Healthcare Industry News: Factor Xa
News Release - February 13, 2006
Pivotal Study Published in British Medical Journal Reports: ARIXTRA(R) Was Effective and Well Tolerated in Acutely Ill Medical Patients - Treatment Reduced Risk of Venous ThromboEmbolism (VTE)LONDON and PHILADELPHIA, Feb. 13 (HSMN NewsFeed) -- Results from the ARTEMIS study of ARIXTRAŽ (fondaparinux sodium) demonstrated that treatment with the antithrombotic reduced patients' risk of overall VTE by nearly half (46.7%), with no increased risk of major bleeds compared with placebo. The ARTEMIS study (ARixtraŽ for ThromboEmbolism prevention in a Medical Indications Study), was published in the 11 February issue of the British Medical Journal and evaluated the overall efficacy and safety of ARIXTRAŽ in older acutely medically ill patients.(1)
"VTE presents a significant risk to this patient population, however we have had limited understanding of the effectiveness of clot prevention to address VTE in this group," said Alexander Cohen MD, Honorary Consultant Vascular Physician, King's College Hospital, London and Chairman of the Steering Committee of the ARTEMIS study. "These results show that ARIXTRAŽ is an effective and well tolerated treatment that can reduce the risk of VTE for these patients, further helping us to define the role of antithrombotics in this setting."
VTE in the Acutely Ill
VTE refers to a common disease state comprising deep vein thrombosis (DVT) and pulmonary embolism (PE). It is a major cause of morbidity and death among hospitalized patients.(2)
VTE is a potential risk for many acutely ill medical patients admitted to the hospital. Acutely ill medical patients may be those with congestive heart failure, respiratory illness, and infectious or inflammatory disease.(1) Each of these acute medical conditions are strong independent risk factors for VTE, and may also cause prolonged immobilization, another risk factor for VTE.(3-5)
Each year an increased number of patients are admitted to the hospital for acute medical illnesses and the number of VTE cases is expected to increase.(6) Hospitalization for an acute medical illness is itself independently associated with an increased relative risk of VTE.(7)
"Results from ARTEMIS show no increased risk of major bleeding in acutely ill medical patients and support the growing body of evidence demonstrating the efficacy of ARIXTRAŽ in venous thrombosis, " said Dr. Lawson Macartney, senior vice-president, Cardiovascular and Metabolic Medicine Development Centre, GlaxoSmithKline. "GSK is excited about these results that support ARIXTRAŽ in the treatment of this population, and may help to expand the application of ARIXTRAŽ in clinical practice."
ARTEMIS is a double blind, randomized, placebo-controlled trial that included 849 patients in 35 sites across 8 countries. Patients were at least 60 years old and were admitted to hospital for congestive heart failure (class III/IV, NYHA), acute respiratory illness (in the presence of chronic lung disease) or acute infections or inflammatory disease. Patients were expected to remain in bed for at least four days.(1)
Patients were randomized to receive ARIXTRAŽ 2.5 mg or placebo once daily subcutaneous injections for 6 to 14 days. Study treatment began within 48 hours of admission. Treatment lasted for a median of 7 days (range 1-15 days) in the fondaparinux group and 7 days (range 1-13 days) in the placebo group. A total of 644 patients (75.9%) were evaluable for the primary efficacy analysis. Baseline characteristics were similar between the two groups.(1)
The primary efficacy outcome was DVT detected by routine bilateral venography along with symptomatic DVT and fatal and non fatal PE up to day 15. Results showed that VTE was detected in 5.6% (18/321) of patients treated with ARIXTRAŽ versus 10.5% (34/323) of patients on placebo, demonstrating a significant reduction in relative risk (46.7%; p=0.029).(1)
Safety outcomes were bleeding and death. Major bleeding occurred in one patient (0.2%) in each group and minor bleeds were observed in 11 patients (2.6%) in the fondaparinux group and four (1.0%) in the placebo group. No patients in the fondaparinux group and five in the placebo group had fatal pulmonary embolism (P = 0.029).(1)
ARIXTRAŽ is the first in a new 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 protease in blood that facilitates blood clotting. Heparin- induced thrombocytopenia (HIT) is not an expected side effect of ARIXTRAŽ as no causal relationship has been demonstrated to date. HIT is a potentially fatal side effect of heparins. For more information about ARIXTRAŽ, please visit http://www.arixtra.com
ARIXTRA is not currently approved in the US for acutely medically ill patients.
FOR EU MEDIA
ARIXTRAŽ is approved for use in the European Union (EU) for the prevention of VTE in patients undergoing surgery for hip fracture (including extended prophylaxis), knee replacement, and hip replacement; and in acutely ill medical patients who are immobilized and patients undergoing abdominal surgery who are considered at high risk of thromboembolic complications. Additionally, ARIXTRAŽ 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.
ARIXTRAŽ was first authorized for use in the EU in March 2002 for the prevention of VTE in patients undergoing major orthopedic surgery of the lower limbs. ARIXTRAŽ is registered in 27 European countries and is currently marketed in 16 countries across Europe. Approximately 500,000 people worldwide have received ARIXTRAŽ for prevention of VTE, and for treatment of acute deep vein thrombosis and pulmonary embolism.
FOR US MEDIA
ARIXTRAŽ is the first selective inhibitor of Factor Xa, a protein central to the coagulation process. ARIXTRAŽ 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, ARIXTRAŽ 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
ARIXTRAŽ 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, ARIXTRAŽ 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.
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 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 anesthesia should not be used concurrently with ARIXTRAŽ for the treatment of VTE (see BOXED Warning in the US Prescribing Information).
ARIXTRAŽ is not intended for intramuscular administration.
ARIXTRAŽ 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, ARIXTRAŽ should be used with caution in those patients weighing less than 50kg (less than 110lbs). ARIXTRAŽ should not be co-administered with drugs that may increase the risk of bleeding.
The efficacy and safety of ARIXTRAŽ in patients with heparin induced thrombocytopenia type II has not been studied. Thrombocytopenia can occur with ARIXTRAŽ. If the platelet count falls below 100,000/mm3, ARIXTRAŽ should be discontinued.
GlaxoSmithKline (NYSE: GSK; London) 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 2004.
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1. BMJ, doi: 10.1136/bmj.38733.466748.7C (published 26 January 2006).
2. Deep-Vein Thrombosis: Advancing Awareness to Protect Patient Lives. White Paper, American Public Health Association, 26 February 2003.
3. THRIFT Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. BMJ. 1992; 305: 567-574.
4. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest. 2001; 119 (suppl 1): 132S-175S.
5. Kearon C. Epidemiology of venous thromboembolism. Semin Vasc Med. 2001; 1: 7-25.
6. Heit JA, Silverstein MD, Mohr DN, et al. The epidemiology of venous thromboembolism in the community. Thromb Haemost. 2001; 86: 452-463.
7. Heit J, O'Fallon W, Petterson T, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population- based study. Arch Intern Med 2002;162:1245-1248.
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