New Phase II Data Show Safety of Once-Daily Oral Factor Xa Inhibitor, DU-176b, Comparable to Warfarin in Patients With Non-Valvular Atrial Fibrillation
atrial fibrillation receiving either 30 mg or 60 mg once-daily dose of
DU-176b, an investigational oral Factor Xa inhibitor, experienced comparable
safety and tolerability compared to those taking warfarin, according to new
Phase II data presented today at the 50th Annual Meeting of the American
Society of Hematology in
from a Phase II clinical study evaluating an oral Factor Xa inhibitor in
atrial fibrillation patients. DU-176b is being developed solely by Daiichi
Sankyo Company, Limited (TSE: 4568).
The objective of the multinational study was to assess the safety of four
dose regimens of DU-176b in patients with non-valvular atrial fibrillation
(AF), as compared to warfarin. While the incidence of major and clinically
relevant non-major bleeding events was significantly higher in the twice-daily
DU-176b treatment groups (30 mg or 60 mg twice per day), compared with
warfarin, the incidence reported in the once-daily DU-176b treatment groups
(30 mg or 60 mg once per day) was similar to that in the warfarin-treated
patient group. Bleeding events were evaluated using guidelines established by
the International Society on Thrombosis and Haemostasis(1), the most sensitive
scale of those currently used in clinical studies in cardiovascular disease.
“These results are noteworthy and encouraging because we observed
significantly fewer adverse bleeding events in patients receiving one dose of
DU-176b per day, versus two doses per day, suggesting with this compound, the
most convenient dosing regimens also appear to be safer,” said
Weitz
University
data provide insight into the optimal dosing regimens for Phase III studies of
DU-176b.”
“Having clear results from a robust Phase II study among atrial
fibrillation patients gives us confidence in evaluating the doses selected for
our Phase III clinical trial,” said Francis Plat, M.D., vice president,
clinical development at Daiichi Sankyo Pharma Development. “We are hopeful
that DU-176b may one day provide the community with a safe and convenient
treatment for the prevention of stroke in patients with non-valvular atrial
fibrillation.”
About the DU-176b Phase II Safety Study
A total of 1,146 patients with atrial fibrillation with a CHADS2 index >/=
2 were enrolled in the study. Patients were randomly assigned to receive
either one of the four fixed dose regimens of DU-176b (30mg/N=235 or
60mg/N=234 administered once daily; 30mg/N=244 or 60mg/N=180 administered
twice daily), or warfarin (N=250) dose-adjusted locally to a target
International Normalized Ratio (INR) of 2.0-3.0 for 12 weeks. The INR was
determined weekly for four weeks and every two weeks thereafter.
Investigators, sponsors and study subjects were blinded to the DU-176b dose;
however, those taking warfarin were aware they were randomized to the warfarin
arm.
The primary endpoints of the study were the incidence of bleeding events
(major and clinically relevant non-major) and elevated liver enzymes and/or
bilirubin. Secondary endpoints included major adverse cardiovascular events,
stroke, systemic embolism, acute myocardial infarction, hospitalizations due
to cardiovascular conditions or cardiovascular death.
The incidence of major and clinically relevant non-major bleeding events
was significantly higher with the 30 mg and 60 mg twice-daily DU-176b regimens
(7.8 percent, p = 0.029 and 10.6 percent, p = 0.002 respectively) than it was
in patients given warfarin (3.2 percent). In contrast, the incidence of major
and clinically relevant non-major bleeding events with the 30 mg and 60 mg
once-daily DU-176b regimens was comparable to that with warfarin (3.0 percent,
3.8 percent and 3.2 percent, respectively). There were no significant
differences in the numbers of patients with elevated liver enzymes or
bilirubin across all treatment groups. Although the study was not powered to
detect efficacy, there were no significant differences in the rates of
secondary efficacy endpoints across treatment groups.
About Atrial Fibrillation
Atrial fibrillation is an irregular heartbeat caused when the upper
chambers of the heart (the atria) beat inconsistently and rapidly. When this
happens, blood can become stagnant near the walls of the atria and form blood
clots. These blood clots can break off and travel through the blood stream to
the brain where they can plug blood vessels possibly causing a stroke. These
clots can also cause damage to other organs in the body by blocking peripheral
arteries.
Approximately 90,000 strokes in the U.S. result from atrial
fibrillation.(2) Patients with atrial fibrillation have five times higher
risk of having a stroke.(3) These patients also tend to have more serious
first strokes than those without atrial fibrillation, resulting in higher
mortality rates and longer hospital stays.(1)
About DU-176b
DU-176b is an oral anticoagulant that directly inhibits Factor Xa, a
clotting factor in the blood. Daiichi Sankyo is developing DU-176b as a
potential new treatment for the prevention of both arterial and venous
thromboembolism. Notably, Daiichi Sankyo has more than 25 years experience
conducting research in the area of Factor Xa inhibition and was the first
company to test these compounds in humans.
About Daiichi Sankyo
A global pharma innovator, Daiichi Sankyo Co., Ltd., was established in
2005 through the merger of two leading Japanese pharmaceutical companies. This
integration created a more robust organization that allows for continuous
development of novel drugs that enrich the quality of life for patients around
the world. A central focus of Daiichi Sankyo’s research and development are
thrombotic disorders, malignant neoplasm, diabetes mellitus, and autoimmune
disorders. Equally important to the company are hypertension, hyperlipidemia
or atherosclerosis and bacterial infections. For more information, visit
www.daiichisankyo.com.
Daiichi Sankyo, Inc., headquartered in
subsidiary of Daiichi Sankyo Co., Ltd. For more information on Daiichi Sankyo,
Inc., please visit www.dsus.com.
Forward-Looking Statements This news release may contain forward-looking
statements based on current assumptions and forecasts made by Daiichi Sankyo
group. Various known and unknown risks, uncertainties and other factors could
lead to material differences between the actual future results, financial
situation, development or performance of the company and the estimates given
here. These factors include those discussed in our public reports, which are
available on the website at www.daiichisankyo-us.com. The company assumes no
liability whatsoever to update these forward-looking statements or to conform
them to future events or developments.
1. Schulman S., et al. Definition of major bleeding in clinical
investigations of antihemostatic medicinal products in non-surgical patients.
Journal of Thrombosis and Haemostasis 2005;3: 692-694.
2. Jorgensen, H.S., Nakayama, H, Reith, J. et. al. Acute stroke with
atrial fibrillation. Stroke 1996;27: 1765-1769.
3. Hylek AM, et al. N Engl J Med. 2003; 349:1019-1026.
For more information, please contact:
Toshiaki Sai
Daiichi Sankyo Company, Limited (Tokyo)
Phone: +81-3-6225-1126
Dr. Felix Munzel
Daiichi Sankyo Europe GmbH
Phone: + 49-(0)-89-7808-471
Kimberly Wix
Daiichi Sankyo, Inc. (United States)
Phone: +1 (973) 695-8338
Mobile : +1 (908) 656-5447
Dr. Thomas Portz
Daiichi Sankyo Europe GmbH
Phone: + 49 (0)89-78 08 468
Mobile: + 49 (0)172-841 5904
Abstract Number: 33
SOURCE Daiichi Sankyo Company, Limited