Daiichi Sankyo's edoxaban non-inferior to warfarin in late-stage study

Study data published in the NEJM revealed that Daiichi Sankyo's experimental direct factor Xa-inhibitor edoxaban was non-inferior to warfarin in preventing strokes and embolisms in certain patients with atrial fibrillation (AF) in a Phase III trial. Findings of the study were also presented at the American Heart Association annual meeting.

The ENGAGE AF-TIMI 48 trial involved 21 105 patients with non-valvular AF at moderate-to-high risk of thromboembolic events who were randomised to receive one of two doses of edoxaban given once-daily or placebo. The treatment arms were compared for a median of 2.8 years. The main efficacy goal was the time to first stroke or systemic embolic event (SEE), while the principal safety outcome was major bleeding.

Results demonstrated that the annual incidence of stroke or SEE was 1.2 percent in the high-dose edoxaban arm, versus 1.5 percent for warfarin. The higher dose also significantly reduced major bleeding by 20 percent, with an annual rate of 2.8 percent, versus 3.4 percent for the warfarin group. The company noted that the low-dose edoxaban arm significantly lowered major bleeding by 53 percent, with an annual rate of 1.6 percent, compared to warfarin. Further, the annual incidence of intracranial haemorrhage was 0.39 percent and 0.26 percent for the high- and low-dose edoxaban arms, respectively, versus 0.85 percent in the warfarin group. Daiichi Sankyo's drug was also associated with annual rates of cardiovascular death of about 2.7 percent in both edoxaban groups, compared with 3.2 percent for warfarin.

Sanford C. Bernstein & Co. analyst Timothy Anderson described the data as "fairly lackluster," adding that he nonetheless expects edoxaban to garner regulatory approval and for Daiichi Sankyo to potentially gain a partner, such as Merck & Co. or AstraZeneca, for sale in the US and Europe. Anderson noted that Merck and AstraZeneca "have a cardiovascular presence and need new products."

Still, Glenn Gormley, Daiichi Sankyo's global head of R&D and its executive chairman in the US, said "the edoxaban clinical trial programme...has now yielded positive data for edoxaban in two major diseases, stroke prevention in AF and treatment of acute venous thromboembolism (VTE)." He stated that based on the data from ENGAGE AF-TIMI 48, as well as from the Phase III Hokusai-VTE trial, the company plans to file new drug applications for edoxaban in both indications by the first quarter of 2014 in the US, Japan and Europe. Edoxaban was approved in Japan in 2011 for the prevention of VTE after major orthopaedic surgery.

For analysis on expectations for other next-generation anticoagulants, see Spotlight On: Expectations wilting for Bristol-Myers Squibb, Pfizer's Eliquis as Bayer's Xarelto goes from strength to strength.

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