Sanofi-aventis said the results of the TREK dose-ranging study for its new injectable anticoagulant, AVE5026, demonstrated a highly statistically significant dose response in prevention of venous thromboembolism (VTE) in patients undergoing elective total knee replacement surgery.
AVE5026 is a new Ultra Low Molecular Weight Heparin, with predominantly anti-Xa activity, administrated subcutaneously once daily. The TREK study involved 705 patients in 19 different countries. In this dose ranging study, AVE5026 was administered for up to ten days for primary prevention of VTE in patients undergoing elective total knee replacement surgery. Enoxaparin 40 mg once daily was used as the comparator.
The primary efficacy endpoint was a composite endpoint of asymptomatic and symptomatic VTE, as well as VTE related deaths. The results of the study demonstrated a highly significant dose response (p<0.0001) on the primary efficacy endpoint with event rates at 40.0 per cent, 44.1 per cent, 15.6 per cent, 13.6 per cent and 5.3 per cent for the AVE5026 doses of 5, 10, 20, 40 and 60 mg respectively. In comparison, the event rate in the enoxaparin comparator arm was 35.8 per cent. A statistically significant dose response (p=0.0231) was found for major bleedings with rates increasing from 0 per cent to 3.4 per cent for the AVE5026 dosing arms versus 0 per cent in the enoxaparin arm. A statistically significant dose response (p=0.0003) was also found for any bleeding with rates ranging from 3.8 per cent to 20.5 per cent for the AVE5026 dosing arms, compared with 5 per cent in the enoxaparin arm.
In the TREK study, compared to enoxaparin, AVE5026 20 mg and 40 mg showed a superior efficacy for confirmed adjudicated VTE (58 per cent RRR, p=0.0017 & 61 per cent RRR, p=0.0010 respectively) with a good safety profile (any bleeding rates with AVE5026 20 mg : 3,8 per cent, with AVE5026 40 mg : 7.5 per cent versus 5 per cent with enoxaparin).
"The results of the TREK study are very promising and AVE5026 has a potential to become the new gold standard injectable therapy for VTE prevention" said Michael Rud Lassen, Department of Orthopaedics, Hillerød hospital, Denmark, and Chairman of the Steering Committee of the TREK study.
A large scale phase III clinical trial program is planned to start in 2008, involving more than 10,000 patients. Clinical studies will be conducted in VTE prevention in patients undergoing orthopaedic or abdominal surgery or receiving chemotherapy, with a submission planned in 2010. A clinical study in VTE prevention in medical patients will also be run with a submission planned in 2011.
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