Exanta

AstraZeneca PLC 02 April 2003 NEW STUDY DEMONSTRATES THE POTENTIAL OF EXANTATM (ximelagatran) FOR PREVENTION OF STROKE IN ATRIAL FIBRILLATION AstraZeneca today announced results from the first phase III stroke prevention data for ExantaTM (ximelagatran), the first of a new class of oral direct thrombin inhibitors (Oral DTI), presented at the 52nd Scientific Session of the American College of Cardiology (ACC), Chicago. The results show that fixed dose twice daily 36mg oral Exanta compares favourably with dose-adjusted warfarin in preventing stroke and systemic embolic events (SEE) in patients with atrial fibrillation (AF), meeting the study's primary efficacy endpoint. SPORTIF III*, a multi-national, randomised, open-label, parallel-group study with blinded event assessment, was designed as a non-inferiority** study to compare oral Exanta with the current standard treatment, dose-adjusted warfarin. While the study was not aimed at demonstrating superiority, the incidence of stroke and SEE seen for Exanta compared with a well-controlled warfarin treatment (average study INR 2.5) was numerically lower (40 Exanta vs 56 warfarin) in the whole population (ITT - including those who stopped treatment). Furthermore, a statistically significant relative risk reduction (RRR) of 41% (p =0.018) was demonstrated for Exanta compared with well-controlled warfarin in patients who remained on treatment for the duration of the study (OT population). These promising efficacy results need to be considered alongside the safety profile for Exanta emerging from this study and from other ongoing clinical trials, which will define its overall benefit-risk profile. In SPORTIF III, the incidence of liver enzyme (ALT) elevations was 6.5% for Exanta and mostly occurred within the first six months of treatment. These elevations were associated with no specific clinical symptoms and decreased with treatment continuation or discontinuation. With regard to bleeding and recognising that Exanta was used in a fixed dose regimen without coagulation monitoring, the combined rate of major and minor bleeding events was found to be significantly lower for Exanta than warfarin (475 vs 554 events; p=0.007) and there was no significant difference in all cause mortality between the Exanta and warfarin groups. 'Today's results confirm the potential of Exanta in stroke prevention for AF patients and highlight the important practical advantages that this unique first-in-class treatment holds over the traditional, standard treatment,' says Dr. Hamish Cameron, Vice President, Head of Exanta, AstraZeneca. 'These data, together with the results of SPORTIF V and other important studies, will form the basis for the FDA and EU submissions for Exanta in this indication, which are on track for the fourth quarter this year.' SPORTIF is the largest clinical study programme ever undertaken in the prevention of stroke in atrial fibrillation. The SPORTIF III study will be complemented later this year by the North American SPORTIF V study, which only differs to SPORTIF III in that it is a double-blind study. Exanta is currently under review 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. A regulatory submission for the treatment of VTE is also scheduled to be submitted in Europe in the fourth quarter of this year, following the outcome of studies in this indication. Stroke is the third leading cause of death in adults worldwide, with five million fatal events per year. Atrial fibrillation has been found to increase the risk of stroke fivefold, yet less than half of eligible patients receive effective treatment. This unmet need may be attributed to the limitations of the current standard treatment, warfarin, which requires regular coagulation monitoring, dose titration and has several food and drug interactions. The current worldwide market for antithrombotics is $9.6 billion. Exanta is the first of a new class of oral anticoagulants called oral DTIs. The drug is currently under phase III investigation and is the first oral anticoagulant to reach late clinical development in more than 50 years - since the development of warfarin. Exanta is a trademark of the AstraZeneca group of companies. - Ends - April 2, 2003 Media Inquiries: Steve Brown, +44 (0) 207 304 5033 Emily Denney, +44 (0) 207 304 5034 Investor Inquiries: Mina Blair-Robinson, +44 (0) 207 304 5084 Jonathan Hunt, +44 (0) 207 304 5087 Editors' Notes: *SPORTIF : Stroke Prevention by ORal Thrombin Inhibitor in atrial Fibrillation. SPORTIF III involves 3407 patients from 259 centres in 23 countries across Europe, Australia and Asia. 36mg fixed dose oral Exanta twice daily was compared with dose-adjusted warfarin (INR 2.0-3.0) once daily. Patients in the study had Non-valvular atrial fibrillation (AF) and at least one additional risk factor for stroke, which included: previous cerebral ischaemic attack; previous systemic embolism; hypertension; left ventricular dysfunction; age (3) 75 years; age (3) 65 years and coronary artery disease; age (3) 65 years and diabetes mellitus. Patients were treated for an average of 17 months in SPORTIF III. ** The rationale for 'non-inferiority' studies: As many highly effective treatments are now available in various therapeutic areas, placebo-controlled trials are often now considered unethical. Therefore, the concept of non-inferiority testing is now increasingly common where 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 predictability and convenience. Abstracts will be available online at www.acc.org and once these data have been presented media materials will be available on www.astrazenecapressoffice.com This information is provided by RNS The company news service from the London Stock Exchange

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