2013年6月7日美国食品药品监督管理局(FDA)批准Rixubis[凝血因子IX(重组)Coagulation Factor IX (Recombinant)]为在16岁和以上有血友病B人们中使用。Rixubis是适用于为控制和预防出血发作，围手术期(从为手术住院时间延伸至出院时间阶段)处理，和常规使用防止和减少出血发作频数(预防)。
一种遗传性血液凝固疾病主要影响男性，血友病B是因子IX基因突变所致和导致因子IX的缺乏。在美国血友病B影响约3,300人。有血友病B个体可能经受潜在地严重出血，主要进入关节，关节可能被这类出血破坏。
美国FDA生物制品评价和研究中心主任Karen Midthun，M.D. 说：“因第一个重组凝血因子IX特别适用于为常规预防防止出血，Rixubis成为对保护血友病B患者我们武器库中的新武器，”“这个批准提供患者和医生用另一种治疗选择预防或减少出血发作频数。”
Rixubis是一种通过重组DNA技术生产的纯制蛋白。它不含人或动物各种蛋白。在单次使用小瓶中的冰冻干燥粉供应和在用无菌水重建配制后通过静脉注射给药。当为常规预防出血发作使用时，每周给药2次。
在总共 73例男性患者年龄12和65 岁间接受Rixubis为常规预防或因对出血症状反应需要(按需)的多中心研究中评价Rixubis的疗效。总之，在预防研究中当与有历史性接受按需治疗患者比较时，患者有年出血率较低75%。正在儿童人群中进行另外研究。
尽管可能发生严重副作用包括过敏性反应(危及生命的过敏性反应)，在临床研究中患者观察到的最常见副作用是味觉障碍(味觉扭曲)，肢体疼痛，和非典型血液检验结果。
Rixubis有总部在加州西湖村Baxter Healthcare Corporation 制造。
RIXUBIS[凝血因子IX(重组)Coagulation Factor IX (Recombinant)]
为静脉注射，为溶液冻干粉
美国初次批准：2013
一般描述
RIXUBIS[凝血因子IX(重组)]是一种用重组DNA技术生产的纯制蛋白。其氨基酸序列与血浆来源因子IX的Ala-148等位基因型相同，和其结构和功能特性与血浆来源因子IX相似。RIXUBIS通过一个遗传工程化CHO细胞株生产。在RIXUBIS的制造或制剂化任何阶段未加入人或动物蛋白。CHO细胞株分泌重组因子IX至确定的细胞培养介质不含激素，和重组因子IX通过色谱不需要单克隆抗体步骤的纯化过程。这个过程包括经确证的病毒灭活/去除步骤，亦即溶剂/去垢剂处理和15 nm纳滤[nanofiltration]。通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳评价RIXUBIS主要是单一组分。RIXUBIS的比活性为每毫克蛋白≥200国际单位。因子IX 预激活[preactivation]，用活性分析测量因子IXa/因子IX百分率为≤0.03%。用体外用基于凝血活酶时间(aPTT)-一阶段凝固分析测定对世界卫生组织对因子IX浓缩物标准校正测定国际单位效力。因子IX效力结果可能受在分析中所用aPTT试剂类型和参比标准影响；曾观察到差别直至40%。
RIXUBIS被制剂化成为无菌，无热原冻干粉将用静脉给药注射用无菌水重建配制。它不含任何防腐剂和可得到含标示在单次使用小瓶上以国际单位表示的标示量的因子IX 活性。每小瓶含标示250，500，1000，2000或3000 国际单位的重组凝血因子IX。冻干粉配制后，所有剂量强度都产生透明，无色溶液。赋形剂的浓度为：
作用机制
有血友病B患者凝血因子IX缺乏，有效止血需要此因子。用RIXUBIS治疗短暂替代缺失的凝血因子IX
适应证和用途
（1）在有血友病B成年中控制和预防出血发作。
（2）在有血友病B成年中围手术期处理。
（3） 在有血友病B成年中常规预防防止或减少出血发作频数。
RIXUBIS不适用于对诱发免疫耐受性有血友病B患者。
剂量和给药方法
只为配制重建后静脉使用。
控制和预防出血发作和围手术期处理：
每公斤体重1个国际单位RIXUBIS增加因子IX的循环活性0.9国际单位/dL。
初始剂量：
需要国际单位=体重(kg)×愿望因子IX增加(正常%或IU/dL)×观测到恢复倒数(IU/kg每IU/dL).
