August 04, 2010
Bayer's Rivaroxaban Meets Primary Endpoint in Long-Term Phase III EINSTEIN-DVT Study
Rivaroxaban shows superiority to standard therapy in net clinical benefit, a secondary endpoint of the study / Rivaroxaban well tolerated in this long-term trial / Full data set to be presented at Hot Line Session at ESC 2010Berlin, Germany, August 4, 2010 - Bayer today announced that a novel,
convenient single-drug treatment approach with oral rivaroxaban met the primary
efficacy endpoint of non-inferiority in the EINSTEIN-DVT Phase III clinical
trial and showed an overall relative risk reduction compared to the current
standard therapy in the treatment of deep vein thrombosis (DVT) - initial
enoxaparin treatment, followed by a vitamin K antagonist. The primary efficacy
outcome in this non-inferiority trial involving more than 3,400 patients was
the cumulative incidence of symptomatic recurrent venous thromboembolism
(non-fatal or fatal).
Compared to standard therapy rivaroxaban conveyed a significantly improved net
clinical benefit, a pre-specified secondary outcome defined as the composite of
the primary efficacy endpoint plus major bleeding.
"The results of this study confirm that the novel, convenient single drug
treatment approach with rivaroxaban could replace the current standard therapy
in the treatment of patients suffering from deep vein thrombosis," said Kemal
Malik, M.D., member of the Executive Committee of Bayer HealthCare and Chief
Rivaroxaban was well tolerated and the rate for the composite of major and
clinically relevant non-major bleeding, the primary safety outcome of the
study, was similar to current standard therapy. Overall safety findings in this
long-term trial are in line with existing clinical data and once again confirm
the good benefit/risk profile for rivaroxaban.
The full data set from the Phase III EINSTEIN-DVT study will be presented at
the Hot Line Session on August 31, 2010, 11:00-12:30 CET, at the Annual Meeting
of the European Society of Cardiology (ESC) in Stockholm, Sweden, by lead
investigator Harry R. Buller, MD, Academic Medical Center, Amsterdam, the
About the EINSTEIN Clinical Trial Program
EINSTEIN is a global clinical development program composed of three clinical
studies in more than 8,000 patients: EINSTEIN-DVT, EINSTEIN-PE and
EINSTEIN-Extension. Two of these studies enrolled patients with acute,
symptomatic deep vein thrombosis (EINSTEIN-DVT) or pulmonary embolism
(EINSTEIN-PE). In these two trials, patients received oral rivaroxaban 15 mg
twice-daily for the first three weeks, followed by oral rivaroxaban 20 mg
once-daily, compared with initial enoxaparin treatment followed by a vitamin K
The multinational Phase III EINSTEIN-DVT study investigated a new single-drug
approach with rivaroxaban compared with standard therapy in a randomized,
open-label, assessor-blind, non-inferiority study involving more than 3,400
patients with acute symptomatic deep vein thrombosis (DVT), but without any
symptoms of pulmonary embolism (PE). Standard therapy for venous
thromboembolism, including DVT, currently includes two compounds: low molecular
weight heparin administered by subcutaneous injection, followed by a vitamin K
antagonist, which requires regular monitoring of the prothrombin time, reported
as the International Normalized Ratio (INR), for safety.
Patients received either oral rivaroxaban or body weight-adjusted enoxaparin
followed by warfarin or acenocoumarol, dose adjusted to maintain a therapeutic
INR (target 2.5, range 2.0-3.0), for 3, 6 or 12 months, based on the
physician's assessment at baseline. The primary efficacy outcome of
EINSTEIN-DVT is the cumulative incidence of symptomatic recurrent venous
thromboembolism (VTE), non-fatal or fatal pulmonary embolism (PE). The
principal safety outcome is the composite of major and clinically relevant
The third study, EINSTEIN-Extension, compared the efficacy and safety of
rivaroxaban to placebo in the secondary prevention of recurrent symptomatic
venous blood clots by extending preventative treatment by 6 or 12 months beyond
a previously completed regimen of 6 or 12 months of therapy, and enrolled
approximately 1,200 patients with symptomatic DVT or PE. The results of the
Phase III EINSTEIN-Extension study were presented in December 2009 at the 51st
Annual Meeting of the American Society of Hematology (ASH) in New Orleans
(USA). The data demonstrated that oral rivaroxaban 20 mg once-daily
significantly reduced the risk of recurrent symptomatic venous thromboembolism
(VTE) by 82 % compared to placebo in patients who had been treated for a
previous deep vein thrombosis (DVT) or pulmonary embolism (PE). The rate of
major bleeding was low.
Rivaroxaban is a novel oral anticoagulant that was invented in Bayer Schering
Pharma's Wuppertal laboratories in Germany, and is being jointly developed by
Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development,
L.L.C. In clinical studies, rivaroxaban has been shown to be effective in
preventing VTE in adult patients following elective hip or knee replacement
surgery. It has a rapid onset of action with a predictable dose response and
high bioavailability, no requirement for coagulation monitoring, as well as a
limited potential for food and drug interactions. Rivaroxaban is marketed under
the brand name Xarelto® for VTE prevention in adult patients following elective
hip or knee replacement surgery, and it is the only new oral anticoagulant that
has consistently demonstrated superior efficacy over enoxaparin for this
indication. Xarelto® is approved in more than 100 countries worldwide and has
been successfully launched in more than 75 countries by Bayer Schering Pharma
achieving the market leader position among the new oral anticoagulants.
The extensive clinical trial program supporting rivaroxaban makes it the most
studied oral, direct Factor Xa inhibitor in the world today. More than 65,000
patients are participating in the rivaroxaban clinical development program,
which will evaluate the product in the prevention and treatment of a broad
range of acute and chronic blood-clotting disorders, including stroke
prevention in patients with atrial fibrillation, secondary prevention of acute
coronary syndrome, and VTE prevention in hospitalized, medically ill patients.
If approved by the FDA, Ortho-McNeil, a division of Ortho-McNeil-Janssen
Pharmaceuticals, Inc. (a Johnson & Johnson Company), will commercialize
rivaroxaban in the U.S. The U.S. Bayer HealthCare sales force will support the
Ortho-McNeil sales force by detailing rivaroxaban in designated hospital
accounts. Bayer HealthCare is exclusively responsible for the marketing of
rivaroxaban in countries outside the U.S.
To learn more about thrombosis, please visit www.thrombosisadviser.com.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of
healthcare, nutrition and high-tech materials. Bayer HealthCare, a subsidiary
of Bayer AG, is one of the world's leading, innovative companies in the
healthcare and medical products industry and is based in Leverkusen, Germany.
The company combines the global activities of the Animal Health, Bayer Schering
Pharma, Consumer Care and Medical Care divisions. Bayer HealthCare's aim is to
discover, manufacture and market products that will improve human and animal
health worldwide. Find more information at www.bayerhealthcare.com.
About Bayer Schering Pharma
Bayer Schering Pharma is a worldwide leading specialty pharmaceutical company.
Its research and business activities are focused on the following areas:
Diagnostic Imaging, General Medicine, Specialty Medicine and Women's
Healthcare. With innovative products, Bayer Schering Pharma aims for leading
positions in specialized markets worldwide. Using new ideas, Bayer Schering
Pharma aims to make a contribution to medical progress and strives to improve
the quality of life. Find more information at www.bayerscheringpharma.de.