FIRST CHRONIC TREATMENT STUDY WITH ORAL EXANTA™ (XIMELAGATRAN) DEMONSTRATES HIGHLY SIGNIFICANT LONG TERM BENEFIT IN PREVENTING RECURRENT VENOUS THROMBOEMBOLISM (VTE)

New results from the first chronic treatment study for EXANTA™ (ximelagatran), an oral direct thrombin inhibitor (Oral DTI), presented today at the annual Meeting of the American Society of Haematology, in Philadelphia, show that EXANTA treatment for 18 months following standard six month anticoagulation treatment is highly effective in prevention of recurrent venous thromboembolism (VTE) after an initial deep vein thrombosis (DVT) and/or pulmonary embolism (PE).

Results from the THRIVE III* study demonstrate that oral EXANTA is very effective in preventing recurrence of VTE events by 84 per cent (relative risk reduction; RRR), compared to placebo (p<.0001) following standard duration treatment.

THRIVE III is a multinational, randomised, multicentre, double-blind study comparing fixed dose oral EXANTA 24mg twice daily, to placebo. The study involved 1,233 patients who had been treated for six months with current standard anticoagulation therapy after an initial VTE event prior to the 18 month treatment period with EXANTA.

Notably, these long term results demonstrate that the clinical potential for EXANTA in effective secondary prevention of thromboembolic events is achieved without an increased risk of bleeding. The data show no significant increase in total bleeding events for EXANTA compared with placebo (estimated cumulative risk: 23.9 per cent vs 21 per cent; p=0.1703; EXANTA and placebo respectively).

“Today’s exciting results from THRIVE III show that oral ximelagatran provides a convenient, well tolerated and effective solution for extending anticoagulation treatment beyond the current standard of six months’ warfarin treatment for patients having suffered DVT and/or PE,” says Dr. Henry Eriksson, THRIVE III Principle Investigator, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. “Ximelagatran represents a potential medical breakthrough in the long-term secondary prevention and treatment of venous thromboembolism and it satisfies a clear unmet medical need for long term oral anticoagulation treatment, without the need for coagulation monitoring or dosage titration.”

Current standard anticoagulation treatment regimens to prevent recurrent DVT and PE only run for a standard six months. Physicians considering longer treatment face a risk-benefit analysis for patients, balancing the desire to prevent additional VTEs, against the risk of bleeding associated with current therapeutic options, such as warfarin (vitamin K antagonists).

The THRIVE III data show an encouraging efficacy-safety profile. Increases in alanine aminotransferase (ALT) levels were observed with EXANTA compared to placebo (estimated cumulative risk of 6.4% vs 1.2%). Importantly, however, these enzyme changes occurred within the first six months of treatment, had no specific pattern of clinical symptoms and decreased with or without drug discontinuation.

The EXULT A** study, also presented at ASH, demonstrates that fixed dose oral EXANTA administered post-operatively, is superior in efficacy to warfarin for total DVT and/or PE and/or all-cause mortality (20.3 per cent, EXANTA vs 27.6 per cent, warfarin, p=0.03). Dose-adjusted warfarin or LMWH is currently viewed as the standard treatment in the USA for VTE prophylaxis following total knee replacement surgery. There were no statistically significant differences in incidence of major or any (major or minor) bleeding, perioperative indicators of bleeding, or wound drainage or appearance between the two groups in the EXULT A study.

Thrombosis is one of the largest causes of morbidity and mortality in the western world. There are nearly four million events of thromboembolic disease (including stroke, deep vein thrombosis, pulmonary embolism and myocardial infarction) each year in the EU and Japan. The markets for anticogulants is currently valued at $3.1bn a year.

EXANTA is the first oral direct thrombin inhibitor (Oral DTI) 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. A regulatory filing for EXANTA in the treatment of VTE, based on the THRIVE studies, will be submitted in Europe in 4Q 2003, and the US filing for prevention of VTE in orthopaedic surgery is scheduled for 4Q 2003 (the European filing was submitted in July, 2002).

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