ST LOUIS (MD Consult) - The US Food and Drug Administration (FDA) has approved ATryn (antithrombin [recombinant]) for preventing perioperative and peripartum thromboembolic events in hereditary antithrombin-deficient patients, according to the drug's manufacturers, GTC Biotherapeutics and OVATION Pharmaceuticals, Inc.

ATryn is not indicated for treating thromboembolic events in hereditary antithrombin-deficient patients. It is the first transgenically produced therapeutic protein and the first recombinant antithrombin approved in the United States. Along with the approval of ATryn, the FDA's Center for Veterinary Medicine also approved GTC's New Animal Drug Application, the first of its kind to regulate genetically engineered animals. This is now required for a recombinant technology used to develop transgenic animals, such as the goats that produce recombinant antithrombin.

GTC has granted OVATION the right to market ATryn in the United States and pursue further clinical development. The companies expect ATryn to be available in the second quarter of 2009.

People with hereditary antithrombin deficiency are at increased risk for venous thromboembolic events, including pulmonary embolism and deep vein thrombosis, which can be life threatening, particularly in high-risk situations. Antithrombin is a natural anticoagulant that plays an important role in controlling the formation of blood clots. Purified recombinant antithrombin has the same amino-acid sequence as antithrombin derived from human plasma.

ATryn was developed to provide a safe and consistent supply of recombinant antithrombin.

"With FDA approval of ATryn, we can help ensure that patients with hereditary antithrombin deficiency ... have access to much needed therapy," said Jeffrey S. Aronin, OVATION president and chief executive officer.

The safety and efficacy of ATryn were established in clinical studies conducted in hereditary antithrombin-deficient patients with a history of thromboembolic events in the United States, Europe, and Canada. During these studies, ATryn was shown to prevent the formation of clinically overt thromboembolic events. Post marketing studies will be performed to assess safety and immunogenicity after repeated dosing.

The prevalence of hereditary antithrombin deficiency in the general population is approximately 1 in 2,000 to 1 in 5,000. Half these patients may experience a thrombosis before age 25 years old and, according to one study, up to 85% may experience a thromboembolic event by age 50.

ATryn is the first recombinant antithrombin product approved in the world and the first antithrombin product that has been approved through the centralized procedure in the European Union. It is now also the first recombinant antithrombin product approved by the FDA.

ATryn is contraindicated in patients with known hypersensitivity to goat and goat-milk proteins. Allergic-type hypersensitivity reactions, including anaphylaxis, are possible. If these reactions occur during administration, the drug must be discontinued immediately and emergency treatment should be given.

The anticoagulant effect of drugs that use antithrombin to exert their anticoagulation may be altered when ATryn is added or withdrawn. To avoid excessive or insufficient anticoagulation, coagulation tests suitable for the anticoagulant used (aPTT and anti-Factor Xa activity) are to be performed regularly, at close intervals, and in particular in the first hours after the start or withdrawal of ATryn. Additionally, patients must be monitored for the occurrence of bleeding or thrombosis in such situations.

The serious adverse reaction that has been reported in clinical studies is hemorrhage (intra-abdominal, hemarthrosis, and post procedural). The most common adverse events reported in clinical trials at a frequency of ≥ 5% are hemorrhage and infusion-site reaction.

For additional details including full prescribing information, go to www.ovationpharma.com.

 

圣路易斯(MD Consult)——ATryn(一种重组抗凝血酶)的生产厂商——GTC生物治疗公司(GTC Biotherapeutics)和OVATION制药公司(OVATION Pharmaceuticals, Inc)日前宣布，ATryn已经获得美国FDA批准，用于遗传性抗凝血酶缺乏症患者以预防围手术期及围产期血栓栓塞事件。

ATryn并未获准用于遗传性抗凝血酶缺乏症患者治疗血栓栓塞事件。在美国，该药是第一个由转基因动物(山羊)生产的治疗性蛋白，也是第一个获得批准的重组抗凝血酶。与此同时，FDA兽医学中心还批准了GTC公司关于一种动物新药的申请。作为第一种来自于遗传学重组动物的药物，该药是目前在培养转基因动物(如可产生重组抗凝血酶的山羊)的重组技术中所必需的。

GTC公司已经授权OVATION公司在美国范围内销售ATryn。两家公司都期待ATryn能于2009年第二季度上市。

遗传性抗凝血酶缺乏症患者发生静脉血栓栓塞事件的危险很大，包括肺栓塞和深静脉血栓形成，这两种疾病可威胁患者生命，尤其在高危状态下。抗凝血酶是一种天然抗凝剂，在预防血栓形成过程中发挥了重要的作用。纯化的重组抗凝血酶与从人血浆中分离所得抗凝血酶具有同样的氨基酸序列。

ATryn的研发旨在提供一种安全而性能稳定的重组抗凝血酶。

“在FDA批准ATryn之后，我们可以肯定，遗传性抗凝血酶缺乏症患者的迫切治疗需要可以得到满足，”OVATION公司总裁暨首席执行官(CEO)Jeffrey S. Aronin说。

在美国、欧洲和加拿大等地区有血栓栓塞事件病史的遗传性抗凝血酶缺乏症患者中进行的临床研究，已经证实了ATryn的安全性和疗效。这些研究显示，ATryn可以预防临床显性的血栓栓塞事件的形成。至于重复给药后的安全性和免疫原性问题，将在上市后进行研究来评估。

普通人群中的遗传性抗凝血酶缺乏症患病率为1/5,000～1/2,000。有研究显示，50%的患者在25岁之前会发生一次血栓形成事件，而多达85%的患者在50岁之前会发生一次血栓栓塞事件。

ATryn是全球范围内第一个获得批准的重组抗凝血酶制剂，也是欧盟通过集中审批程序批准的第一个抗凝血酶制剂。现在，ATryn又成为第一个获得FDA批准的重组抗凝血酶制剂。

ATryn治疗的禁忌人群为已知对山羊及山羊奶的蛋白有超敏反应的患者。这类人群可能会发生包括过敏反应在内的变态反应型超敏反应。如果在给药期间出现这些反应，那么必须立刻停药，并应给予紧急治疗。

当加用或停用ATryn时，那些通过抗凝血酶途径发挥抗凝作用的药物的抗凝效果可能会发生改变。为防止抗凝过度或不足，应定期(短间隔、高频率)进行凝血试验，尤其是在开始使用和停用ATryn后的第一个小时内。此外，还应监测患者的出血或血栓形成情况。

临床试验中报告的ATryn的严重不良反应为出血(腹腔内出血、关节内出血以及术后出血)。临床试验中报告最常见的不良事件(发生率≥5%)包括出血和注射部位反应。

包括完整处方在内的更多详细资料，请参阅下列网址：www.ovationpharma.com

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