Bayer’s rivaroxaban granted Priority Review by US FDA to prevent secondary cardiovascular events in patients with acute coronary syndrome


The US Food and Drug Administration (FDA) has granted Priority Review designation to the supplemental New Drug Application (sNDA) for rivaroxaban (Xarelto, Bayer) in combination with standard antiplatelet therapy to reduce the risk of (thrombotic) cardiovascular events in patients with acute coronary syndrome. The application was filed on 29 December 2011.


The FDA grants Priority Review to medicines that offer advances in care or that provide a treatment where no adequate therapy exists. Under the Prescription Drug User Fee Act (PDUFA), FDA will complete its review within six months from the receipt of the sNDA submission.


“Acute coronary syndromes represent a huge burden to UK patients and the NHS. Alternative oral anticoagulation therapies which can improve survival in this patient group are vitally important” said Mark de Belder, consultant cardiologist at The James Cook University Hospital in Middlesbrough and former president of the British Cardiovascular Intervention Society.


The submission was based upon data from the pivotal, global Phase III ATLAS ACS 2-TIMI 51 study. Results from the study, presented at the 2011 American Heart Association Scientific Sessions and simultaneously published by the New England Journal of Medicine, demonstrated that patients dosed with 2.5 mg BID of rivaroxaban showed a significant reduction in risk of the composite primary endpoint [9.1% vs. 10.7% (P=0.020)], driven by a significant 34% RRR in the rate of cardiovascular death and an absolute reduction of 1.4% [2.7% vs. 4.1% (P=0.002)]. There was also a 32% risk reduction [1.6% ARR] in deaths from any cause [2.9% vs. 4.5% (P=0.002)]. Furthermore, rivaroxaban reduced stent thrombosis by 31% (0.6% ARR). The number of patients needed to treat (NNT) was 59 to prevent cardiovascular death and 56 to prevent all-cause mortality.


The principal safety endpoint for the study was TIMI major bleeding not associated with coronary artery bypass graft (CABG) surgery. In patients receiving rivaroxaban in combination with standard antiplatelet therapy, bleeding rates were statistically significantly increased versus those treated with standard antiplatelet therapy plus placebo [2.1% vs. 0.6% (P<0.001)]. Similarly, rivaroxaban (2.5mg BID) resulted in higher rates of TIMI major bleeding events not associated with CABG surgery compared to placebo [1.8% vs. 0.6% (P<0.001)]. Importantly, rivaroxaban (2.5mg BID) did not increase the risk of fatal bleeding. Other treatment-emergent adverse events were balanced across treatment groups.