AstraZeneca is voluntarily taking Andexxa off the US market, a year after the emergency reversal medication for factor Xa inhibitor anticoagulants was not fully approved by the FDA.

Andexxa (andexanet alfa) will no longer be commercially available, effective December 22. A spokesperson for the company told Medscape Medical News in an email that the Biologics License Application was being withdrawn for commercial reasons.

“In discussions with the FDA, alignment on a feasible path to convert Andexxa from accelerated to traditional approval in the US could not be reached. As agreed with the FDA, Andexxa will no longer be commercially sold,” she said.

Andexxa was first approved in 2018 under the FDA’s accelerated approval pathway based on effects in healthy volunteers. It was approved for the reversal of anticoagulation due to life-threatening or uncontrolled bleeding among patients treated with the factor Xa inhibitors rivaroxaban (Xarelto) or apixaban (Eliquis).

The ANNEXA-I clinical trial, published in 2024, found that treatment with Andexxa resulted in better control of hematoma expansion than usual care.

Thrombotic Event Association

But that trial was also associated with thrombotic events, including ischemic stroke. Just over 10% of Andexxa patients experienced at least one thrombotic event compared with 5.6% of those on usual care.

There was also an excess of ischemic strokes (6.5% vs 1.5%) and of myocardial infarction (4.2% vs 1.5%) in the Andexxa group, but no difference in deaths.

In 2024, Andexxa failed to secure full FDA approval after an advisory committee questioned whether ANNEXA-I’s primary endpoint of improvements in hemostatic efficacy at 12 hours was clinically relevant and whether it outweighed the safety concerns.

Concern for Patients

Ashkan Shoamanesh, MD, stroke neurologist at McMaster University in Hamilton, Ontario, Canada, and senior author on the ANNEXA-I trial, said the withdrawal leaves a major unmet medical need for patients who experience serious bleeds while taking direct oral anticoagulants.

“There is no other treatment for patients on factor Xa inhibitors that can rapidly reverse coagulation and has been proven to mitigate hematoma expansion in patients with acute ICH,” he said.

The current standard of care, against which Andexxa was measured, is prothrombin complex concentrate (PCC). But Shoamanesh said PCC has its own drawbacks in that it can also cause thrombotic events, and there are no conclusive data to indicate that it prevents hematoma expansion or rapidly reverses coagulation in this context.

“I have very little faith PCC provides much benefit in patients with acute FXa inhibitor-associated ICH but would not dissuade its use in the absence of an alternative treatment,” he said.

Shoamanesh believes it would have been better to keep Andexxa on the market and “allow physicians to make individualized decisions that could have reduced the risk of thrombosis and maximize benefit through careful patient selection.”

“From a patient perspective, this is not great news,” said Leslie Lake, volunteer president and board chair of the National Blood Clot Alliance. “There are still other options, such as PCC, but any time a medication is pulled from the market, it leaves a gap for patients.”

Lake criticized the lack of communication from AstraZeneca and the FDA on the drug’s withdrawal. “It happened quickly with little communication, and many patients haven’t been notified,” she said. “We’re now working to notify patients in our community.”

Shoamanesh reported receiving grants and consulting income from AstraZeneca, as well as VarmX, which is also developing a drug to reverse factor Xa inhibitors.

Brian Owens is a freelance journalist based in New Brunswick, Canada.