Astrazeneca Anticoagulant Reversal Drug Pulled From U.S. Market

 Andexanet alfa (Andexxa) will officially be taken off the U.S. market this month as an emergency reversal medication for contemporary blood thinners.

"The Biologics License Application for Andexxa has been withdrawn for commercial reasons, effective December 22, 2025," a spokesperson from drugmaker AstraZeneca said in an email to MedPage Today.

To some, it may come as no surprise that andexanet is leaving the market, as the pricey direct oral anticoagulant (DOAC) antidote had been rejected for traditional FDA approval last year.

"In discussions with the FDA, alignment on a feasible path to convert Andexxa from accelerated to traditional approval in the U.S. could not be reached," AstraZeneca noted. "As agreed with the FDA, Andexxa will no longer be commercially sold by AstraZeneca in the U.S. after December 22, 2025."

In May 2018, andexanet was granted accelerated approval as the sole antidote on the market for the DOACs rivaroxaban (Xarelto) or apixaban (Eliquis). Its official indication was the reversal of anticoagulation due to life-threatening or uncontrolled bleeding among patients treated with these factor Xa inhibitors.

Approval was based an interim ANNEXA-4 analysis of the first 227 patients recruited who had developed acute major bleeding while on apixaban and rivaroxaban. In the full report of ANNEXA-4, one bolus of andexanet indeed resulted in a drastic drop in median anti-factor Xa activity: from 149.7 ng/mL to 11.1 ng/mL among apixaban users, and from 211.8 ng/mL to 14.2 ng/mL for the rivaroxaban cohort.

Andexanet also showed efficacy controlling hematoma volume change at 12 hours based on the ANNEXA-I trial of DOAC users with intracerebral hemorrhage.

Safety concerns arose as early as 2016's ANNEXA-4 initial study presentation, however, when outside observers noted a signal of excess thrombotic events among the study's andexanet users. The clotting issue became more apparent with ANNEXA-I showing more thrombotic events (14.6% vs 6.9%) and more thrombosis-related deaths (2.5% vs 0.9%) comparing andexanet versus usual care with a prothrombin complex concentrate (PCC).

A critical FDA advisory committee ensued, during which agency advisors discussed their reservations about which dose and in which patients andexanet could safely be used to stop bleeding.

Following andexanet's withdrawal, PCC remains available as the antidote for acquired coagulation factor deficiency in people on anticoagulation -- albeit specifically for vitamin K antagonist therapy such as warfarin.

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