AstraZeneca Withdraws Andexxa After FDA Finds Safety Risks for Patients

AstraZeneca announced that it will withdraw Andexxa, the recombinant factor Xa reversal agent, from the U.S. market following an updated safety determination by the Food and Drug Administration. The company ceased commercial sales and U.S. manufacture of Andexxa on December 22, 2025 after the FDA on December 18 concluded that postmarketing data and the results of a required confirmatory trial showed thromboembolic events including serious and fatal outcomes, and that the known risks outweigh the drug’s benefits for its approved indication.

Andexxa, or andexanet alfa, had been approved in 2018 under the accelerated approval pathway to reverse anticoagulation caused by rivaroxaban and apixaban in patients with life threatening or uncontrolled bleeding. The approval required AstraZeneca to complete a randomized confirmatory trial. That study, ANNEXA I, ClinicalTrials.gov identifier NCT03661528, enrolled patients with intracerebral hemorrhage who had been treated with rivaroxaban or apixaban and compared Andexxa with usual care.

In regulatory filings and agency summaries the FDA reported that ANNEXA I showed a roughly doubled rate of thromboses and thrombosis related deaths at 30 days in the Andexxa arm compared with usual care. Those findings, together with additional postmarketing safety reports, underpinned the agency’s decision not to convert the accelerated approval to full approval in December 2024 and led to the December 2025 safety communication that precipitated the company’s voluntary withdrawal of the Biologics License Application.

The U.S. label for Andexxa had carried a boxed warning for thromboembolic events while the product was on the market. The withdrawal means that, effective December 22, clinicians in the United States will no longer have an FDA approved, product specific option to reverse factor Xa inhibitors. Emergency management of major bleeding in patients on rivaroxaban or apixaban will rely on existing supportive measures and institutional protocols, and clinicians and hospitals will need to reassess local treatment pathways in the absence of Andexxa.

AstraZeneca acquired the product through corporate transactions that began with Portola Pharmaceuticals, which won accelerated approval in 2018, followed by Alexion’s purchase of Portola, and AstraZeneca’s later acquisition of Alexion. The product’s commercial footprint had been modest relative to larger branded drugs, with reported full year Andexxa sales of about $219 million last year.

The withdrawal highlights growing scrutiny of accelerated approvals that are contingent on postmarket confirmatory studies. Regulators and clinicians have long debated the balance of giving patients access to emergency therapies while ensuring robust evidence of safety and efficacy. In this case the FDA concluded that the postmarketing safety profile and the ANNEXA I results demonstrated excess harm.

For patients and clinicians the immediate questions will center on how to manage life threatening bleeds in the absence of an approved reversal agent, and on how hospitals will adapt protocols that had incorporated Andexxa. For regulators and drug developers the episode underscores the consequences when confirmatory trials fail to confirm initial expectations for therapies approved under accelerated pathways.