Biotech Values

[DewDiligence]

Daiichi Sankyo Enrolls 21,107(!) Patients in Edoxaban AF Trial

[Edoxaban (f/k/a DU-176b) is an oral FXa inhibitor similar to Xarelto and Apixaban, both of which have shown statsig phase-3 efficacy for stroke prevention in AF. Like Xarelto, Edoxaban has the advantage of qD dosing, but it has the drawback of requiring dose reduction in some patients with renal impairment, as is the case with Pradaxa (#msg-56742484).

The phase-3 trial that’s the subject of this PR started in Dec 2008 and is expected to finish in 1H12 (#msg-34100821); it was originally slated to have 16,500 patients, but the number somehow ballooned to 21,000+. Rather than following patients for a fixed time, this trial is event-driven, i.e. it proceeds until a prespecified number of stroke/embolism events have occurred in all arms combined. The trial is double-blinded and the comparator is warfarin, which means that clinicians perform faux warfarin monitoring for patients in the Edoxaban arms. This makes the trial more cumbersome to conduct, but it preempts the criticism of the pivotal trial for Pradaxa for being open-label.

Phase-2 data for Edoxaban in AF are in #msg-34100787.]

http://finance.yahoo.com/news/Daiichi-Sankyo-Completes-prnews-1332657057.html?x=0&.v=1

›Daiichi Sankyo Completes Enrollment of the Edoxaban Global Phase III ENGAGE AF-TIMI 48 Study in Patients With Atrial Fibrillation

More than 21,000 Patients Enrolled in the Largest Clinical Study with a Factor Xa Inhibitor

Wednesday December 1, 2010, 8:30 am EST

PARSIPPANY, N.J., Dec. 1, 2010 /PRNewswire-FirstCall/ -- Daiichi Sankyo Company, Limited (TSE:4568.to - News) announced today that it has successfully completed patient enrollment for 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 2.2 million Americans suffer from AF, and about 90,000 strokes in the U.S. each year are caused by 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 enrollment in November 2008. It is an event-driven, randomized, double-blind, double-dummy, parallel group, multi-center, multi-national 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 enrollment 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 (ENGAGE AF-TIMI 48), 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 [Systemic Embolic Events]. 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."‹