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collectBayerNews_20091206_0717_en.pdf BayerNews_20091206_0717_en.pdf
Treatment of Venous Thromboembolism (VTE):
Impressive 82% Relative Risk Reduction (RRR) in the Recurrence of Symptomatic VTE over Patients Treated with Placebo / Positive Benefit-Risk profile for Rivaroxaban Confirmed / First Phase III Data in the Chronic Setting to be Presented as a Late-Breaker at the Annual Meeting of the American Society of Hematology / Ongoing Discussions with FDA on Complete Response Letter for VTE Prevention After Total Knee and Hip Replacement Surgery
New Orleans, Louisiana (USA), December 6, 2009 - The novel oral anticoagulant
rivaroxaban 20 mg once-daily significantly reduced the risk of recurrent
symptomatic venous thromboembolism (VTE) compared to placebo in patients who
have been treated for a previous deep vein thrombosis (DVT) or pulmonary
embolism (PE). The rate of major bleeding was low. The results of the Phase III
EINSTEIN-Extension (EXT) clinical study were presented today in the official
press program of the 51st Annual Meeting of the American Society of Hematology
(ASH) in New Orleans, LA.
Rivaroxaban showed an 82% relative risk reduction (RRR) in the recurrence of
symptomatic VTE over patients treated with placebo [1.3% (n=8) vs. 7.1% (n=42),
respectively] - an outcome that was highly statistically significant
(p<0.0001).
"The results from EINSTEIN-EXT highlight the potential clinical benefit of
extending prophylaxis for an additional 6 or 12 months beyond the currently
recommended treatment duration," said Harry R. Büller, M.D., Academic Medical
Center in Amsterdam, Netherlands. "This study could help transform the way
physicians treat patients who have previously suffered a DVT or PE. Currently,
up to 10% of patients who are treated adequately, according to today's
recommended guidelines, still experience a recurrence within 12 months of the
initial event."
In the study, rivaroxaban was well tolerated and the rates of major bleeding,
the primary safety endpoint, were low and not statistically significantly
different (p=0.11) between the two groups [0.7% (n=4) vs. 0.0% (n=0), for the
rivaroxaban and placebo arms, respectively]. A secondary endpoint measuring the
composite of major and clinically relevant, but non-major bleeding, showed a
statistically significant difference (p<0.001) between="" the="" two="" groups="" 60="" n="7)" vs="" 12="" in="" rivaroxaban="" and="" placebo="" arms="" respectively="" liver="" safety="" results="" included:="" alt="">3x ULN: 1.9% in the rivaroxaban arm and 0.5% of
patients in the placebo arm; ALT >3x ULN + Total Bilirubin >2x ULN: n=0 in both
groups. No cases of serious liver injury were reported in either group. There
were no differences in the incidence of cardiovascular-related events between
the two treatment groups.
"We are delighted that rivaroxaban has now also shown benefit in a chronic
setting. Rivaroxaban has previously demonstrated superior efficacy to the
current standard treatment in the prevention of VTE after orthopedic surgery in
all four RECORD trials. Therefore, this is the fifth study in a row in a total
of more than 13,500 patients, in which rivaroxaban has shown consistent benefit
in reducing the risk of VTE in patients," said Kemal Malik, M.D., member of the
Board of Management of Bayer Schering Pharma AG, Germany, responsible for
Global Development.
To be eligible for enrollment in EINSTEIN-EXT, patients must have previously
completed 6 or 12 months of treatment with a vitamin K antagonist (VKA) for an
acute episode of VTE or had participated in the ongoing Phase III EINSTEIN-DVT
or EINSTEIN-PE trials, in which patients were treated with either rivaroxaban
or a VKA, for the same duration of time. Patients were then randomized to
receive either 20 mg of rivaroxaban dosed once-daily, or a placebo, and were
evaluated for an additional 6 or 12 months.
For further information, the abstract (lba-2) is available online at the ASH
website: http://ash.confex.com/ash/2009/webprogram/Paper25669.html
About the EINSTEIN Program
EINSTEIN is a global clinical development program composed of three clinical
studies in approximately 8,000 patients. Two of these studies enrolled patients
with acute, symptomatic deep vein thrombosis (EINSTEIN-DVT, enrollment
complete) 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 antagonist. The third study, EINSTEIN-EXT,
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 from 28
countries around the world with symptomatic DVT or PE. Approximately two
million cases of deep vein thrombosis and nearly 600,000 pulmonary embolism
cases are reported each year in the United States.
Update on FDA´s Complete Response Letter for VTE Prevention After Total Knee
and Hip Replacement Surgery
Rivaroxaban is currently under review by the U.S. Food and Drug Administration
(FDA) as one tablet, once-daily for the prophylaxis of deep vein thrombosis
(DVT) and pulmonary embolism (PE) in patients undergoing hip or knee
replacement surgery. The new drug application (NDA) for rivaroxaban was
submitted by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.,
on behalf of Ortho-McNeil Inc., on July 28, 2008. In March 2009, an FDA
Advisory Committee agreed by a vote of 15-2 that the available clinical data
for rivaroxaban demonstrated a favorable benefit-risk profile. In May 2009, the
FDA issued a Complete Response Letter for the NDA for rivaroxaban.
As previously announced, no new clinical or non-clinical studies to evaluate
the efficacy or safety of rivaroxaban were requested by the FDA as a
pre-requisite for approval. The Agency has asked the company to submit
additional data from completed and ongoing studies of rivaroxaban, and from
market surveillance from those countries outside the U.S. where the drug is
currently sold to further assess the benefit-risk profile of the drug. The FDA
also asked for additional information on RECORD study sites.
Following discussions with the FDA, Johnson & Johnson and Bayer are continuing
to provide additional information to address the questions raised in the
Complete Response Letter. Based on those discussions the companies have decided
not to submit its Complete Response to the FDA for approval of rivaroxaban for
the prevention of VTE after total knee and hip replacement surgery by the end
of 2009. Postponing the complete response until these requirements are fully
addressed provides the greatest opportunity for successfully bringing
rivaroxaban through the regulatory process.
Bayer will communicate an updated filing strategy in its Annual Press
Conference on February 26, 2010.
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.
About Rivaroxaban
Rivaroxaban is a novel oral anticoagulant that was invented in Bayer'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 shown a rapid onset of action with a
predicable dose response and high bioavailability, no requirement for
coagulation monitoring, and limited risk for food and drug interactions.
Rivaroxaban is marketed under the brand name Xarelto®. Approvals have been
granted for the prevention of VTE in adult patients undergoing elective hip or
knee replacement surgery in over 80 countries, including the EU, Australia,
Canada, China and Mexico. To date, Xarelto® has been launched in more than 50
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 expected to be enrolled into 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 VTE
treatment, stroke prevention in patients with atrial fibrillation, secondary
prevention of acute coronary syndrome, and VTE prevention in hospitalized,
medically ill patients.
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 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.
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