The first NEJM publication regarding andexanet featured just the first 67 patients from ANNEXA-4, an open-label, single-arm descriptive study of patients given andexanet for major bleeding. And, it all vanishes to dust when the infusion completes. A bolus and infusion that costs ~$3,000 per 100mg vial – and requires 900mg for a “low dose” protocol or 1,800mg for a “high dose” protocol. This necessitates a bolus and an infusion. The half-life of andexanet is approximately 1 hour, after which point the factor Xa inhibitor levels rise and hemostasis is again impaired.

The problem, however, is the reversal is not durable. When sufficient Xa inhibitor is bound to andexanet, the native version is freed to return to its normal work in hemostasis. The mechanism of action is simple: andexanet mimics native factor Xa, providing the various Xa inhibitors (rivaroxaban, apixaban, edoxiban, betrixiban, and enoxaparin) an alternative target. About two and a half years ago, we were introduced to andexanet alfa (Andexxa), a modified recombinant form of factor Xa designed as a reversal option for factor Xa inhibitors.

Andexanet alfa mechanism of action