Prevention of Venous Thromboembolism after Major Orthopedic Surgery:
Bayer HealthCare Submits Rivaroxaban for European Approval
- Data Package for Rivaroxaban Involves Nearly 10,000 Patients in Three Phase III Trials
Oct 31st, 2007 - Bayer HealthCare AG announced today 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 orthopedic 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,” said Dr. Kemal Malik, Head of Global evelopment and member of the Bayer HealthCare Executive Committee. “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 orthopedic surgery.”
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 Prevention of Venous Thromboembolism after Major Orthopedic Surgery:
Bayer HealthCare Submits Rivaroxaban for European Approval Data Package for Rivaroxaban Involves Nearly 10,000 Patients in Three Phase III Trials that up to 50% 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 program. 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 Hemostasis (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 Orthopedic surgery reducing the Risk of DVT and PE) who were treated with rivaroxaban demonstrated a 49% relative risk reduction (p<0.001) 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%
reduced risk (p=0.01) 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% and 0.5%, respectively).
About Rivaroxaban (Xarelto)
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 commercialized 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 commercialized by Scios Inc. and Ortho-McNeil, Inc., both of which are Johnson & Johnson companies.
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our annual and interim reports to the Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
- Factor Xa
- Pivotal component of blood clotting cascade. Stimulates the production of thrombin, the enzyme in the coagulation cascade that promotes the formation of blood clots.
- Venous thromboembolism
- A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
- Formation of a clot inside a blood vessel.
- Relative Risk Reduction
- Proportion of the control group experiencing a given outcome minus the proportion of the treatment group experiencing the outcome, divided by the proportion of the control group experiencing the outcome.
- Introduced beneath the skin.
- Deep vein thrombosis
- A blood clot in a deep vein, usually resulting from damage to the vein or blood flow slowing down or stopping. Usually DVTs are found in the leg, but can also be in the arm. Distal DVTs are found in deep veins of the calf, and are the most common type of DVT. Proximal DVTs are found in the legs above the calf muscle up to the waist.
- Pulmonary embolism
- A potentially fatal condition caused by a blood clot blocking a vessel in the lung: usually the clot originates from a DVT in the legs. PE can result in permanent lung damage.