August 31, 2010
Bayer's Rivaroxaban Successfully Meets Primary Efficacy Outcome and Demonstrates Similar Safety to Standard Therapy in Phase III EINSTEIN-DVT Non-Inferiority Study
Results from EINSTEIN-DVT Study Presented at European Society of Cardiology Congress 2010Berlin, Germany, August 31, 2010 - The Phase III EINSTEIN-DVT clinical trial of
the oral anticoagulant rivaroxaban demonstrated non-inferiority compared to the
standard of care for the prevention of recurrent venous thromboembolism (VTE)
in patients with acute symptomatic deep vein thrombosis (DVT), with a
comparable safety profile. The data were presented today during a Hot Line
session at the European Society of Cardiology (ESC) Congress.
"Results from EINSTEIN-DVT could transform the way physicians treat deep vein
thrombosis," said lead investigator Harry R. Büller, M.D., Academic Medical
Center in Amsterdam, Netherlands, who presented the results. "While the current
standard of care is effective when well-controlled, it is often associated with
significant drawbacks for patients and physicians. A novel single-drug approach
such as oral rivaroxaban could potentially provide an effective and
well-tolerated, simple, fixed-dose regimen for the treatment of deep vein
thrombosis as a replacement for current standard therapy."
In the study, oral rivaroxaban demonstrated non-inferiority for the primary
efficacy outcome, defined as the cumulative incidence of symptomatic recurrent
DVT and non-fatal or fatal PE, in patients with acute symptomatic DVT compared
with the current standard of care of enoxaparin followed by a vitamin K
antagonist (VKA) [2.1% vs. 3.0%, respectively (p <0.0001 for non-inferiority)].
Rivaroxaban also demonstrated similar results compared to the standard of care
for the principal safety outcome measuring a composite of major and non-major
clinically relevant bleeding events [8.1% in both treatment groups, (p=0.77)].
Monthly liver function tests did not reveal a signal for impaired liver safety.
Rivaroxaban was well tolerated in the study, and discontinuation rates related
to adverse events were low and similar in both treatment groups.
Net clinical benefit, a pre-specified secondary outcome defined as the
composite of the primary efficacy outcome plus major bleeding, demonstrated an
improvement for rivaroxaban compared to standard therapy (2.9% vs. 4.2%,
respectively; HR of 0.67, CI: 0.47 - 0.95). Other presented secondary outcomes,
including all-cause mortality (2.2% vs. 2.9%, respectively; HR of 0.67, CI:
0.44 - 1.02) and cardiovascular events (0.7% vs. 0.8%, respectively; HR of
0.79, CI: 0.36 - 1.71) were not statistically significantly different.
EINSTEIN-DVT is the sixth Phase III trial in the ongoing rivaroxaban global
development program that demonstrated either non-inferiority (EINSTEIN-DVT) or
superiority (RECORD1-4 and EINSTEIN-EXTENSION).
Bayer's first regulatory filings in the VTE treatment setting are planned for
the second half of 2010.
About the EINSTEIN Clinical Trial Program
EINSTEIN is a global clinical development program composed of three clinical
studies in nearly 9,000 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 non-inferiority study involving more than 3,400 patients with acute
symptomatic DVT, but without any symptoms of PE. Standard therapy for 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), to optimize efficacy and 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 DVT and non-fatal or fatal PE. The principal safety
outcome is the composite of major and clinically relevant non-major bleeding.
The third study, EINSTEIN-Extension, evaluated the efficacy and safety of
rivaroxaban compared 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 in patients who had been treated for
a previous acute deep vein thrombosis (DVT) or pulmonary embolism (PE), oral
rivaroxaban 20 mg once-daily significantly reduced the risk of recurrent
symptomatic venous thromboembolism (VTE) by 82 % compared to placebo. The rate
of major bleeding was low.
About Deep Vein Thrombosis (DVT)
DVT is the formation of a blood clot in a deep vein that partially or totally
blocks the flow of blood. It is estimated that more than 680,000 DVT events
occur in the EU each year. The majority of patients suffering from a venous
blood clot will experience a DVT alone. However, DVT can progress to become a
potentially fatal PE if the blood clot breaks apart and travels to the lungs,
ultimately blocking a blood vessel there. Even in the absence of a PE, DVT
alone can have burdensome and costly consequences such as post-thrombotic
syndrome and an increased risk of recurring blood clots, therefore achieving
treatment goals is essential.
Standard therapy for DVT currently includes two compounds: low molecular weight
heparin administered by subcutaneous injection, followed by a vitamin K
antagonist. The multinational EINSTEIN-DVT study compared the efficacy and
safety of a novel single-drug approach with rivaroxaban to current dual
standard therapy in a study involving more than 3,400 patients with acute
symptomatic DVT in the deep veins of the knee or thigh, but without any
symptoms of PE.
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. 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.