Bayer HealthCare AG announced the submission of a Marketing Authorization Application to the European Agency for the Evaluation of Medicinal Products (EMEA) for approval to market rivaroxaban (Xarelto) for the prevention of venous thromboembolism (VTE) after major orthopaedic surgery of the lower limbs.
Rivaroxaban is an investigational, oral, once-daily direct Factor Xa inhibitor. Data from one of the pivotal studies (RECORD3) was presented prior to the EMEA submission and revealed that rivaroxaban significantly reduces the risk of VTE in patients undergoing total knee replacement surgery compared with enoxaparin, the current standard of care therapy. Rivaroxaban is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
"The submission of the data for VTE prevention to the EMEA is an important milestone in the development of this new treatment for the prevention of life-threatening blood clots. As an effective and convenient, once-daily oral treatment with a reassuring safety profile, we feel confident that rivaroxaban has the potential to set a new standard of care in the preventative treatment of thrombosis in patients undergoing major orthopaedic surgery," said Dr. Kemal Malik, Head, Global Development and member, Bayer HealthCare Executive Committee.
VTE is a type of thromboembolic disease that is caused by the obstruction of a blood vessel by a blood clot. In the EU it is estimated that there are 543,000 deaths due to VTE each year. People undergoing major surgery, in particular total knee or hip replacement, are prone to developing VTE due to a combination of factors such as prolonged bed rest, damage to blood vessels and an increased tendency of the blood to clot. It is estimated that up to 50 per cent of patients undergoing lower limb surgery develop VTE if they do not receive preventative care.
The Marketing Authorization Application is based on data from three Phase III studies of rivaroxaban involving nearly 10,000 patients in total, and an extensive phase I and phase II programme. One of the phase III studies was in patients undergoing total knee replacement surgery, the results of which were presented at the International Society on Thrombosis and Haemostasis (ISTH) in July 2007 (RECORD3). The results of the other two studies in patients undergoing hip replacement surgery (RECORD1 and RECORD2) will be presented at the upcoming 49th Annual Meeting of the American Society of Hematology (ASH) meeting, 8-11 December 2007.
The results of this study in 2,531 patients undergoing knee replacement surgery revealed that once-daily oral rivaroxaban 10 mg was superior in preventing VTE to once-daily subcutaneous enoxaparin 40 mg, the current standard of care therapy. Specifically, patients in this RECORD3 study (REgulation of Coagulation in major Orthopaedic surgery reducing the Risk of DVT and PE) who were treated with rivaroxaban demonstrated a 49 per cent relative risk reduction in the composite primary endpoint of deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and all-cause mortality compared to those treated with enoxaparin. Patients treated with rivaroxaban also had a 62 per cent reduced risk of developing major VTE (the composite of proximal DVT, non-fatal PE and VTE-related death), the main secondary endpoint of the trial. Importantly, there was a similar low rate of major bleeding for patients being treated with rivaroxaban and enoxaparin (0.6 per cent and 0.5 per cent, respectively).
To date, rivaroxaban is the most studied oral direct Factor Xa inhibitor in development. More than 20,000 patients have been evaluated in the completed Phase II programs and enrolled thus far in the Phase III programs. More than 40,000 patients are expected to be evaluated in total.
Upon regulatory approval, rivaroxaban will be commercialised in Europe by Bayer Schering Pharma. A filing for rivaroxaban for a similar indication in the United States is planned in 2008, where if approved, it will be will commercialised by Scios Inc. and Ortho-McNeil, Inc., both of which are Johnson & Johnson companies.