April 05, 2011
In the Prevention of VTE in Acutely ill Patients, Rivaroxaban Compares Favorably with Enoxaparin but Does Not Show a Consistent Net Clinical Benefit
MAGELLAN study meets primary efficacy endpoints of demonstrating non-inferiority in short-term use and superiority in long-term use / Primary analysis shows no consistent positive benefit-risk balance across heterogeneous patient population studiedBerlin, Germany, April 5, 2011 - Findings from the MAGELLAN Phase III clinical
study evaluating rivaroxaban for the prevention of venous thromboembolism (VTE)
in hospitalized patients with acute medical illness were presented today at the
60th American College of Cardiology (ACC) Annual Scientific Session.
In the study, rivaroxaban met its primary efficacy endpoints of demonstrating
non-inferiority to enoxaparin in short-term use (10 ± 4 days) and superiority
to enoxaparin (10 ± 4 days) followed by placebo in long-term use (35 ± 4 days)
in the prevention of VTE in hospitalized patients with acute medical illness.
The rates of major plus non-major clinically relevant bleeding, the study's
principal safety outcome, were low in both arms of the study, with unexpectedly
lower rates observed in the enoxaparin arm compared to patients receiving
"MAGELLAN investigated the largest and most diverse population of hospitalized,
acutely ill patients to date, and managing the risk of blood clots in these
patients is extremely complex due to their age, co-morbid conditions and
duration of immobilization. There is a continued risk of VTE beyond the initial
period of hospitalization or immobilization in
acutely ill patients," said Dr Alexander T. Cohen, MBBS MSc MD FRACP, King's
College Hospital, London, UK, and principal investigator. "As observed in a
previous study in this area, a consistently positive benefit-risk balance was
not seen across the heterogeneous, acutely ill patient population studied.
Further analysis is required to identify which groups of patients in MAGELLAN
may derive benefit from thromboprophylaxis with rivaroxaban."
In the MAGELLAN study, results for the primary efficacy endpoints (a composite
of asymptomatic proximal DVT detected by ultrasonography, symptomatic DVT,
non-fatal pulmonary embolism (PE), and VTE-related death) in the pre-specified
study durations were as follows:
In the short-term (10 ± 4 days) evaluation, rivaroxaban achieved
non-inferiority compared to enoxaparin [2.7% vs. 2.7%, p=0.0025] in the
Evaluated in the extended period (35 ± 4 days), rivaroxaban was superior to
short-term enoxaparin (10 ± 4 days) followed by placebo, in the modified
intent-to-treat (MITT) population [4.4% vs. 5.7%, respectively, RR 0.77,
The principal safety outcome was the incidence of treatment-emergent major
bleeding events and non-major, clinically relevant bleeding events observed no
later than two days after the last intake of the double-blind study drug. The
rates of primary safety events were low overall in both arms of the study, but
there was a statistically significant increase in patients randomized to
rivaroxaban compared with patients in the enoxaparin arm on Day 10 (2.8% vs.
1.2%, respectively; p<0.0001) and on Day 35 (4.1% vs. 1.7%, respectively;
p<0.0001). Rates of other adverse events, including liver and cardiovascular,
were similar across both study arms and rates for rivaroxaban were in line with
previous trial data.
About VTE in Medically ill Patients
Every year, venous blood clots kill more than 1 million people, including
approximately 300,000 in the US and more than 500,000 in Europe (1). VTE is
often associated with recent surgery or trauma, but 50-70% of symptomatic
thromboembolic events and 70-80% of fatal pulmonary embolism (PE) occur in
non-surgical patients(2). Hospitalization of acute medical illness is
independently associated with an approximated eightfold increase relative risk
for VTE (3), and accounts for almost one quarter of all VTE events in the
general population (2).
Patients hospitalized due to acute illnesses often have multiple risk factors
for VTE, which are generally cumulative (2). Complete immobility is a major
risk factor (2). Other conditions commonly associated with hospitalization can
increase the risk of VTE and include congestive heart failure, acute
respiratory disease, acute myocardial infarction, acute arthritis, acute
infection, cancer and inflammatory bowel disease (2,4,5).
About the MAGELLAN Study
MAGELLAN was a multi-national, randomized, double-blind, placebo-controlled
Phase III study investigating rivaroxaban for the prevention of VTE in patients
admitted to hospital with an acute medical illness (6). It evaluated 8,101
acutely ill medical patients from 52 countries, with a decreased level of
mobility including at least one day of complete immobilization during
hospitalization. MAGELLAN was designed to demonstrate the superior efficacy of
a 35 ± 4 day treatment period with oral rivaroxaban (10 mg once daily) for VTE
prophylaxis, compared to a 10 ± 4 day treatment period with subcutaneous
enoxaparin (40 mg once daily) followed by placebo in men and women >40 years of
age. Further, the study evaluated the non-inferiority of oral rivaroxaban for
VTE prophylaxis compared to standard of care enoxaparin in this patient
population at 10 ± 4 days.
The primary efficacy endpoints were a composite of asymptomatic proximal DVT
detected by ultrasonography, symptomatic DVT, non-fatal pulmonary embolism
(PE), and VTE-related death at Day 10 ± 4 and Day 35 ± 4, respectively. The
principal safety endpoint was a composite of major bleeding and clinically
relevant non-major bleeding6 at Day 10 and Day 35.
The demographics and baseline characteristics were balanced between treatment
groups. The groups were also equally balanced for acute medical conditions that
were the reason for hospital admission.
Rivaroxaban is an oral anticoagulant that was invented in Bayer HealthCare'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 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 80
countries by Bayer HealthCare.
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
evaluating the product in the prevention and treatment of a broad range of
venous and arterial thromboembolic diseases, including stroke prevention in
patients with atrial fibrillation, VTE treatment, and secondary prevention of
acute coronary syndrome (ACS).
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
health care, nutrition and high-tech materials. Bayer HealthCare, a subgroup of
Bayer AG with annual sales of EUR 16.913 billion (2010), 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, Consumer Care, Medical Care and Pharmaceuticals
divisions. Bayer HealthCare's aim is to discover and manufacture products that
will improve human and animal health worldwide. Bayer HealthCare has a global
workforce of 55,700 employees (Dec 31, 2010) and is represented in more than
100 countries. Find more information at www.bayerhealthcare.com.
Find more information at www.bayerpharma.com.