After nearly two years rife with rejections and requests for more information, Portola Pharmaceuticals’ AndexXa has been approved by the Food and Drug Administration (FDA), as the only antidote to reverse the blood thinning effects of the Factor Xa inhibitor anticoagulants Xarelto and Eliquis, in cases of life-threatening or uncontrolled bleeding.
Xarelto and Eliquis work by inhibiting a protein involved in the formation of blood clots. They are used to prevent strokes in patients with the common heart rhythm abnormality atrial fibrillation, to prevent and treat deep vein thrombosis and pulmonary embolism, and to prevent blood clots in patients who have recently undergone hip or knee replacement surgery.
Xarelto and Eliquis were approved in 2011 and 2012, respectively, and were designed to be more convenient alternatives to the long-used warfarin, which requires patients to be regularly monitored. But unlike warfarin, there was not an antidote available to reverse the blood thinning effects of the drugs in the event of a bleeding emergency or uncontrolled bleeding.
AndexXa, known chemically as andexanet, has been repeatedly rejected by the FDA because more data was needed. The FDA was scheduled to make its decision last February but pushed the date back to May for further review, even suggesting it may call for more test before clearance could comfortably be granted.
The antidote is a much-anticipated therapy. Xarelto has been linked to serious bleeding events including gastrointestinal bleeds and brain bleeds. Its manufacturers, Johnson & Johnson’s Janssen Pharmaceuticals and Bayer, face about 20,000 lawsuits alleging the company did not adequately warn of Xarelto bleeding risks, and negligently marketed the drug without a reversal agent.