Enthusiasm for Emerging Anticoagulants Now Tempered

D'oh. Color me prematurely giddy for an emerging anticoagulant market that might unseat warfarin from its dusty throne. Don't get me wrong: I'm still praising Jebus for the FDA approval of BI's Pradaxa (dabigatran)—pending some horrific and unexpected side effect that turns up in the vast postmarketing experience. And the prospects for Bayer Healthcare's Xarelto (rivaroxaban) remain excellent.

But another contender, BMS/Pfizer's apixaban just hit a big development brick wall. Excess bleeding in the APPRAISE-2 trial, a large phase 3 study of the factor Xa inhibitor (like Xarelto) in patients with acute coronary syndrome (ACS), has led to a halt of the trial, says a joint company press release. "There was clear evidence of a clinically important increase in bleeding among patients randomized to apixaban. This increase in bleeding was not offset by clinically meaningful reductions in ischemic events," wrote BMS and Pfizer.

The APPRAISE-2 trial was just 1 of 9 trials assessing the potential benefits of apixaban in patients at risk of ischemic events. Other populations in which apixaban is being investigated by the companies are a-fib patients (two phase 3 studies according to clinicaltrials.gov) and patients with venous thromboembolism (one phase 3 study per clinicaltrials.gov).

One of the phase 3 a-fib trials of apixaban (AVERROES) is in "patients who have failed or are unsuitable for vitamin K antagonist treatment" (eg, warfarin) and contains an aspirin comparator arm. The study completion date is September 2012. The other a-fib study of apixaban (ARISTOTLE), with a warfarin comparator arm, is expected to be completed in April of next year.

APPRAISE-2 = Apixaban for Prevention of Acute Ischemic Events-2.