Bayer HealthCare (BHC) today presented promising safety and efficacy results from two large randomized phase II studies for a novel, oral, direct Factor Xa inhibitor (BAY 59-7939) for prevention of venous thromboembolism (VTE). The data were presented at the XXth Congress of the "International Society on Thrombosis & Haemostasis" (ISTH) in Sydney, Australia. Based on these positive data, Bayer HealthCare will begin preparation of phase III clinical program in the fourth quarter of this year.

The two prospective dose-finding studies included more than 1,300 patients and demonstrated safety and efficacy for BAY 59-7939 similar to enoxaparin, a low molecular weight heparin, in preventing the incidence of venous thromboembolism in patients undergoing either knee or hip replacement surgery. In contrast to the current

gold standard enoxaparin which must be given subcutaneously, BAY 59-7939 has the advantage that it can be administered orally. In both studies, BAY 59-7939 was given twice daily in tablet form. At the moment, additional studies are investigating the efficacy and safety of administering BAY 59-7939 to patients once a day.

"The results are extremely encouraging for patients and for Bayer HealthCare. Therefore, we are planning to initiate our phase III program before the year’s end. We feel confident that we will be able to offer a safe and effective thrombosis prophylaxis that may be taken orally thus providing greater flexibility for patients," said Wolfgang Plischke, President of Bayer HealthCare’s Pharmaceuticals Division.

Safety and efficacy of BAY 59-7939 was shown across a wide dose range of 2.5-10 mg given twice daily in the studies. BAY 59-7939 achieved the endpoints of both studies, which aimed to evaluate optimal dosing for future clinical studies. In terms of post-operative bleeding frequency, there were no differences between the subcutaneously injected enoxaparin and the orally administered BAY 59-7939 over this dose range.

"BAY 59-7939 is a novel compound that appears to be effective, is well tolerated, and was comparable to the gold standard enoxaparin in this dose-finding study. I expect BAY 59-7939 to play a meaningful role in the further development of antithrombotic therapy," said Alexander G.G. Turpie, Professor of Medicine at McMaster University in Hamilton, Ontario, Canada, and Principal Investigator of the trial featuring total knee replacement surgery.

Further Clinical Development of BAY 59-7939
BAY 59-7939 is being developed, in parallel, in three key indications: VTE prevention after major orthopaedic surgery, VTE treatment and stroke prevention in atrial fibrillation.

BHC is planning to initiate phase III clinical studies for the prevention of VTE after major orthopaedic surgery in the fourth quarter of 2005. A further ongoing phase Iib study – similar to those already reported – is being performed to assess the safety and efficacy of a once-daily dosing regimen of BAY 59-7939 for VTE prevention after elective total hip replacement surgery. Taken together the combined findings of the phase II studies will drive the decision on the dosing regimen to be used in the phase III program. The company currently plans to apply for approval for this indication by the end of 2007.

A phase II dose-finding program with twice- and once-daily dosing for VTE treatment and stroke prevention in atrial fibrillation is ongoing. Based on current plans filing for market authorization in these indications is anticipated in 2009.

Liver Monitoring
With regard to liver safety, at present, no findings suggest that liver monitoring might be necessary. Close monitoring of the effects of BAY 59-7939 on the liver will be undertaken throughout the clinical development program to ensure that there is sufficient data for the authorities to establish that BAY 59-7939 does not require liver monitoring.