Arixtra(R) has comparable efficacy to Lovenox(R)/Clexane(R) with less major bleeding in patients with acute coronary syndromes

Main Category: Cardiovascular / Cardiology
Article Date: 06 Sep 2005 - 6:00 PDT

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GlaxoSmithKline plc announced headline results from the largest clinical trial ever conducted in patients with acute coronary syndromes (ACS), which compared its anti-thrombotic product, ARIXTRA(R) (fondaparinux sodium) with the commonly used LOVENOX(R)/CLEXANE(R) (enoxaparin)*. ARIXTRA was as effective as LOVENOX/CLEXANE for the primary composite endpoint of preventing death, myocardial infarction, and refractory ischaemia at 9 days (incidence of 5.9% and 5.8%, respectively); patients in the study experienced at least one of the three components of the primary endpoint. Furthermore, ARIXTRA was associated with a 47% (p< 0.001) reduction in major bleeding vs. LOVENOX/CLEXANE (2.1% and 4.0% incidence, respectively) in this study.1

In addition, mortality rates at one month were 2.9%in the ARIXTRA group and 3.5%in the LOVENOX/CLEXANE group, representing a 17% reduction (p=0.0219) in favour of ARIXTRA. This reduction in mortality rates was maintained at six months post therapy (5.8%in the ARIXTRA group and6.6%in the LOVENOX/CLEXANE group), representing an 11% reduction (p= 0.0373) in mortality. 1 Organization to Assess Strategies for Ischaemic Syndromes (OASIS 5), a landmark head-to-head trial, evaluated more than 20,000 patients with ACS, and was presented today at the European Society of Cardiology (ESC) meeting in Stockholm, Sweden.

"The OASIS 5 findings demonstrate that ARIXTRA is likely an effective anti-thrombotic drug in many patients with ACS already receiving aspirin and clopidogrel," said Dr. Salim Yusuf, principal investigator of the study, and professor of medicine, McMasterUniversityand Hamilton Heath Sciences, Ontario, Canada.

ARIXTRA is not currently approved in the EU or US for patients with Acute Coronary Syndromes.

Acute Coronary Syndromes

Unstable chest pain and acute myocardial infarction caused by inadequate blood supply to the heart muscle are part of a complex group of cardiac diseases called ACS that account for about 2.5 million hospital admissions worldwide and are a major cause of mortality and morbidity in Western countries. Approximately 3.5 million people worldwide are affected by ACS annually.2,3 People presenting with these conditions have an increased immediate and long-term risk of recurrent heart attack and cardiac death.4

Previous studies have shown that newer anti-thrombotics can substantially reduce the risk of heart attacks in patients; however, this is often accompanied by an increased risk of major bleeding.5 A need remains for effective therapies in ACS with a lower incidence of major bleeding. Bleeding rates of ARIXTRA in OASIS 5 coupled with similar efficacy to therapy with LOVENOX/CLEXANE, a low molecular weight heparin, demonstrated a strong risk:benefit profile for ARIXTRA in this study.

"Results from OASIS 5 soundly demonstrate that ARIXTRA, a trusted medicine in venous thrombosis, may offer tremendous potential clinical benefits in the treatment of Acute Coronary Syndromes," said Dr. Lawson Macartney, senior vice-president, Cardiovascular and Metabolic Medicine Development Centre, GlaxoSmithKline. "GSK is excited that this product can address an unmet medical need and we look forward to submitting these data to Regulatory Authorities worldwide for review so that we may bring the product to physicians and patients for use in ACS."

