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Data from a mid-stage study presented at the European Society of Cardiology meeting suggest Astellas' experimental oral anticoagulant darexaban increased bleeding two- to four-fold in patients with acute coronary syndrome (ACS). While the Factor Xa inhibitor also failed to produce a decrease in rates of death, strokes or heart attack, compared with placebo, researchers said the trial was too small to assess efficacy with any certainty.

Multiple doses of darexaban were tested in combination with dual antiplatelet therapy in the 1279-patient RUBY-1 study, and results showed that bleeding increased with higher dosages. Commenting on the results, lead researcher Gabriel Steg remarked that "I think we have a series of mixed signals. It is probably a little too soon to forgo the idea of adding anticoagulants to anti-platelet therapy." Steg added that "establishing the role of low-dose darexaban in preventing major cardiac events after ACS now requires a large Phase III trial." Meanwhile, David Holmes, president of the American College of Cardiology, indicated that use of anticoagulants in ACS should continue to be investigated, but said a low dose of darexaban would be needed in future trials.

Earlier this week at the conference, Pfizer and Bristol-Myers Squibb presented positive late-stage results for the Factor Xa inhibitor Eliquis (apixaban) in patients with atrial fibrillation, whereas a previous trial of Eliquis in patients with ACS was halted due to an increased risk of bleeding.

In February, Astellas withdrew its Japanese filing for darexaban for the prevention of venous thromboembolism in at-risk patients, following a request from regulators to conduct more trials. The company has said it will decide on future plans for the drug based on the outcome of discussions with potential partners in the US and Europe.

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