New indications for Arixtra® in the United States: the treatment of acute deep venous thrombosis and acute pulmonary emb

New indications for Arixtra® in the United States: the treatment of acute deep venous thrombosis and acute pulmonary embolism. Paris, June 4, 2004 Sanofi-Synthelabo announced today that the synthetic, selective factor Xa inhibitor Arixtra® (fondaparinux sodium) has been approved by the US Food and Drug Administration (FDA) for two new indications: · the treatment of acute deep venous thrombosis when administered in conjunction with warfarin sodium, and · the treatment of acute pulmonary embolism when administered in conjunction with warfarin sodium when initial therapy is administered in the hospital Arixtra® is already indicated in the United-States for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing hip fracture surgery, including extended prophylaxis, hip replacement surgery and knee replacement surgery. The file for the new indications for Arixtra® was submitted to the FDA July 31, 2003. The clinical dossier was based upon the findings of the MATISSE PE and MATISSE DVT studies which demonstrated that a new strength of Arixtra® 7.5 mg* given as a once daily subcutaneous injection, when administered in conjunction with warfarin sodium, can effectively and safely treat the acute phases of both deep vein thrombosis and pulmonary embolism. Arixtra® is the first antithrombotic agent to be registered in the US specifically for the treatment of acute PE since the introduction of unfractionated heparin (UFH). The MATISSE PE study is the largest worldwide trial ever performed in the treatment of pulmonary embolism. This open label trial involved 2,213 patients with symptomatic PE enrolled in 214 centres in 20 countries worldwide, including 67 centres in the US. The study showed that a fixed once daily subcutaneous dose of Arixtra® 7.5mg*, without need for coagulation monitoring, appears to be at least as effective and as safe as continuous intravenous and dose-adjusted UFH. Moreover, in the study, 15% of patients, (26.4% in the US**), received Arixtra® on an outpatient basis, after receiving the first dose in the hospital, compared to none with UFH. The MATISSE DVT trial involved 2,205 patients in 23 countries in a total of 154 centers around the world with symptomatic DVT without symptomatic PE. The study showed that Arixtra® 7.5mg*, given once daily in a fixed subcutaneous dose appears to be at least as effective and safe as dose-adjusted low molecular weight heparin (LMWH) administered subcutaneously twice a day. DVT and PE represent two manifestations of the same disease known as Venous Thromboembolism (VTE), a condition in which blood clots in the lower limbs (DVT) may travel to the lungs where they can cause a PE. VTE is the third most common cardiovascular disease after heart attack and stroke. VTE affects about two million Americans annually, at least 60,000 of whom will die of PE. VTE represents an annual cost of at least $2.9 billion in the US alone. As with other antithrombotics, the most common side effect during Arixtra® administration is bleeding. Arixtra® is contraindicated in patients with severely impaired kidney function. Arixtra® prophylactic therapy is contraindicated in patients who weigh less than 50 kg (110 pounds), undergoing hip fracture, hip replacement and knee replacement surgery because they may have an increased risk for major bleeding. Patients greater than 75 years of age also may be more likely to experience major bleeding complications. As with other antithrombotics, labeling for Arixtra® includes a Boxed Warning regarding possible spinal/epidural haematomas when spinal anaesthesia or spinal puncture is used. Arixtra® was launched in the United States on February 8, 2002, and in Europe as from March 27, 2002. On April 13, 2004, Sanofi-Synthelabo signed an agreement with GlaxoSmithKline Group (GSK) regarding the divestment by Sanofi-Synthélabo, on a worldwide basis, of Arixtra®, Fraxiparine® and related assets including the manufacturing facility located in Notre-Dame de Bondeville, France. The deal is conditional on completion of Sanofi-Synthelabo's offer for Aventis. *5mg in patients with a body weight <50kg; 10mg in patients with a body weight >100 kg **data on file In accordance with article 7 of the COB rule no. 2002-04, this press release was transmitted to the Autorité des marchés financiers (AMF) before its publication. Forward-Looking Statements This press release contains statements that constitute forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Forward-Looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words "expect," "anticipates," "believes," "intends," "estimates" and similar expressions. Although Sanofi-Synthélabo's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi-Synthélabo, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. The following factors, among other risks and uncertainties that are described in our Form 20-F as filed with the SEC on April 2, 2004 and in the Reference Document filed with the French Autorité des Marchés Financiers on April 2, 2004, could cause actual results to differ materially from those described in the forward-looking statements: the ability of Sanofi-Synthélabo to expand its presence profitably in the United States; the success of Sanofi-Synthélabo's research and development programs; the ability of Sanofi-Synthélabo to protect its intellectual property rights; and the risks associated with reimbursement of health care costs and pricing reforms, particularly in the United States and Europe. Other than as requested by applicable law, Sanofi-Synthélabo does not undertake any obligation to provide updates or to revise any forward-looking statements. Important Information: In connection with the proposed acquisition of Aventis, Sanofi-Synthélabo has filed a registration statement on Form F-4 (File no. 333-112314), including a prospectus and a prospectus supplement relating to the revised offer, and will file additional documents with the SEC. Investors are urged to read the registration statement, including the prospectus and the prospectus supplement relating to the revised offer, and any other relevant documents filed with the SEC, including all amendments and supplements, because they contain important information. Free copies of the registration statement, as well as other relevant documents filed with the SEC, may be obtained at the SEC's web site at www.sec.gov. The prospectus and the prospectus supplement relating to the revised offer and other transaction-related documents are being mailed to Aventis security holders eligible to participate in the U.S. offer and additional copies may be obtained for free from MacKenzie Partners, Inc., the information agent for the U.S. offer, at the following address: 105, Madison Avenue, New York, New York 10016; telephone: 1-(212) 929-5500 (call collect) or 1-(800) 322-2885 (toll-free call); e-mail proxy@mackenziepartners.com. In France, holders of Aventis securities are requested, with respect to the offer, to refer to the prospectus supplement (note d'information complémentaire), which has been granted visa number 04-384 by the Autorité des marchés financiers ("AMF") and which is available on the website of the AMF (www.amf-france.org) and without cost from: BNP Paribas Securities Services, GIS-Emetteurs, Service Logistique, Les Collines de l'Arche, 75450 Paris Cedex 9 and to the recommendation statement (note d'information en réponse) which has been granted visa number 04-510. The public offer to holders of Aventis ordinary shares located in Germany (the "German Offer") is being made in accordance with applicable German law and pursuant to an offer document/sales prospectus, which is available free of charge at BNP Paribas Securities Services, Grüneburgweg 14, D-60322 Frankfurt am Main (Fax: 069 - 152 05 277) and on the website of the Company (www.sanofi-synthelabo.com). Any decision to tender Aventis ordinary shares in exchange for Sanofi-Synthélabo ordinary shares under the German Offer must be taken exclusively with regard to the terms and conditions of the German Offer, as well as with regard to the information included in the offer document/sales prospectus, including any amendments thereto, issued in Germany. The French Offer, the U.S. Offer and the German Offer are being made on substantially the same terms and completion of these offers is subject to the same conditions. It is intended that the three offers will expire at the same time. Investors and security holders may obtain a free copy of the Form 20-F filed with the SEC on April 2, 2004 and any other documents filed by Sanofi-Synthélabo with the SEC at www.sec.gov as well as of the Reference Document filed with the AMF on April 2, 2004 (N° 04-0391) at www.amf-france.org or directly from Sanofi-Synthélabo on our web site at: www.sanofi-synthelabo.com. ------------------------------------------------------------ Ytterligere informasjon kan hentes på følgende hjemmeside: http://www.waymaker.no Nedenstående filer kan lastes ned: http://www.waymaker.net/bitonline/2004/06/07/20040607BIT20050/wkr0006.pdf Pressemeldingen, pdf-versjon.