2009年2月9日 asahi

動物工場製品、米で承認　組み換えヤギで血液凝固防止剤

　米食品医薬品局（ＦＤＡ）は６日、ヒトの遺伝子を組み込んだ「遺伝子組み換えヤギ」の乳から作った血液凝固防止剤を承認したと 発表した。組み換え技術を使って有用物質を動物に大量に作らせる「動物工場」の開発は各国で行われているが、ＦＤＡが組み換え動物を使った製品を承認した のは初めて。

　この薬はATryn®といい、GTC Biotherapeutics （マサチューセッツ州）などが開発した。

　ヒトには、血液を固まりにくくする働きがあるアンチトロンビン（ＡＴ）と呼ばれるたんぱく質がある。このたんぱく質の設計図に当たる遺伝子を、ヤギの受精卵に組み込んだ。ヤギ乳に含まれるたんぱく質の遺伝子のところに組み込まれた受精卵を使うと、生まれたヤギは設計図に従いヒトＡＴを作る。組み換えヤギの乳の中にはヒトＡＴが高い濃度で含まれ、これを集めて精製し、薬にした。

　この薬は先天的にＡＴができない重い病気のため、手術や出産時に肺血栓などが起きやすい患者の治療に使う。

　ＦＤＡは昨年９月、動物工場や食用を想定した遺伝子組み換え動物の産業利用に道を開く指針案を公表。ＧＴＣ社のこの薬は、欧米とカナダで臨床試験 が行われ、欧州ですでに承認されていた。米国では、今年１月の指針の最終決定を受けて承認された。ＧＴＣ社は「今年４月以降に出荷する」としている。

　ＦＤＡ指針では、人体や環境への安全性の証明などが生産者に義務づけられるが、環境団体などからは懸念の声も上がっていた。

　組み換え技術はすでにトウモロコシや大豆といった作物では実用化されている。

　医薬品としては、大腸菌やハムスターの細胞に人間の血液成分などを作らせて薬にした血液凝固剤や糖尿病薬などが実用化されている。だが、菌の培養 などが必要でコストが高い。動物工場なら医薬品の大量生産が見込め、コストダウンにつながるという。日本でも研究が進んでいる。

　動物工場を増やし、生産力を高めるには最終的には体細胞クローン技術を使うと考えられている。

February 6, 2009　GTC Biotherapeutics

ATryn® (Antithrombin [Recombinant]) Approved by the FDA
Only recombinant option for patients with hereditary antithrombin deficiency, a rare and potentially life-threatening condition

GTC Biotherapeutics and OVATION Pharmaceuticals, Inc. announced today that the U.S. Food and Drug Administration (FDA) approved ATryn® (Antithrombin [Recombinant]) for the prevention of peri-operative 手術前 and peri-partum 出産前 thromboembolic 血栓塞栓症 events in hereditary antithrombin deficient アンチトロンビン欠乏症 patients. It is not indicated for treatment of thromboembolic events in hereditary antithrombin deficient patients. ATryn is the first ever transgenically produced therapeutic protein and the first recombinant antithrombin approved in the U.S. 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 U.S. ¹ 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.² Antithrombin is a natural anticoagulant that plays an important role in controlling the formation of blood clots.² Purified recombinant antithrombin has the same amino acid sequence as antithrombin derived from human plasma.³

"The approval of ATryn marks a significant milestone in the development of this innovative recombinant technology and delivers a new therapeutic option to benefit hereditary antithrombin deficient patients who are undergoing surgery or childbirth procedures," said Geoffrey F. Cox, Ph.D., GTC's Chairman and Chief Executive Officer. "Advancing this novel technology from the early days of demonstrating its capability to the daily practice of producing a safe and efficacious product for the U.S. and the European Union, is a testament to the persistence and capability of our employees."

ATryn was developed to provide a safe and consistent supply of recombinant antithrombin.³

"With FDA approval of ATryn, we can help ensure that patients with hereditary antithrombin deficiency, a rare clotting disorder associated with severe complications, have access to much needed therapy," said Jeffrey S. Aronin, OVATION President and Chief Executive Officer. "Bringing ATryn to market gives us the opportunity to make a meaningful difference in the lives of people with this rare disorder and is consistent with Ovation's mission of addressing unmet medical needs of small patient populations."

The safety and efficacy of ATryn was established in clinical studies conducted in hereditary antithrombin deficient patients with a history of thromboembolic events in the U.S., 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 repeat dosing.

The prevalence of hereditary antithrombin deficiency in the general population is approximately one in 2,000 to one in 5,000.^4,5 Half these patients may experience a thrombosis before 25 years of age⁶ and, based on a study, up to 85 percent may suffer a thromboembolic event by age 50.⁷

About ATryn
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.⁸ It is now also the first recombinant antithrombin product approved by the FDA.

Important Safety Information
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, treatment must be discontinued immediately and emergency treatment should be administered.

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 (e.g., aPTT and anti-Factor Xa activity) are to be performed regularly, at close intervals, and in particular in the first hours following 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 more information including full prescribing information go to www.ovationpharma.com.

About Transgenic Production
The process for producing ATryn involves scientists inserting DNA for the human antithrombin protein into a single-celled goat embryo. This embryo is implanted into a surrogate doe. The resulting transgenic offspring are able to produce high levels of antithrombin in their milk. This protein is collected and purified from the milk to produce ATryn, which is administered to patients by intravenous infusion.

About GTC Biotherapeutics
GTC Biotherapeutics develops, supplies, and commercializes therapeutic proteins produced through transgenic animal technology. In addition to ATryn, GTC is developing a portfolio of recombinant human plasma proteins with known therapeutic properties. These proteins include recombinant forms of human coagulation factors VIIa, VIII, and IX, which are being developed for the treatment of hemophilia, and alpha-1 antitrypsin.

GTC also has a monoclonal antibody portfolio that includes a monoclonal antibody to CD20 and a monoclonal antibody to CD137. GTC's intellectual property includes a patent in the United States through 2021 for the production of any therapeutic protein in the milk of any transgenic mammal. GTC's transgenic production platform is particularly well suited to enabling cost effective development of proteins that are difficult to express in traditional recombinant production systems as well as proteins that are required in large volumes. Additional information is available on the GTC web site, http://www.gtc-bio.com.

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the commercial launch of ATryn in the U.S. and the prospects for further clinical development of ATryn. Such forward-looking statements are subject to a number of risks, uncertainties and other factors that could cause actual results to differ materially from future results expressed or implied by such statements. Factors that may cause such differences include, but are not limited to, the risks and uncertainties discussed in GTC's most recent Annual Report on Form 10-K and its other periodic reports filed with the Securities and Exchange Commission, including the uncertainties associated with dependence upon the actions of collaboration partners and regulatory agencies.

GTC cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this document, and GTC undertakes no obligation to update or revise the statements, except as may be required by law.

About OVATION Pharmaceuticals
OVATION is a fast growing biopharmaceutical company that develops and commercializes medically necessary therapies to satisfy unmet medical needs for patients with severe illnesses. Headquartered in Deerfield, Ill., with products available in more than 85 countries, OVATION is committed to having a significant impact on patients' lives through its focus on central nervous system (CNS), hematology/oncology, and hospital-based therapies. The company expects five new launches over the next three years, fueled largely by its late-stage CNS pipeline, which is one of the most robust in the industry. OVATION has been recognized for excellence in the global pharmaceutical and biotechnology industries with the 2006 and 2007 "Pharma Company of the Year" award from Scrip magazine for small to mid-sized enterprises. More information about the company, its products and full prescribing information may be found at www.ovationpharma.com.