百特公布A型血友病新药BAX 855（长效版ADVATE）新的临床数据

百特公布A型血友病新药BAX 855（长效版ADVATE）新的临床数据

来源：生物谷 2015-02-12 20:33

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2015年2月12日讯 /生物谷BIOON/ --血液病巨头百特国际（Baxter International）近日在芬兰赫尔辛基举行的第八届欧洲血友病及相关疾病协会（EAHAD）年会上公布了A型血友病新药BAX 855一项关键III期研究的额外疗效和安全性数据。新数据扩展了此前公布的实验结果，该研究中，BAX 855达到了控制和预防出血发作及日常预防性治疗的主要终点；与按需治疗相比，每2周注射一次的预防性治疗方案，使年平均出血率（ABR）降低了95%。研究结果支持了百特于2014年12月向FDA提交的BAX 855的监管申请。

BAX 855是基于百特已上市产品ADVATE研发的一种半衰期延长的重组凝血因子VIII（rFVIII），开发用于A型血友病的治疗。ADVATE是百特的龙头产品，上市时间超过10年，是全球处方量最多的FVIII产品。BAX 855是ADVATE的长效版，如果获批，BAX 855将成为12岁及以上A型血友病患者一种重要的新治疗选择。

该前瞻性关键III期研究，在137例既往治疗过的12岁及以上A型血友病患者中开展，研究中患者分配至按需治疗（10-50 IU/kg，n=17）或每2周一次预防性治疗（40-50 IU/kg，n=120）。数据表明，与按需治疗（on-demand）相比，每2周注射一次的预防性治疗（prophylaxis）方案，使平均年出血率降低了95%（1.9% vs 41.5%）。此外，BAX 855能够有效治疗出血发作，96%的出血事件经1次或2次输注（平均剂量29.0 IU/kg）能够得到有效控制。几乎所有（96.2%）出血发作的治疗评级为优秀或良好。预防性治疗组，有40%的患者经历无出血发作。此外，BAX 855药代动力学数据表明，BAX 855的半衰期是ADVATE的1.4-1.5倍，支持了I期临床试验的结果。研究中，无一例患者体内产生针对BAX 855的抗体，同时也未发生治疗相关的严重副作用。

在欧盟监管方面，百特表示，一旦BAX 855的儿科临床试验完成，将在2016年向欧洲药品管理局（EMA）提交该药的上市许可申请（MAA）。

BAX 855是百特龙头产品血液疾病药物Advate的增强版。ADVATE是一种全长重组FVIII产品，未添加任何血液添加剂，适用于A型血友病患者出血的治疗和预防，不适用于血管性血友病（vWD）的治疗，该药已获全球64个国家批准。BAX 855利用了专有的聚乙二醇化（PEGylation）技术，旨在延长蛋白在体内的活性持续时间。该专有技术已应用于多种已上市药物。

A型血友病，又称典型血友病，是一种由于缺乏凝血因子 VIII 或凝血因子 VIII 蛋白缺陷而导致的遗传病。（生物谷Bioon.com）

英文原文：Baxter Presents Additional Data from Pivotal Study of BAX 855, Extended Half-Life Investigational Recombinant FVIII Based on ADVATE FOR Hemophilia A

DEERFIELD, Ill., February 11, 2015 - Baxter International Inc. (NYSE:BAX) today presented additional efficacy and safety data from the Phase III pivotal study of BAX 855, an investigational, extended half-life recombinant factor VIII (rFVIII) treatment for hemophilia A based on ADVATE [Antihemophilic Factor (Recombinant)] at the 8th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) in Helsinki, Finland.

The new data expand on the previously disclosed topline results from the pivotal trial, which found that BAX 855 met the study's primary endpoint in the control and prevention of bleeding episodes and routine prophylaxis. Patients in the twice-weekly prophylaxis arm of the trial experienced a 95 percent reduction in median annualized bleed rate (ABR) as compared to those in the on-demand arm (1.9 vs. 41.5, respectively). The study findings supported Baxter's December 2014 submission for approval of BAX 855 to the United States Food and Drug Administration (FDA).

"These pivotal trial results provide evidence to support the efficacy profile of BAX 855 in controlling, preventing or reducing the frequency of bleeding episodes when administered prophylactically twice weekly. Our goal with BAX 855 is to extend the interval between infusions while maintaining a similar efficacy profile to ADVATE," said John Orloff, M.D., vice president and global head of research and development for Baxter BioScience.

The prospective, global, multi-center, open-label, two-arm Phase III study evaluated BAX 855 among 137 previously treated hemophilia A patients (PTP) who were 12 years or older. Patients were assigned either to twice weekly prophylaxis (40-50 IU/kg, n=120) or on-demand treatment (10-50 IU/kg, n=17). In addition to a reduced ABR, BAX 855 was also effective in treating bleeding episodes, 96 percent of which were controlled with one or two infusions at a median dose of 29.0 IU/kg per infusion. Treatment was rated excellent or good for nearly all episodes (96.2%). In the prophylactic group (n=101), 40 percent of patients experienced no bleeds. The study also showed that BAX 855 pharmacokinetics offered a 1.4-1.5-fold extended half-life compared to ADVATE with a median infusion interval of 3.6 days, supporting the findings from the Phase I trial.

No patients developed inhibitors to BAX 855 and no treatment-related serious adverse events, including hypersensitivity, were reported. Seven adverse reactions in six patients, including headache, diarrhea, nausea, and flushing were reported.

Baxter's continuation study for patients who completed the pivotal trial and the Phase 3 study among previously treated patients under the age of 12 with severe hemophilia A remain ongoing. Upon completion of the pediatric study, Baxter expects to file for marketing authorization with the European Medicines Agency in 2016.

BAX 855 is based on ADVATE, a full-length FVIII molecule with more than
11 years of real-world patient experience. Through a collaboration with Nektar Therapeutics (NASDAQ: NKTR), BAX 855 leverages proprietary PEGylation technology designed to prolong the amount of factor VIII available for use in the body. This proprietary technology has been used for 15 years in a number of approved medicines that treat chronic or serious conditions.

About ADVATE
ADVATE is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency or classic hemophilia) for:

Control and prevention of bleeding episodes.
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Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

ADVATE is not indicated for the treatment of von Willebrand disease.

ADVATE has a demonstrated efficacy and safety profile. ADVATE is a full-length (derived from the complete FVIII gene) recombinant FVIII product that is processed without any blood-based additives. Because no blood-derived components are added at any stage of the manufacturing process, the potential risk of transmitting pathogens that may be carried in blood-based additives is eliminated. There have been no confirmed reports of transmission of HIV, HBV or HCV with rFVIII treatments.

ADVATE is the world's most prescribed FVIII treatment. It is currently approved in 66 countries worldwide, including the United States, Canada, 28 countries in the European Union, Algeria, Argentina, Australia, Brazil, Chile, China, Colombia, Ecuador, Hong Kong, Iceland, Iraq, Israel, Japan, Kuwait, Macau, Malaysia, Mexico, Morocco, New Zealand, Norway, Panama, Puerto Rico, Qatar, Russia, Saudi Arabia, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Tunisia, Turkey, Ukraine, Uruguay, and Venezuela.

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