ANDEXXA Rx

The approval of Andexxa was based on two phase 3 studies (Study 1 ANNEXA-A; Study 2 ANNEXA-R), which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of rivaroxaban and apixaban in healthy participants. Both studies evaluated the percent change in anti-FXa activity, from baseline to nadir, for the low-dose and high-dose regimens of bolus followed by continuous infusion.

In addition, the FDA reviewed interim data from  a single-arm, open-label study (Study 3 ANNEXA-4) in patients with major bleeding and who have recently received an FXa inhibitor. This study evaluated the percent change in anti-FXa activity from baseline to the nadir between 5 minutes after the end of the bolus up until the end of the infusion and the rate of effective hemostasis within 12 hours after infusion.

In Study 1 and 2, results showed that Andexxa quickly and significantly reversed anti-Factor Xa activity. In Study 1, the mean percent change in anti-FXa activity from baseline at the nadir was -92.3% for Andexxa vs -32.7% for placebo (difference -59.5%; 95% CI, -64.1, -55.2; P <.0001). In Study 2, the mean percent change in anti-FXa activity from baseline at the nadir was -96.7% for Andexxa vs -44.6% for placebo (difference -51.9%; 95% CI, -58.0, -47.0; P <.0001). 

In Study 3, the median decrease in anti-FXa activity from baseline to nadir for apixaban was -93% with a 95% CI of (-94%; -92%) and for rivaroxaban was -93% with a 95% CI of (-94%; -90%). An improvement in hemostasis has not been established. Andexxa has not been shown to be effective for bleeding related to any FXa inhibitors other than apixaban or rivaroxaban.