Days after US regulators turned down their bid to expand the label on Xarelto to include the reduction of the risk of cardiovascular events in acute coronary syndrome patients, Bayer and Johnson & Johnson have unveiled a number of studies designed to look at other indications for the bloodthinner.
First up, a Phase III study has been initiated with Xarelto (rivaroxaban) in patients with chronic heart failure and significant coronary artery disease (CAD). Bayer noted that it is the first novel oral anticoagulant to be evaluated in this patient group who remain at high-risk for complications following hospitalisation; in the USA and Europe, three-quarters of all patients hospitalised with heart failure for the first time will die within five years, the firm noted.
The trial, called COMMANDER-HF, will assess 2.5mg twice-daily Xarelto compared to placebo (on top of standard treatment) in reducing the risk of death, myocardial infarction or stroke in 5,000 patients with chronic HF and significant CAD following hospitalisation. The US Food and Drug Administration has granted a fast-track designation for the study, speeding up the review of low-dose rivaroxaban in this indication.
Another late-stage trial, PIONEER AF-PCI, will evaluate Xarelto in 2,100 patients who have non-valvular atrial fibrillation and are undergoing percutaneous coronary intervention with stent placement. The study is looking at Xarelto in combination with dual antiplatelet therapy and when aspirin is not used.
J&J noted that the two Phase III studies are part of the five-trial EXPLORER programme. As for the others, COMPASS is looking at Xarelto in 20,000 patients with CAD or peripheral artery disease, while X-VeRT is evaluating 1,500 patients with AF scheduled for cardioversion, a procedure to convert abnormally fast heart rate to a normal rhythm. The VENTURE-AF study will investigate Xarelto in up to 250 patients with non-valvular AF undergoing catheter ablation.
Xarelto is approved for six uses already in the USA - reducing the risk of strokes in patients with nonvalvular AF, as a treatment for deep vein thrombosis and pulmonary embolism and for reducing the risk of blood clots in the legs and lungs of people who have had hip or knee replacement surgery.
However, last week the FDA issued a second complete response letter to Bayer and J&J's request to market Xarelto for the reduction of the risk of cardiovascular events in patients with ACS. The agency first rejected a supplemental New Drug Application in June last year, citing concerns over bleeding.