Daiichi Sankyo Company, Limited announced that it has successfully completed patient enrolment its phase III engage Af-timi 48 clinical study of edoxaban, a direct, specific, oral Factor Xa inhibitor that is being investigated in two different dosing regimens given once daily, to prevent the occurrence of strokes and Systemic Embolic Events (SEE) in patients with Atrial Fibrillation (AF).

An estimated 4.5 million people in Europe, 2.2 million Americans, and more than 800,000 people in Japan suffer from AF. Due to the aging population, the number of patients with AF worldwide is likely to increase 2.5 fold by the year 2050.

The Engage Af-timi 48 study began enrolment in November 2008. It is an event driven, randomized, double-blind, double-dummy, parallel group, multi-centre, multinational study designed to assess the efficacy and safety of edoxaban compared to the current standard of care, warfarin. Patients in the study are randomized to one of three treatment groups: 30 mg edoxaban once daily, 60 mg edoxaban once daily, or warfarin, a vitamin K antagonist. In addition, edoxaban doses are further adjusted to treat patients with renal impairment and/or low body weight, or those taking strong P-glycoprotein inhibitors. Those randomized to warfarin are dosed once daily to achieve an International Normalized Ratio (INR) between 2.0 and 3.0.

“The completion of enrolment for the largest AF outcomes study ever undertaken Engage Af-timi 48 -- marks a key milestone in the development of edoxaban and for Daiichi Sankyo,” said Glenn Gormley, MD, PhD, chief science officer & president, Daiichi Sankyo Pharma Development.

This phase III global AF study, Effective aNticoaGulation with factor xA next generation in Atrial Fibrillation, enrolled 21,107 subjects at nearly 1,400 clinical trial sites located throughout North America, South America, Africa, Asia, Europe and Australia/New Zealand. The primary endpoint of this study is to compare the efficacy of edoxaban to warfarin in the prevention of stroke and SEE. The primary safety assessment is the incidence of major bleeding events.

“As new options to prevent stroke in AF patients become available, it will be important that these treatments eliminate the need for extensive monitoring and dietary modifications,” said Elliott Antman, MD, Professor of Medicine, Harvard Medical School, Senior Investigator with the Brigham and Women's Hospital-based TIMI Study Group. “Based on phase II study results, edoxaban has shown promise of potentially addressing the needs of patients with AF and the physicians caring for them.”

Atrial fibrillation (AF) is an irregular heartbeat that is caused when the upper chambers of the heart (the atria) do not beat regularly and instead quiver erratically. When this happens, blood may stagnate in the atria leading to blood clots. These blood clots can break off and travel through the blood stream to the brain where they can plug the blood vessels, causing a stroke. AF is the most common type of clinically significant arrhythmia. Patients with AF have five times higher risk of having a stroke than individual without AF. These patients also tend to have more serious first strokes than patients without AF, resulting in higher mortality rates and longer hospital stays.

Edoxaban is a once-daily oral anticoagulant that directly inhibits Factor Xa, an important factor in the coagulation process. Edoxaban may offer physicians a wide therapeutic window to help address patients’ unique needs. Daiichi Sankyo is developing edoxaban 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 study these compounds in humans. Edoxaban is being developed solely by Daiichi Sankyo.

The Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address the diversified, unmet medical needs of patients in both mature and emerging markets.