An interim analysis from the ongoing ANNEXA-4 study has shown that the experimental reversal agent andexanet was associated with a reduction in anti-Factor Xa inhibitor activity and control of bleeding, according to a Featured Clinical Research presentation on Monday, March 12 at ACC.18 in Orlando, FL.

Led by Stuart Connolly, MD, researchers assessed the efficacy of this first-in-class drug in terms of two co-primary endpoints – reduction in anti-Factor Xa inhibitor activity and achievement of clinical hemostasis within 12 hours of administration. The interim data on safety outcomes for 227 patients and adjudicated efficacy outcomes for 132 patients enrolled at centers in the U.S., Canada and Europe were presented. All study patients presented with acute major bleeding within 18 hours of taking one of four Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban or enoxaparin). They received an injection of andexanet followed by a two-hour infusion of the drug, with the dose determined based on the specific Factor Xa inhibitor the patient was taking and the time since the last dose.

There was a median reduction in anti-Factor Xa inhibitor activity of 88 percent for patients taking rivaroxaban, 91 percent for patients taking apixaban and 75 percent for patients taking enoxaparin. Very few patients in the study had received edoxaban. Excellent or good clinical hemostasis was achieved in 83 percent of patients. Safety of andexanet was assessed in all 227 patients. At 30 days, 12 percent of patients had died and 11 percent had a thrombotic event.

According to Connolly, the rates of death and thrombotic events are consistent with expectations given the high-risk profile of the patients. If approved by the U.S. Food and Drug Administration, andexanet would be the first agent to directly reverse the effects of bleeding associated with Factor Xa inhibitors. "Factor Xa inhibitors are already widely used because of their excellent efficacy and safety profile," Connolly said. "However, some physicians and patients may choose to use other anticoagulant drugs because they have a reversal agent rather than using one of the Factor Xa inhibitors. Having a safe and effective reversal agent available will benefit patients with acute bleeding."

Keywords: ACC18, ACC Annual Scientific Session, Aneurysm, Enoxaparin, Coronary Artery Disease, Atrial Fibrillation, Confidence Intervals, Pyridones, Factor Xa, Pyrazoles, Pyridines, Recombinant Proteins, Thiazoles, Hemostasis, Venous Thrombosis, Anticoagulants

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