Edoxaban - Factor Xa Inhibitor Enters Phase III With Optimal Dose

MUNICH - Edoxaban (DU-176b) is a direct Factor Xa inhibitor and is developed to
prevent thromboembolic events such as stroke and pulmonary embolism. The
Phase II Edoxaban programme has been successfully completed for orthopaedic
and cardiological indications.

For the time being it is evident that Edoxaban is currently the only
Factor Xa inhibitor with a dose-ranging study conducted with patients with
atrial fibrillation and is, thus, starting with optimal dosing in clinical
Phase III.

Edoxaban’s Phase II results for patients with atrial fibrillation were
presented at the American Society of Hematology’s 50th annual conference
last December in San Francisco. For patients who received 60 mg or 30 mg
of Edoxaban once per day, safety and tolerability were shown to be comparable
to the vitamin K antagonist Warfarin.

These are the first results worldwide from a clinical study of
anticoagulation using an oral Factor Xa inhibitor in patients
with atrial fibrillation. The primary goal of this international study
was to test the safety of four Edoxaban dosing regimens in comparison to
Warfarin. Whilst the frequency of severe and clinically significant
non-severe bleedings in the treatment group in which Edoxaban
was administered twice a day (60 mg or 30 mg twice daily) was
significantly higher in comparison to Warfarin, the frequency in the
treatment group receiving one dose a day (Edoxaban 60 mg or 30
mg once daily) was comparable with the incidence in the Warfarin treated
patients.

“These results are noteworthy and encouraging, since we observed
significantly fewer undesired bleeding events in patients who received
Edoxaban once a day in comparison to those with a twice daily dose. This
indicates that, for this drug, the most convenient dosing schema also seems
to be the safer one,” said the presenter of the study, Jeffrey I. Weitz, MD,
FACP, FRCP, Professor of Medicine and Biochemistry, McMaster University and
Director of the Henderson Research Centre, Hamilton (Ontario, Canada).

This dose-ranging study - currently the only one conducted so far using a
Factor Xa inhibitor in patients with atrial fibrillation - provided crucial
insights with regard to the optimal dosage of Edoxaban for the Phase III
study ENGAGE-AF TIMI 48 (Effective Anticoagulation with Factor Xa Next
Generation in Atrial Fibrillation), which has already begun.

In this multi-centre, double-blind and randomised study, approx. 16,500
patients will be assigned to one of three treatment groups: 30 mg Edoxaban
once daily, 60 mg Edoxaban once daily and Warfarin. Patients in the Warfarin
group will receive Warfarin once a day, with the dosage adjusted so that the
coagulation parameters lie within a certain target range (INR values between
2.0 and 3.0). Edoxaban will be compared to Warfarin with regard to the
prevention of strokes and systemic embolic events in patients with atrial
fibrillation. The frequency of occurrence of severe and clinically
significant non-severe bleedings will be used as the primary safety end
point.

Approx. 4.5 million people suffer from atrial fibrillation in Europe.

Irregular and rapid beating of the heart’s atria can lead to pooling of
the blood in places and thus to the formation of blood clots (thromboses).
These thromboses can become detached and be carried in the circulation to the
brain where they cause strokes by blocking blood vessels. Without
anticoagulation treatment, patients with atrial fibrillation have a five
times higher risk of having a stroke. The ENGAGE-AF TIMI 48 study is
therefore intended to show that these patients can be treated simply,
effectively and safely with the Factor Xa inhibitor Edoxaban. The expected
median treatment duration in the study is 24 months; the sponsor DAIICHI
SANKYO expects the study to conclude in the first half of 2012.

Press contact:
Dr. Felix Munzel,
Medical/Scientific Affairs CV Europe,
felix.muenzel@daiichi-sankyo.eu

Dr. Roland Derwand,
New Product Planning CV Europe
DAIICHI SANKYO EUROPE GmbH,
Telephone +49(0)89-7808-0

www.daiichi-sankyo.eu

Source: DAIICHI SANKYO EUROPE GmbH

Press contact: Dr. Felix Munzel, Medical/Scientific Affairs CV Europe, felix.muenzel at daiichi-sankyo.eu; Dr. Roland Derwand, New Product Planning CV Europe; DAIICHI SANKYO EUROPE GmbH, Telephone +49(0)89-7808-0