Exanta

AstraZeneca PLC
14 July 2003



ExantaTM (ximelagatran) shows efficacy in first study for treatment of venous
thromboembolism (VTE) - SUPPORTS REGULATORY SUBMISSION



AstraZeneca announced today that data from the THRIVE Treatment study show that
ExantaTM (ximelagatran), the first in a new class of oral anticoagulants called
oral direct thrombin inhibitors (oral DTIs), is as effective as the current
standard of care treatment regimen, enoxaparin/warfarin, in the treatment of
acute venous thromboembolism (VTE; deep vein thrombosis with or without
pulmonary embolism) and secondary prevention of recurrent VTE events.
Importantly, the six month long study, presented today at the XIX Congress of
the International Society on Thrombosis and Haemostasis (ISTH) in Birmingham,
UK, also showed a favourable trend for Exanta in bleeding and mortality rates
compared with the standard therapy regimen.



THRIVE Treatment, an international, randomised, multicentre, double-blind study,
was designed as a non-inferiority study to compare fixed dose oral Exanta 36mg
twice daily with the current standard treatment, enoxaparin (1mg/kg) followed by
dose-adjusted warfarin (INR 2.0-3.0).  The primary endpoint of the study was
achieved, demonstrating the equivalent efficacy of oral Exanta to the standard
treatment regimen in the prevention of recurrent VTE over six months. The
incidence of recurrent VTE events was 26 Exanta vs 24 enoxaparin/warfarin
(estimated cumulative risk 2.1% vs 2.0%), in the ITT (Intention To Treat)
analysis.



'The impact of thrombosis is often underestimated, despite the fact that it is
the third most common cardiovascular disease worldwide, affecting over five
million people each year,' said Dr. Hamish Cameron, Vice President, Head of
Exanta, AstraZeneca.  'The results of THRIVE Treatment complement the earlier
findings of THRIVE III, and further demonstrate the promise of Exanta to be at
least as effective as the best type of standard treatment currently available.
These studies will form the basis for the regulatory submission for Exanta in
the treatment and long-term prevention of VTE, which remains on track for late
this year.'



Safety and mortality outcomes also showed a favourable trend for Exanta over
enoxaparin/warfarin with respect to the risk of major bleeding: 14 Exanta vs 25
standard treatment, (estimated cumulative risk 1.3% vs 2.2%) in the OT (On
Treatment) analysis and all-cause mortality: 28 Exanta vs 42 standard treatment,
(estimated cumulative risk 2.3% vs 3.4%), ITT analysis.



Laboratory blood tests in the study showed an incidence of liver enzyme
elevations in 9.6% of patients receiving Exanta, compared with 2% of patients
receiving enoxaparin/warfarin. These elevations decreased spontaneously whether
treatment continued or was stopped.  As has been seen in previous studies, these
elevations were typically transient and not associated with any specific
clinical symptoms.



Patients taking Exanta benefit from at least as effective anti-thrombotic
protection as those treated with well-controlled warfarin, but without the
limitations of warfarin treatment or its requirement for time and cost-intensive
coagulation monitoring and dose titration.  These promising efficacy results
need to be considered alongside the safety profile for Exanta emerging from this
study and from other clinical trials, which will define its overall benefit-risk
profile.



Exanta has completed phase III studies in a number of indications and is the
first oral anticoagulant to reach late stage clinical trials since the
development of warfarin more than 50 years ago.  To date more than 30,000
patients have been enrolled in the Exanta clinical trial programme.  Of the
17,000 patients who have been treated with Exanta, over a third (7,000) have
received Exanta treatment for at least six months.  The current worldwide market
for anti-thrombotics is $9.6 billion.



Exanta is being reviewed in Europe for the prevention of venous thromboembolism
(VTE) following elective hip or knee replacement surgery and will be submitted
for regulatory approval in the US for the same indication in Q4 2003.  In
addition to the regulatory submission for the treatment of VTE, scheduled for
submission in Europe in the fourth quarter of this year, submissions in the EU
and US for the prevention of stroke in atrial fibrillation patients are also
planned for the 4Q of 2003.



Exanta is a trademark of the AstraZeneca group of companies.



14 July 2003




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Editors' Notes:



The THRIVE Treatment study was established from study groups from the THRIVE II
& V studies.



The THRombin Inhibitor in Venous thromboEmbolism (THRIVE) Treatment study
involved 2,489 patients with acute deep vein thrombosis (DVT), of whom 37% had
confirmed pulmonary embolism. Patients were randomly assigned to, and received,
either oral ximelagatran 36mg bid for six months, or subcutaneous enoxaparin 1mg
/kg bid for a minimum of five days followed by warfarin (target INR of 2.0-3.0)
for six months.



The rationale for 'non-inferiority' studies:  As many highly effective
treatments are available in various therapeutic areas, placebo-controlled trials
are often now considered unethical. Therefore, the concept of non-inferiority
testing is increasingly common where the objective of these studies is to
demonstrate that a treatment is 'not inferior to' or 'as effective as' a gold
standard treatment.  This can then enable treatments to be differentiated in
terms of their respective additional advantages to the patient and physician,
such as convenience or benefit-risk.  Exanta met the non-inferiority criterion
in the THRIVE Treatment study.



- Ends -




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