Healthcare Industry News: sanofi-aventis
News Release - April 6, 2006
ARIXTRA(R) Significantly Reduced Major Bleeding Compared to LOVENOX(R) in a Study of Patients With Acute Coronary SyndromesHead-to-Head Data Published in New England Journal of Medicine Report
PHILADELPHIA, April 6 (HSMN NewsFeed) -- Data published today in the New England Journal of Medicine from OASIS 5, one of the largest clinical trials ever conducted in patients with acute coronary syndromes (ACS), demonstrated that treatment with the antithrombotic medicine, ARIXTRA® (fondaparinux sodium) significantly reduced major bleeding by nearly half (48 percent) as compared to LOVENOX®* (enoxaparin) at day 9. The results showed ARIXTRA, manufactured by GlaxoSmithKline (NYSE: GSK ), demonstrated comparable efficacy to LOVENOX at day 9.
Previous studies have shown that blood thinners can substantially reduce the risk of heart attacks in patients with ACS; however, this may be accompanied by an increased risk of major bleeding. Therefore, there is a need for effective therapies in ACS with a lower incidence of major bleeding.
"These data are very encouraging," said Dr. Salim Yusuf, principal investigator of the study and professor of medicine, McMaster University and Hamilton Health Sciences, Ontario, Canada. "This patient population needs treatments that have the benefits of standard therapies while also reducing the bleeding risk."
ARIXTRA is not approved for use in any country in patients with ACS.
About the Study: Organization to Assess Strategies for Ischemic Syndromes (OASIS) 5
The OASIS 5 program is an international, randomized, double-blind, controlled study that included more than 20,000 patients at 576 sites across 41 countries. Patients in the study were randomized to receive either ARIXTRA 2.5 mg once daily up to eight days or LOVENOX 1 mg/kg twice daily for two to eight days. Study medications were administered in addition to standard medical care, such as aspirin, clopidogrel, glycoprotein IIb/IIIa inhibitors and revascularization procedures. The primary efficacy objective of the study was to evaluate whether ARIXTRA was as effective as LOVENOX in preventing death, myocardial infarction (MI) or refractory ischemia in the acute treatment of ACS patients with unstable angina or non-ST-segment elevation MI (NSTEMI). The primary safety objective was to evaluate major bleeding events up to day 9.
Unstable angina (potentially life-threatening chest pain) and acute MI (heart attack) caused by inadequate blood supply to the heart muscle are part of a complex group of cardiac diseases called ACS. NSTEMI is a type of heart attack typically caused by a severely, but not completely, blocked heart artery.
Prespecified secondary outcomes included the following: death or myocardial infarction; death, myocardial infarction, or refractory ischemia; and the individual components of these composite outcomes at 30 days and at the end of the study.
ARIXTRA was as effective as LOVENOX for the primary composite endpoint of preventing death, myocardial infarction, and refractory ischemia (5.8 percent and 5.7 percent incidence, respectively) at nine days. ARIXTRA was also associated with a 48 percent (p<0.001) reduction in major bleeding versus LOVENOX (2.2 percent and 4.1 percent incidence, respectively) in this study. The study also showed mortality rates at one month were 2.9 percent in the patient group receiving ARIXTRA and 3.5 percent in the patient group receiving LOVENOX, representing a 17 percent reduction (p=0.02) in favor of ARIXTRA. All-cause mortality rates at six months were 5.8 percent among patients receiving ARIXTRA and 6.5 percent in the LOVENOX group (p=0.05).
"New antithrombotic therapies for patients with ACS are needed, and GSK looks forward to submitting these data to regulatory agencies worldwide for review so that we may bring this important therapy to physicians and patients," said Dr. Lawson Macartney, senior vice president, Cardiovascular and Metabolic Medicine Development Center, GlaxoSmithKline.
Acute Coronary Syndromes
ACS account for about 2.5 million hospital admissions worldwide and are a major cause of mortality and morbidity in Western countries.(1) There are three main cardiac diseases that make up ACS conditions: unstable angina or chest pain, non ST-segment elevation myocardial infarction (NSTEMI), and STEMI; the latter two are also known as heart attacks.(2,3) STEMI is a severe heart attack in which there is irreversible myocardial damage as a result of insufficient blood supply to the heart muscle (or myocardial ischemia).(3)
ARIXTRA is the first in a class of antithrombotics that selectively inhibits Factor Xa, a central protein in the coagulation process. In the treatment of thrombosis, Factor Xa plays a central role in the generation of thrombin, a protein in blood that facilitates blood clotting.
For more information about ARIXTRA, please visit http://www.gsk.com.
ARIXTRA is the first selective inhibitor of Factor Xa, a protein central to the coagulation process. ARIXTRA is approved in the United States for the prevention of VTE, which includes DVT and PE, in patients undergoing surgery for hip fracture (including extended prophylaxis), knee replacement, hip replacement, and in abdominal surgery patients who are at risk for thromboembolic complications. Additionally, ARIXTRA is indicated for the treatment of acute DVT when administered in conjunction with warfarin sodium and for the treatment of acute PE when administered in conjunction with warfarin sodium, when initial therapy is administered in the hospital.
Important Safety Information
In Europe and the United States, ARIXTRA is contraindicated in patients with severe renal impairment. In the United States, ARIXTRA is also contraindicated in patients weighing less than 50 kg (less than 110 lbs) who are undergoing major surgery of the lower limbs and abdominal surgery. ARIXTRA is contraindicated in patients with active major bleeding, bacterial endocarditis, and patients with hypersensitivity to fondaparinux sodium.
When epidural/spinal anesthesia or spinal puncture is employed, patients anticoagulated with low-molecular-weight heparins, heparinoids or fondaparinux sodium are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. The risk of these events may be higher with postoperative use of indwelling epidural catheters or concomitant use of drugs affecting hemostasis. Spinal/epidural anesthesia should not be used concurrently with ARIXTRA for the treatment of VTE (See BOXED warning in US Prescribing Information).
ARIXTRA is not intended for intramuscular administration.
ARIXTRA should be used with caution in all patient groups with increased risk of bleeding. This includes the elderly, and patients with moderate renal or severe hepatic impairment. In the EU, ARIXTRA should be used with caution in those patients weighing less than 50kg (less than 110 lbs). ARIXTRA should not be co-administered with drugs that may increase the risk of bleeding.
The efficacy and safety of ARIXTRA in patients with heparin-induced thrombocytopenia type II has not been studied. Thrombocytopenia can occur during a treatment with ARIXTRA and if the platelet count falls below 100,000/mm3, ARIXTRA should be discontinued.
GlaxoSmithKline is one of the world's leading research-based pharmaceutical and healthcare companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit http://www.gsk.com.
Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the Operating and Financial Review and Prospects in the company's Annual Report on Form 20-F for 2005.
References (1) Mehta S.R. Efficacy and safety of fondaparinux compared to enoxaparin in 20,000 high risk patients with ACS without ST elevation; the OASIS 5 Michelangelo programme. Presentation at the European Society of Cardiology, 5 September 2005 (http://www.escardio.org/knowledge/OnlineLearning/slides/ ESC_Congress_2005/Mehta-FP1332). (2) An International Randomized Double-Blind Study Evaluating the Efficacy and Safety of Fondaparinux versus Enoxaparin in the Acute Treatment of Unstable Angina / Non ST-Segment Elevation MI Acute Coronary Syndromes. Population Health Research Institute (http://www.cardio.on.ca/oasis5/). (3) ARIXTRA Prescribing Information, GlaxoSmithKline, 2005.
*LOVENOX is a registered trademark of sanofi-aventis.
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