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Ximelagatran Study Shows Potential for Stroke Prevention

European Society of Cardiology (ESC) Congress 2003, Vienna, Austria, September 2/PRNewswire/ -- Latest data from the full presentation of the SPORTIF III(1) study shows a net clinical benefit for Exanta(TM) (ximelagatran), the first in a new class of oral direct thrombin inhibitors (oral DTIs), compared with the current standard treatment, dose-adjusted warfarin, in preventing stroke and systemic embolic events (SEE) in patients with atrial fibrillation (AF).

In an assessment of the combined rates of deaths, primary events and major bleeding while on treatment, a statistically significant 104 (4.6%) events were seen with Exanta compared with 143 (6.1%) with warfarin (p=0.022). This important finding illustrates that patients can benefit from an effective treatment to prevent morbidity and mortality, while also avoiding the limitations that are associated with currently available treatments.

The primary endpoint of SPORTIF III was met in demonstrating that fixed dose twice daily 36mg oral Exanta compares favourably with well-controlled dose-adjusted warfarin in prevention of stroke and SEE in patients with AF (40 Exanta vs 56 warfarin events, ITT population). These efficacy results were also consistently reflected across all sub-populations and secondary composite endpoints, demonstrating the potential for Exanta as an effective and convenient replacement for warfarin in this indication, particularly in light of the high level of warfarin control in the study (average INR 2.5).

"These results offer real hope for people with atrial fibrillation, who are at five times greater risk of stroke. Half of people with atrial fibrillation who are at risk of stroke go untreated due to the limitations of current therapies, such as warfarin which, although effective, requires coagulation monitoring, dose titration and dietary restrictions", comments Professor Bertil Olsson, co-lead investigator of SPORTIF III and Professor of Cardiology, University Hospital, Lund, Sweden. "Therefore, a new drug, such as ximelagatran, represents a distinct innovation in anticoagulant therapy that could fill this treatment gap and help to reduce the burden which stroke currently places on patients and health services all over the world."

SPORTIF III, a multi-national, randomised, open-label parallel-group study with blinded event assessment, involved 3407 patients from 259 centres across Europe, Australia and Asia. Patients were treated for an average of 17 months, providing important safety data to support the emerging benefit-risk profile for Exanta.

Despite no coagulation monitoring or dose titration in the Exanta group, neither stroke nor bleeding rates were increased relative to well-controlled warfarin. Furthermore, the combined rate of major and minor (total) bleedings was significantly lower for Exanta compared with warfarin (p=0.007).

Transient elevations in the levels of liver enzymes (alanine aminotransferase, ALAT) were observed in 6.3% of patients receiving Exanta and an incidence of elevated bilirubin > 2x ULN combined with ALAT > 3x ULN was seen in 0.4% of Exanta patients compared with 0.1% of warfarin patients. As in other Exanta phase III studies to date, these ALAT elevations decreased towards baseline with treatment continuation or discontinuation and were not typically associated with specific clinical symptoms. These findings are under evaluation together with all safety results from the full Exanta clinical study programme in order to establish the overall benefit-risk profile for the product.

"Data reported from SPORTIF III have underlined the overall clinical benefit and potential of Exanta in this important area of unmet medical need", comments Dr Hamish Cameron, Vice President, Head of Exanta, AstraZeneca. "The results of SPORTIF III enhance the emerging benefit-risk profile for Exanta and will be complemented by the presentation of the second major study in this indication, SPORTIF V, at the American Heart Association (AHA) meeting later this year."

Exanta is also in phase III investigation in several indications for venous thrombosis and is the first oral anticoagulant to reach late stage clinical development in 60 years since the development of warfarin. The potential of Exanta in the treatment of arterial thrombosis has also been highlighted in the phase II ESTEEM(2) study, presented at the ESC Congress 2003 yesterday. ESTEEM is the first study to evaluate an oral DTI in long-term treatment for patients at high risk of arterial disease and provides a strong foundation for possible future development for Exanta in arterial indications.

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Source: AstraZeneca

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