Healthcare Industry News: Factor Xa
News Release - March 14, 2006
ARIXTRA(R) (Fondaparinux Sodium) Reduced Risk of Death or Recurrent Heart Attack in Patients With Acute Coronary Syndromes (ST Elevation Myocardial Infarction)ATLANTA, March 14 (HSMN NewsFeed) -- GlaxoSmithKline plc (NYSE: GSK; London) announced today late-breaking clinical trial results of the OASIS 6 trial that compared its antithrombotic product ARIXTRAŽ (fondaparinux sodium) to standard therapy in acute coronary syndrome (ACS) patients with ST elevation MI (STEMI). The overall results of the study demonstrated superiority of fondaparinux to standard therapy (unfractionated heparin or placebo) in reducing risk of death or recurrent heart attack (risk reduction of 14% at day 30, p=0.008), with a significant reduction observed as early as day 9 (risk reduction of 17%, p=0.003). Furthermore, fondaparinux showed a significant reduction in all cause mortality (secondary endpoint) at day 9 (risk reduction 13%, p=0.043), which was maintained until the end of the study (risk reduction 12%, p=0.029) (1).
In OASIS 6, the incidence of severe haemorrhage at Day 9 was similar between fondaparinux and standard therapy treated patients. In addition, OASIS 6 showed that fondaparinux was associated with a significant net benefit-risk as assessed by the composite of efficacy and safety endpoints of death, recurrent MI and severe haemorrhage at all time points (at day 30 risk reduction was 14%, p=0.005) (1).
The OASIS 6 (Organization to Assess Strategies for Ischaemic Syndrome) trial evaluated more than 12,000 patients and was presented at the American College of Cardiology's (ACC) 55th Scientific Session in Atlanta, GA. OASIS 6 study results were also released online today in the Journal of the American Medical Association (JAMA). Please see http://jama.ama-assn.org/ for full manuscript.
"Results of OASIS 6 showed the benefit of fondaparinux for both morbidity and mortality and may prove to be a valuable treatment option for these ACS patients in the future," said Dr. Salim Yusuf, principal investigator of the study, and Professor of Medicine, McMaster University and Hamilton Heath Sciences, Ontario, Canada. "In addition, the bleeding incidences observed in OASIS 5 and 6, coupled with the efficacy outcomes, demonstrated that fondaparinux offered a positive net-benefit risk profile in patients across a range of ACS."
The OASIS 5 and 6 programmes studied over 32,000 patients worldwide. OASIS 6 results are broadly consistent with the large companion study OASIS 5 conducted in the acute treatment of patients with chest pain (unstable angina)/myocardial infarction (non-ST-segment elevation MI) (1,2).
Fondaparinux is not currently approved in any country for patients with ACS.
Acute Coronary Syndromes
ST-segment elevation myocardial infarction (STEMI) is one condition in the complex group of coronary 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 (3). 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 (4,5). 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 ischaemia) (5).
Approximately 3 million people worldwide are affected by ACS annually (6,7). People presenting with these conditions have an increased immediate and long-term risk of recurrent heart attack and cardiac death (8).
"GSK is very excited to see the results of OASIS 6, a large scale trial that showed the benefit of fondaparinux for patients with this type of ACS," said Dr. Lawson Macartney, Senior Vice-President, Cardiovascular and Metabolic Medicine Development Centre, GlaxoSmithKline. "We look forward to submitting these data to regulatory authorities worldwide for review so that we may bring fondaparinux to physicians and patients for use in the treatment of ACS."
The OASIS 6 programme is an international, randomised, double-blind study assessing the efficacy and safety of fondaparinux in patients with STEMI. OASIS 6 evaluated 12,092 patients in 447 sites across 41 countries (9).
Patients were randomised to receive fondaparinux 2.5mg once-daily subcutaneous injections for up to 8 days (6,036 patients) or standard therapy (UFH or placebo, 6,056 patients). Randomisation was dependent on whether there was an indication for UFH, based on investigator's judgement (9). All patients were followed for a minimum of 90 days and a maximum of 180 days (9). Most patients also received a medicine or a medical procedure to help open a blocked heart artery.
The primary objective of the study was to evaluate whether fondaparinux is superior to standard therapy (UFH or placebo) in preventing death or recurrent myocardial infarction (MI) up to day 30 in patients with STEMI. The safety profile of fondaparinux compared with standard therapy was evaluated in terms of severe haemorrhage up to day 9 (9).
Secondary objectives included the evaluation of whether fondaparinux has a beneficial effect compared to standard therapy in preventing death or recurrent MI at day 9 and whether this was sustained up to day 90 and 180, as well as to evaluate whether fondaparinux was superior to standard therapy in preventing death, recurrent MI and refractory ischaemia at all time points. Minor and major bleeding as well as adverse events were included in secondary safety endpoints (9).
Fondaparinux 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 fondaparinux please visit www.gsk.com.
FOR EU MEDIA
Fondaparinux is approved for use in the European Union (EU) for the prevention of venous thromboembolism (VTE) in patients undergoing surgery for hip fracture (including extended prophylaxis), major knee surgery, and hip replacement; and in acutely ill medical patients who are immobilised and patients undergoing abdominal surgery who are considered at high risk of thromboembolic complications. Additionally, fondaparinux is indicated in the EU for the treatment of acute DVT and the treatment of acute PE, except in haemodynamically unstable patients or patients who require thrombolysis or pulmonary embolectomy.
Fondaparinux 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. Fondaparinux is registered in 27 European countries and is currently marketed in 16 countries across Europe. Approximately 500,000 people worldwide have received fondaparinux for prevention of VTE, and for treatment of acute deep vein thrombosis and pulmonary embolism.
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 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 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 during a treatment with ARIXTRA and if the platelet count falls below 100,000/mm (3), 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 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.
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US Analyst/Investor enquiries:
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1. Late-breaking clinical data: The Impact of Fondaparinux, a Synthetic Factor Xa Inhibitor on Mortality and Reinfarction in Patients with Acute ST Segment Elevation Myocardial Infarction: Results of the Michelangelo-OASIS 6 Trial. American College of Cardiology, 14 March 2006.
2. Efficacy and safety of fondaparinux compared to enoxaparin in 20,078 patients with acute coronary syndromes without ST segment elevation. The OASIS (Organisation to Assess Strategies in Acute Ischaemic Syndromes)-5 Investigators. N Engl J Med. 2006; In Press
3. Acute Coronary Syndrome: Unstable Angina and Non-ST Segment Elevation Myocardial Infarction. British Medical Journal, 7 June 2003; 326:1259-1261.
4. Diagnosis of Acute Coronary Syndrome. American Family Physician, 1 July 2005, Volume 72, Number 1.
5. New Guidelines Emphasize Need for Speed When Chest Pain Strikes. American Heart Association Journal Report, 14 June 2004.
6. Acute MI, Cardium Study #49, Decision Resources, March 2003. 7. Acute Coronary Syndrome: NSTEMI, Cardium Study #2, Decision Resources, July 2005.
8. 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
9. The Michelangelo Studies: OASIS 6 (STEMI). Population Health Research Institute. (http://www.ccc.mcmaster.ca/oasis6/index.html).
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