维持剂量依赖于出血或手术类型，止血挑战的强度，和直至实现伤口适当愈合天数。(2.2)
常规预防:
每公斤体重40至60国际单位每周2次。
剂型和规格
可得到单次使用小瓶中含冰冻干燥粉RIXUBIS标称值250，500，1000，2000或3000国际单位。
禁忌证
以下患者不要使用：
（1）已知对RIXUBIS或其赋形剂包括仓鼠蛋白超敏性。
（2）弥散性血管内凝血(DIC)。
（3）纤维蛋白溶解征象。
警告和注意事项
（1）可能发生超敏性反应，包括过敏性反应。如果出现症状，停止RIXUBIS和给予适当治疗。患者也可能发生对仓鼠(CHO)蛋白超敏性，在产品中存在痕量。
（2）可能发生对RIXUBIS的中和抗体(抑制剂)。如果未达到期望的因子IX血浆活性水平，或如用适当剂量不能控制出血，进行分析测量因子IX抑制剂浓度。
（3）在有因子IX抑制剂血友病B患者用因子IX产品诱导免疫耐受性后曾报道肾病综合症。
（4）使用含因子IX产品曾伴有发生血栓栓塞性并发症。
不良反应
在临床研究中在>1%受试者观察到最常见不良反应为：味觉障碍，肢体疼痛，和对furin抗体检验阳性。
为报告怀疑不良反应，联系Baxter Healthcare Corporation电话1-866-888-2472或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.
特殊人群中使用
妊娠：无人类或动物数据。只有明确需求才使用。
对患者咨询信息和FDA-批准患者说明书见17。

FDA Approves Baxter’s RIXUBIS as First Recombinant Factor IX Treatment for Routine Prophylaxis of Hemophilia B
Approval brings patients first new rFIX treatment option in more than 15 years

DEERFIELD, Ill.--(BUSINESS WIRE)--Baxter International Inc. (NYSE:BAX) today announced that the United States Food and Drug Administration (FDA) has approved RIXUBIS [Coagulation Factor IX (Recombinant)] for routine prophylactic treatment, control of bleeding episodes, and perioperative management in adults with hemophilia B. RIXUBIS is the first new recombinant factor IX (rFIX) approved for hemophilia B in more than 15 years and is the only rFIX indicated for both routine prophylaxis and control of bleeding episodes in the U.S. for adult patients living with this chronic condition. Hemophilia B is the second most common type of hemophilia and is the result of insufficient amounts of clotting factor IX, a naturally occurring protein in blood that controls bleeding.1
''Baxter has long been a leader in the support of people living with bleeding disorders with its innovative products and programs,'' said Val Bias, chief executive officer of the National Hemophilia Foundation (NHF). ''We applaud their ongoing commitment to the hemophilia community, demonstrated once again with now the first prophylactic treatment approved in the U.S. for adults living with hemophilia B.''
The approval is based on a Phase I/III study demonstrating that twice-weekly prophylactic treatment with RIXUBIS for six months achieved a median annualized bleed rate (ABR) of 2.0 with 43 percent of patients experiencing no bleeds. In this study, no patients developed an inhibitory antibody to FIX and no cases of anaphylaxis were reported. One patient developed a transient antibody to furin. The most common adverse reactions observed in >1% of subjects in clinical studies were: dysgeusia, pain in extremity, and positive test for furin antibody. The study was presented at the 54th Annual Meeting and Exposition of the American Society of Hematology (ASH) in Atlanta.
''RIXUBIS is a welcome addition to our leading portfolio of hemophilia treatments, providing a much-needed treatment option for the thousands of people living with hemophilia B,'' said Ludwig Hantson, Ph.D., president of Baxter's BioScience business. ''This approval moves us one significant step forward in our pursuit of a bleed-free world, one patient at a time.''
For the prophylaxis regimen to prevent or reduce frequency of bleeding episodes, RIXUBIS dosing of 40 to 60 IU per kg twice weekly may be used. Five dosage options will be available to provide the opportunity for patients to use a single vial to dose RIXUBIS. A BAXJECT II Needle-less Transfer device will be included in each package of RIXUBIS.
Baxter was granted orphan-drug designation by the FDA as part of the RIXUBIS application, a special status given to a product that would address an unmet need for people with a rare disease or condition. Baxter expects to file for marketing authorization for RIXUBIS in the European Union later this year.
