Results from a late stage trial of an investigational drug showed promising results for reversing anticoagulation in Factor Xa-associated bleeding.
Based on results presented at the American College of Cardiology’s 67th Annual Scientific Session and Expo, the investigational drug AndexXa (andexanet alfa, Portola Pharmaceuticals) rapidly reversed anti-Factor Xa activity when administered as a bolus, and sustained this reversal when followed by a 120-minute infusion, in. Andexanet alfa is a universal Factor Xa inhibitor antidote.
Interim data from its Phase 3b/4 trial of AndexXa, also found that 83% of patients treated with andexanet alfa achieved excellent or good hemostasis over a 12-hour period following treatment, according to a statement from Portola.
“These data are particularly compelling when you consider the high-risk profile of the ANNEXA-4 population,” said Stuart J. Connolly, MD, ANNEXA-4 Executive Committee chairman and professor of medicine at McMaster University, Hamilton, Ontario. The study population included a substantial number of elderly patients presenting with intracranial hemorrhage and anticoagulated for venous thromboembolism. There is no FDA- or EMA [European Medicines Agency]-approved reversal agent for these patients, he notes. “The interim efficacy and safety data continue to support the promising role of AndexXa as an antidote to reverse anticoagulation in Factor Xa-associated bleeding.”
The use of Factor Xa inhibitors is continuing to grow at a significant pace because of their demonstrated efficacy in preventing embolic diseases, such as stroke and pulmonary embolism, according to Portola. “However, the incidence of hospital admissions and death related to Factor Xa-inhibitor bleeding is also increasing. In the U.S. alone, there were approximately 117,000 hospital admissions attributable to Factor Xa-related bleeding in 2016 and more than 2,000 bleeding-related deaths per month,” according to Portola.
The interim results included safety data from 227 of the 228 enrolled patients who experienced intracranial hemorrhage (61%), gastrointestinal bleeding (27%) or bleeding from another site (11%) within 18 hours of administration of apixaban (Eliquis), rivaroxaban (Xarelto), enoxaparin (Lovenox), or edoxaban (Lixiana).
During the 30-day follow-up period, the thrombotic event rate was 11% for the entire population and 12% among patients experiencing an intracranial hemorrhage. The mortality rate for all patients was 12%. “The rate of these events occurred within the range expected in this population given the severity of the bleeding, their advanced age, and underlying thrombotic risk, and the percentage who restarted anticoagulant therapy (57%) following their bleeding episode,” Portola says.
In addition, thrombotic events and death rates were consistent with previous ANNEXA-4 trial results and with the high thrombotic risk of the enrolled patient population.