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| 9 December 2003 | 2003-12-09T07:00:00.0000000-00:00 |
| FURTHER DATA SUPPORTS SAFETY AND EFFICACY OF ORAL DIRECT THROMBIN INHIBITOR, EXANTA™ (XIMELAGATRAN) IN PREVENTION OF VENOUS THROMBOEMBOLISM
AstraZeneca today announced further evidence to support the efficacy and safety profile of Exanta™ (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.
Media Enquiries:
Steve Brown, +44 (0) 207 304 5033
Edel McCaffrey, +44 (0) 207 304 5034
Investor Enquiries:
Mina Blair-Robinson, + 44 (0) 207 304 5084
Jonathan Hunt, +44 (0) 207 304 5087
Notes to Editors
· Exanta is a trademark of the AstraZeneca group of companies.
· EXULT B: Exanta Used to Lessen Thrombosis is a multi-centre, randomised, double-blind, double-dummy trial of 2,303 patients undergoing total knee replacement surgery. Patients were given oral 36mg fixed-dose ximelagatran initiated the morning after surgery, or warfarin (target INR 2.5; range 1.8-3.0) initiated in the evening of the day of surgery.
· EXULT A: Exanta Used to Lessen Thrombosis is a mutli-centre, randomised, double-blind, double-dummy trial of 2,301 patients undergoing total knee replacement surgery. Patients were given oral 24mg or 36mg fixed-dose twice daily ximelagatran initiated the morning after surgery or warfarin (target INR 2.5; range 1.8-3.0) initiated in the evening of the day of surgery.
· THRIVE Treatment: THRombin Inhibitor in Venous thromboEmbolism Treatment is a multi-centre, randomized, trial of 2,489 patients with acute VTE in 279 centres across 28 countries. Patients were given 36mg fixed-dose twice daily ximelagatran for six months, or 1mg/kg subcutaneous enoxaparin twice daily for a minimum of 5 days followed by warfarin with a target international normalised ratio (INR) of 2.0-3.0 for six months.
· AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of 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 $17.8 billion and leading positions in sales of gastrointestinal, oncology, cardiovascular, neuroscience and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global and European) as well as the FTSE4Good Index.
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