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
The objective of the multinational study was to assess the safety of fourdose regimens of DU-176b in patients with non-valvular atrial fibrillation(AF), as compared to warfarin. While the incidence of major and clinicallyrelevant non-major bleeding events was significantly higher in the twice-dailyDU-176b treatment groups (30 mg or 60 mg twice per day), compared withwarfarin, 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-treatedpatient group. Bleeding events were evaluated using guidelines established bythe International Society on Thrombosis and Haemostasis(1), the most sensitivescale of those currently used in clinical studies in cardiovascular disease.
"These results are noteworthy and encouraging because we observedsignificantly fewer adverse bleeding events in patients receiving one dose ofDU-176b per day, versus two doses per day, suggesting with this compound, themost convenient dosing regimens also appear to be safer," said Jeffrey I.Weitz, MD, FACP, FRCP, professor of medicine and biochemistry, McMasterUniversity and director, Henderson Research Centre, Hamilton, Ontario. "Thesedata provide insight into the optimal dosing regimens for Phase III studies ofDU-176b."
"Having clear results from a robust Phase II study among atrialfibrillation patients gives us confidence in evaluating the doses selected forour Phase III clinical trial," said Francis Plat, M.D., vice president,clinical development at Daiichi Sankyo Pharma Development. "We are hopefulthat DU-176b may one day provide the community with a safe and convenienttreatment for the prevention of stroke in patients with non-valvular atrialfibrillation."
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 receiveeither one of the four fixed dose regimens of DU-176b (30mg/N=235 or60mg/N=234 administered once daily; 30mg/N=244 or 60mg/N=180 administeredtwice daily), or warfarin (N=250) dose-adjusted locally to a targetInternational Normalized Ratio (INR) of 2.0-3.0 for 12 weeks. The INR wasdetermined 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 warfarinarm.
The primary endpoints of the study were the incidence of bleeding events(major and clinically relevant non-major) and elevated liver enzymes and/orbilirubin. Secondary endpoints included major adverse cardiovascular events,stroke, systemic embolism, acute myocardial infarction, hospitalizations dueto cardiovascular conditions or cardiovascular death.
The incidence of major and clinically relevant non-major bleeding eventswas 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 wasin patients given warfarin (3.2 percent). In contrast, the incidence of majorand clinically relevant non-major bleeding events with the 30 mg and 60 mgonce-daily DU-176b regimens was comparable to that with warfarin (3.0 percent,3.8 percent and 3.2 percent, respectively). There were no significantdifferences in the numbers of patients with elevated liver enzymes orbilirubin across all treatment groups. Although the study was not powered todetect efficacy, there were no significant differences in the rates ofsecondary efficacy endpoints across treatment groups.
About Atrial Fibrillation
Atrial fibrillation is an irregular heartbeat caused when the upperchambers of the heart (the atria) beat inconsistently and rapidly. When thishappens, blood can become stagnant near the walls of the atria and form bloodclots. These blood clots can break off and travel through the blood stream tothe brain where they can plug blood vessels possibly causing a stroke. Theseclots can also cause damage to other organs in the body by blocking peripheralarteries.
Approximately 90,000 strokes in the U.S. result from atrialfibrillation.(2) Patients with atrial fibrillation have five times higherrisk of having a stroke.(3) These patients also tend to have more seriousfirst strokes than those without atrial fibrillation, resulting in highermortality rates and longer hospital stays.(1)
DU-176b is an oral anticoagulant that directly inhibits Factor Xa, aclotting factor in the blood. Daiichi Sankyo is developing DU-176b as apotential new treatment for the prevention of both arterial and venousthromboembolism. Notably, Daiichi Sankyo has more than 25 years experienceconducting research in the area of Factor Xa inhibition and was the firstcompany to test these compounds in humans.
About Daiichi Sankyo
A global pharma innovator, Daiichi Sankyo Co., Ltd., was established in2005 through the merger of two leading Japanese pharmaceutical companies. Thisintegration created a more robust organization that allows for continuousdevelopment of novel drugs that enrich the quality of life for patients aroundthe world. A central focus of Daiichi Sankyo's research and development arethrombotic disorders, malignant neoplasm, diabetes mellitus, and autoimmunedisorders. Equally important to the company are hypertension, hyperlipidemiaor atherosclerosis and bacterial infections. For more information, visitwww.daiichisankyo.com.
Daiichi Sankyo, Inc., headquartered in Parsippany, New Jersey, is the U.S.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-lookingstatements based on current assumptions and forecasts made by Daiichi Sankyogroup. Various known and unknown risks, uncertainties and other factors couldlead to material differences between the actual future results, financialsituation, development or performance of the company and the estimates givenhere. These factors include those discussed in our public reports, which areavailable on the website at www.daiichisankyo-us.com. The company assumes noliability whatsoever to update these forward-looking statements or to conformthem to future events or developments.
1. Schulman S., et al. Definition of major bleeding in clinicalinvestigations 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 withatrial 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
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