Exanta

AstraZeneca PLC
08 December 2003





Further data supports safety and efficacy of oral direct thrombin inhibitor,
ExantaTM (ximelagatran) in prevention of venous thromboembolism


AstraZeneca today announced further evidence to support the strong efficacy and
safety profile of ExantaTM (ximelagatran), following a presentation at the
American Society of Haematology (ASH) Annual Meeting 2003, San Diego, US.


The EXULT B randomised, double-blind study, involving 2303 patients across five
countries, compared oral fixed dose Exanta, 36 mg, given post-operatively twice
daily, to standard anticoagulant treatment, dose adjusted warfarin, in patients
undergoing total knee replacement surgery.   Exanta was shown to provide
superior efficacy to warfarin in preventing total venous thromboembolism (VTE)
and all-cause mortality (22.5 per cent Exanta vs. 31.9 per cent warfarin, p<
0.001), with no significant difference in bleeding compared with dose-adjusted
warfarin.


Exanta is in development as the first oral treatment in a new class of direct
thrombin inhibitors (DTIs) to prevent and treat thrombosis, one of the largest
causes of morbidity and mortality in the western world. Those at greatest risk
of VTE include patients undergoing orthopaedic surgery. More than half of
patients undergoing major total hip or knee replacement currently develop VTE in
the absence of preventative anticoagulant treatment. The most frequently used
oral anticoagulant currently, warfarin, is effective, but it is limited by a
number of factors including slow onset and offset of action, frequent dose
adjustment, numerous drug and food interactions, and the need for routine
coagulation monitoring. In contrast, oral Exanta has a rapid onset of action, a
fixed dose regimen and no requirement for coagulation monitoring.



These results confirm the findings of the EXULT A study, presented at the ASH
Annual Meeting 2002, with both studies now showing that oral Exanta 36 mg twice
daily is clinically effective and superior compared to well-controlled warfarin
in reducing total VTE and all-cause mortality among patients undergoing total
knee replacement surgery, with no increase in bleeding.

The EXULT A and B studies, comparing Exanta to warfarin in around 5,000
patients, will form the basis of a FDA regulatory submission for this
indication, to be submitted by the end of 2003. The outcome of the EU regulatory
submission for Exanta for prevention of VTE in patients undergoing elective hip
or knee replacement surgery is expected shortly.  The European licence
submission includes data involving almost 7,500 patients that reflect the
typical treatment regimen in Europe, and is based on studies that compare Exanta
with the injectable low molecular weight heparin (LMWH), enoxaparin.



The ASH Annual Meeting 2003 also included a further presentation of the longer
term THRIVE Treatment study in patients with VTE and at risk of recurrent
thromboembolic events.  First presented at the International Society of
Haemostasis and Thrombosis (ISTH) in July 2003, THRIVE Treatment compares oral
fixed dose Exanta 36 mg twice daily to the current standard treatment for acute
VTE: in this study, the injectable LMWH, enoxaparin, followed by oral
dose-adjusted warfarin, was given over six months.  The study aimed to evaluate
treatment of DVT with or without PE, and prevention of further VTE events.



The THRIVE Treatment study showed oral Exanta to be as effective and well
tolerated as the standard treatment, but without limitations such as coagulation
monitoring and dose titration.  Laboratory blood tests in this long-term study
showed an incidence of transient liver enzyme elevations in 9.6 per cent of
patients receiving Exanta.  These elevations decreased spontaneously whether
treatment continued or discontinued and as has been seen in previous studies,
were not typically associated with any specific clinical symptoms.



Exanta is the first oral anticoagulant to reach late-stage clinical development
in almost 60 years, and has been the subject of the most extensive clinical
development programme to date, involving approximately 30,000 patients.  It is
currently in phase III development for the key indications of stroke prevention
in atrial fibrillation, treatment of VTE and long-term secondary prevention of
VTE, with regulatory submissions to be filed in Europe and the US by the end of
the year. The current worldwide market for antithrombotics is $9.6 billion.



8th December 2003



Media Enquiries

Steve Brown, [phone]

Edel McCaffrey, [phone]



Investor Enquiries:

Mina Blair-Robinson, [phone]

Jonathan Hunt, [phone]



-Ends-


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