Currently, millions of patients are treated with Factor Xa inhibitors for short-term use or chronic conditions. Based on data from large Phase 3 trials, approximately 1% to 3% of patients taking an oral Factor Xa inhibitor experience a major bleed, and another 1% of patients require emergency surgery. This bleeding is associated with an increased risk of death.
In the U.S., more than 90,000 patients treated with oral Factor Xa inhibitors were admitted to the hospital due to bleeding during 2016. Including patients taking the injectable Factor Xa inhibitor enoxaparin, it is estimated that more than 150,000 U.S. patients could benefit from an antidote annually.
Andexanet alfa is a modified human protein specifically designed to reverse the anticoagulant activity of both direct and indirect Factor Xa inhibitors. Once bound by andexanet alfa, the Factor Xa inhibitors are unable to bind and inhibit native Factor Xa, thus potentially allowing for the restoration of normal hemostatic processes. It is being developed to address major and sometimes fatal bleeding associated with Factor Xa inhibitors. The U.S. FDA has granted Breakthrough Therapy designation to andexanet alfa.
Andexanet alfa currently is being studied in ANNEXA-4 (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors), a Phase 3b/4 single-arm, open-label confirmatory study in patients who present with an acute major bleed while receiving the Factor Xa inhibitors apixaban, rivaroxaban, edoxaban or enoxaparin (a low molecular weight heparin and indirect Factor Xa inhibitor). The co-primary efficacy endpoints are the percent change in anti-Factor Xa activity at 2 hours and assessment of hemostasis over 12 hours following the infusion.
In August 2016, we announced a descriptive preliminary analysis from the ANNEXA-4 trial, showing andexanet alfa rapidly and substantially reversed anti-Factor Xa activity, and these levels were sustained for the duration of administration. An independent adjudication committee determined that 37 of 47 patients (79%) achieved excellent or good hemostasis.