OASIS 5

The MICHELANGELO: OASIS 5 programme is an international, randomised, double-blind, controlled study that included over 20,000 patients in 576 sites across 41 countries. Patients in the study were randomised to receive ARIXTRA 2.5 mg once daily for 2 to 8 days, or LOVENOX/CLEXANE1 mg/kg twice daily for 2 to 8 days. Study medications were administered in addition to standard medical care, such as aspirin, clopidogrel, GP IIb/IIIa inhibitors and revascularisation procedures.The primary objective of the study was to evaluate whether ARIXTRA was at least as effective as LOVENOX/CLEXANEin preventing death, myocardial infarction (MI) or refractory ischaemia in the acute treatment of patients with chest pain (unstable angina)/ myocardial infarction (non-ST-segment elevation MI).

Secondary objectives included determining whether ARIXTRA was superior to LOVENOX/CLEXANEin reducing death or MI, and reducing major bleeding events up to Day 9, as well as to determine if the relative effect on the primary end point of ARIXTRA versus LOVENOX/CLEXANEwas sustained at Day 14, Day 30, Day 90 and Day 180.

"GlaxoSmithKline is firmly committed to providing potential treatments for the widest range of options in both arterial and venous thrombosis. We hope the encouraging news from OASIS 5 may provide patients, healthcare professionals and hospitals with a convenient treatment for a spectrum of thrombotic diseases," Macartney added.

ARIXTRA

ARIXTRA is the first in a new class of anti-thrombotics 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 protease in blood that facilitates blood clotting. ARIXTRA has a proven safety profile with no reported cases of heparin-induced thrombocytopenia (HIT), a common and potentially fatal side effect of heparin.

FOR EU MEDIA

ARIXTRA is approved for use in the European Union (EU) for the prevention of venous thromboembolicevents (VTE) in patients undergoing surgery for hip fracture (including extended prophylaxis), knee replacement, and hip replacement; and in acutely ill medical patients and patients undergoing abdominal surgery who are considered at high risk of thromboembolic complications. Additionally, ARIXTRA is indicated in the EU for the treatment of acute DVT and the treatment of acute PE, except in haemodynamically unstable patients who require thrombolysis or pulmonary embolectomy.

ARIXTRA was first authorised for use in the EU in March 2002 for the prevention of VTE in patients undergoing major orthopaedic surgery of the lower limbs. ARIXTRA is registered in 27 European countries and is currently marketed in 17 countries across Europe. Approximately 500,000 people worldwide have received ARIXTRA for prevention of venous thrombolic events (VTE), and for treatment of acute deep vein thrombosis (DVT) and pulmonary embolism (PE).

FOR US MEDIA:

ARIXTRA is the first selective inhibitor of Factor Xa, a protein central to the coagulation process. ARIXTRA is approved in the United States (U.S.) for the prevention of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (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

Contraindications

ARIXTRA is contraindicated in patients with severe renal impairment, patients with active major bleeding, bacterial endocarditis, and patients with hypersensitivity to fondaparinux sodium. In the United States, ARIXTRA is also contraindicated in patients weighing less than 50kg (less than 110 lbs) who are undergoing major surgery of the lower limbs and abdominal surgery.

Warnings

When epidural/spinal anaesthesia 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 haematoma, 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 haemostasis. Spinal/epidural anaesthesia should not be used concurrently with ARIXTRA for the treatment of VTE (see BOXED Warning in the 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, 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 110lbs). 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 with ARIXTRA. If the platelet count falls below 100,000/mm3, ARIXTRA should be discontinued.

About GlaxoSmithKline

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.

*LOVENOX(R)/CLEXANE(R) are the registered trademarks of Sanofi-Aventis.

1. Data on File, GlaxoSmithKline, King of Prussia, PA.

2. Acute Myocardial Infarction, Cardium Study #49, Decision Resources, March 2003.

3. Unstable Angina, Cardium Study #46, Decision Resources, August 2002.

4. Yusuf S, Flather M, Pogue J, et al. Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS (Organisation to Assess Strategies for Ischaemic Syndromes) Registry Investigators. Lancet 1998;352:507-14.

5. Reviewed in: Harrington et al. Antithrombotic Therapy for Coronary Artery Disease. CHEST 2004;
126:513S-548S.

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 2004.

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