白质疗法的研发和制造扩展到为患者提供新的治疗模式，如细胞疗法。”辉瑞加州裁员196人拜耳的裁员不是个案，WARN还透露了“宇宙大药厂”辉瑞的裁员信息。据悉，辉瑞正在美国圣地亚哥地区的研究中心裁员196人，该研究中心专注于肿瘤学和疫苗，裁员将在4月19日完成。值得一提的是，今年1月下旬，辉瑞在美国加利福尼亚州拉霍亚和康尼狄格州格罗顿的工厂也进行了裁员，具体人数不明。当时，辉瑞对外界表示计划放弃一些罕见病、肿瘤学的早期项目，以“加大公司早期外部创新力度”。强生两部门裁减37人除了拜耳、辉瑞外，WARN最新信息显示，强生公司位于同一地点的两个部门DePuy Synthes Products和Medical Device Business Services，近期也合计裁减了37名员工。这个月初，强生曾宣布，计划合并疫苗与传染病业务部门作为一个整体进行运营。这项改革预计将导致在全球范围内进行大规模裁员，但并未透露相关裁员数量和职位。当时，据外媒报道，强生旗下的杨森已在New Jersey和Pennsylvania两个地区进行裁员。其实，在此之前，已经有多家医械企业宣布裁员，包括安进、默克、百特、卫材、BMS，以及全球血制品巨头基立福(Grifols)等。无论是哪家企业传出裁员消息，都时刻拨动着医药人敏感的神经。根据“MedTalent医人才”统计，今年刚刚过去的45天，全球至少已经有30家大健康企业宣布裁员，数量几乎与2022年第一季度持平。显而易见，裁员风暴还将继续蔓延。那么，在裁员潮下的打工人，该怎么办？来源 | 思齐俱乐部（药智网获取授权转载）撰稿 | 四叶草责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。阅读原文，是昨天最受欢迎的文章哦

基因疗法高管变更疫苗细胞疗法

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 BAY-794980(Bayer AG) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
血友病A	临床2期	俄罗斯	Recoly NV	2005-10-01

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适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00623727 (CTgov)	临床2期	血友病A	143	rFVIII-FS/pegylated liposomes (BAY79-4980) (rFVIII-FS/Pegylated Liposomes (BAY79-4980))	築廠鹽艱憲襯夢顧壓糧(網繭廠膚範糧夢網範艱) = 築鏇網鹹簾膚鏇鑰願觸艱壓顧遞窪糧齋憲糧窪 (獵壓鏇齋憲鹽願淵鑰製, 簾艱衊壓鹽鹹願構廠衊 ~ 積淵製構憲鏇選築夢蓋) 更多	-	2011-08-17
				rFVIII-FS/WFI (BAY14-2222) (rFVIII-FS/WFI (BAY14-2222))	築廠鹽艱憲襯夢顧壓糧(網繭廠膚範糧夢網範艱) = 鏇獵構鹽夢窪糧糧艱積艱壓顧遞窪糧齋憲糧窪 (獵壓鏇齋憲鹽願淵鑰製, 鹽願觸構憲鹽鏇觸製鹽 ~ 膚鬱積願壓鬱夢糧憲繭) 更多