About the Pivotal Study
The approval is based on a pivotal Phase I/III prospective, open-label, uncontrolled, multicenter study that investigated the pharmacokinetics, efficacy and safety of RIXUBIS in 73 previously-treated patients (between 12 and 65 years of age) with severe (factor IX level <1 percent) or moderately severe (factor IX level ≤2 percent) hemophilia B. Patients received RIXUBIS either for prophylaxis and/or for the treatment of bleeding episodes on an on-demand basis, and were exposed to a factor IX-containing product on ≥150 days. Fifty-nine patients received RIXUBIS for prophylaxis twice-weekly, and 56 of them received treatment for a minimum of three months. An additional 14 patients received RIXUBIS for the treatment of bleeding episodes only, and had to have at least 12 documented bleeding episodes requiring treatment within 12 months prior to enrollment.
The majority of patients taking RIXUBIS had arthropathy at screening (88 percent) and target joints (66 percent). Treatment was individualized based on the severity, cause and site of bleed and of the total 249 bleeding episodes, the majority (211; 84.7 percent) were treated with 1-2 infusions.
About RIXUBIS
RIXUBIS [Coagulation Factor IX (Recombinant)] is a recombinant factor IX (rFIX) protein for both routine prophylaxis and control of bleeding episodes in adults with hemophilia B. RIXUBIS is the first new rFIX approved to treat hemophilia B in more than 15 years and is the only rFIX approved by the FDA for both routine prophylaxis and control of bleeding episodes in this chronic condition.
Indications for RIXUBIS
RIXUBIS [Coagulation Factor IX (Recombinant)] is an antihemophilic factor indicated for:
•Control and prevention of bleeding episodes in adults with hemophilia B.
•Perioperative management in adults with hemophilia B.
•Routine prophylaxis to prevent or prevent or reduce the frequency of bleeding episodes in adults with hemophilia B.
RIXUBIS is not indicated for induction of immune tolerance in patients with hemophilia B.
Important Risk Information for RIXUBIS
RIXUBIS is contraindicated in patients who have:
•Known hypersensitivity to RIXUBIS or its excipients including hamster protein
•Disseminated intravascular coagulation (DIC)
•Signs of fibrinolysis
Hypersensitivity reactions, including anaphylaxis, have been reported with factor IX-containing products. Early signs of allergic reactions, which can progress to anaphylaxis, include angioedema, chest tightness, hypotension, lethargy, nausea, vomiting, paresthesia, restlessness, wheezing, and dyspnea. Immediately discontinue administration and initiate appropriate treatment if allergic- or anaphylactic-type reactions occur.
Development of neutralizing antibodies (inhibitors) to factor IX may occur. Regularly evaluate patients for the development of factor IX inhibitors by appropriate clinical observations and laboratory tests. If expected factor IX plasma activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor IX inhibitor concentration. Patients with factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to RIXUBIS.
Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with factor IX inhibitors. The safety and efficacy of using RIXUBIS for immune tolerance induction have not been established.
The use of factor IX containing products has been associated with the development of thromboembolic complications.
The most common adverse reactions observed in >1% of subjects in clinical studies were: dysgeusia, pain in extremity, and positive test for furin antibody.
The following class adverse reactions have been seen with another recombinant factor IX: inadequate factor IX recovery, inhibitor development, anaphylaxis, angioedema, dyspnea, hypotension, and thrombosis.
Please see the RIXUBIS full Prescribing Information at: www.baxter.com/downloads/healthcare_professionals/products/RIXUBIS_PI.pdf.
About Hemophilia B
Hemophilia B is the second most common type of hemophilia (also known as Christmas disease) and is the result of insufficient amounts of clotting factor IX, a naturally occurring protein in blood that controls bleeding.1 Approximately 26,000 people worldwide, including more than 4,000 in the U.S., have been diagnosed with hemophilia B.2 Hemophilia B is often a debilitating, chronic disease with complications that include bleeding episodes, hemophilic arthropathy (bleeding into a joint) and hospitalization.3
About Baxter in Hemophilia
Baxter has more than 60 years experience in hemophilia and has introduced a number of therapeutic firsts for hemophilia patients. The company has the broadest portfolio of hemophilia treatments in the industry and is able to meet individual therapy choices, providing a range of options at each treatment stage. The company’s work is focused on optimizing hemophilia care and improving the lives of people living with hemophilia A and B worldwide. Its diverse pipeline includes longer-acting therapies for hemophilia A, potential new treatments for hemophilia B (including gene therapy), von Willebrand disease and a recombinant treatment for patients with inhibitors.
About Baxter International Inc.
Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.