Bayer and partner Johnson & Johnson plan to advance the oral anticoagulant rivaroxaban into late-stage trials for the secondary prevention of acute coronary syndrome later this year after presenting promising Phase II data for the drug.

The ATLAS study, presented at the American Heart Association meeting in New Orleans, was designed to test the safety and efficacy of rivaroxaban, currently marketed as Xarelto in Europe for the prevention of venous thromboembolic events in adults who have undergone elective total hip or knee replacement surgery, at doses ranging from 5mg up to 20mg. Nearly 3,500 patients with ACS received standard antiplatelet therapy of low-dose aspirin with or without a thienopyridine, such as Sanofi-Aventis/ Bristol-Myers Squibb’s Plavix (clopidogrel) and were then randomised to additionally receive either Xarelto or a placebo for six months.

The study missed its primary endpoint as patients on Xarelto experienced a non-significant 21% relative risk reduction of death, myocardial infarction, stroke or severe recurrent ischaemia requiring revascularisation. However, ATLAS reached its secondary aim of with a significant 31% RRR against death, MI or stroke.

In terms of safety, as expected, rivaroxaban-treated patients exhibited higher rates of bleeding versus placebo and there was a significant dose trend. Nevertheless, no study arm was halted due to increased bleeding.

Though not statistically significant due to the small sample size, the two doses selected for Phase III – 2.5mg and 5mg dosed twice daily – showed the best balance between efficacy and safety with a 46% RRR in the composite efficacy endpoint of death, MI or stroke when dosed in addition to aspirin, and a 45% RRR in combination with aspirin and a thienopyridine.

Enrollment of up to 16,000 patients will begin next month for the late-stage study. Bayer expects Xarelto, a Factor Xa inhibitor, to achieve peak annual sales of more than 2 billion euros when all the possible indications, especially as a treatment for stroke in patients with atrial fibrillation, are approved.