ASTRAZENECA’S NEW ORAL DIRECT THROMBIN INHIBITOR EXANTA™ SUPERIOR IN REDUCING RISK OF VENOUS THROMBOEMBOLISM (VTE) FOLLOWING TOTAL HIP OR KNEE REPLACEMENT SURGERY

“These results confirm the efficacy and potential benefits of treatment with ‘Exanta’,” said Hamish Cameron, Vice President and Head of Cardiovascular Therapy Area, AstraZeneca. ” ‘Exanta’ offers significant advantages over alternative products in the anticoagulant market and, once approved, will strengthen an already outstanding AstraZeneca cardiovascular portfolio. We see these results as a key step in obtaining approval for a series of indications for this innovative new class of drug.”

Results showed a significant 63 per cent relative risk reduction (2.3% vs 6.3%: p=0.0000018) in major venous thromboembolism (VTE) (proximal deep vein thrombosis (DVT) and pulmonary embolism (PE)) when treated with ‘Exanta’, compared to standard prophylaxis with enoxaparin (40mg od). A relative risk reduction in major VTE of 67 per cent (1.8% vs 5.5%) was noted for total hip replacement and a 60 per cent relative risk reduction (3.3% vs 8.2%) for total knee replacement surgery. Additionally, there was a 24 per cent (20.3% vs 26.6%) reduction in the risk of total VTE (proximal and distal DVT and PE) following prophylactic treatment (thromboprophylaxis) with ‘Exanta’, compared to enoxaparin.

The ‘Exanta’ treatment regimen in EXPRESS shows a good balance between efficacy and safety. A small increase in surgery-related bleeding was observed compared to enoxaparin, although importantly, there were no differences between treatments in clinically important bleeding events (defined as fatal, critical organ or requiring re-operation).

Between 45-57 per cent of patients undergoing total hip replacement without thromboprophylaxis develop DVT (deep vein thrombosis), a potentially fatal condition. Similarly, the rate of DVT for patients undergoing total knee replacement is 40-84 per cent. The market for anticoagulants is currently valued at $3.1 billion.

‘Exanta’ is the first Oral DTI to be submitted for regulatory approval and works by inhibiting thrombin, a key enzyme involved in the blood clotting (coagulation) process. AstraZeneca submitted a filing for a European licence for ‘Exanta’ (ximelagatran / melagatran) for the prevention of VTE following major orthopaedic surgery in July 2002. This was the first regulatory submission for ‘Exanta’. In the United States, the parallel phase III clinical trial programme in orthopaedic surgery, EXULT, remains on track.

Fifteen additional abstracts presented at the ICT highlighted the potential of ‘Exanta’ to meet a clear unmet medical need in the prevention and treatment of thromboembolism and demonstrated its benefit in terms of efficacy, safety, predictable pharmacokinetic results and tolerability across a wide patient population.

Thrombosis is one of the largest causes of morbidity and mortality in the Western world. There are nearly four million events of thromboembolic disease (including stroke, deep vein thrombosis/pulmonary embolism and myocardial infarction) each year throughout the EU and Japan.

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of ethical (prescription) pharmaceuticals and the supply of healthcare services. It is one of the top five pharmaceutical companies in the world with healthcare sales of over $16.4 billion and leading positions in sales of gastrointestinal, oncology, anaesthesia including pain management, cardiovascular, central nervous system (CNS) and respiratory products.

October 28, 2002

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