AstraZeneca to Withdraw Andexxa in U.S. After FDA Finds Fatal Clot Risk
Post-marketing study revealed a more than twofold increase in thrombosis-related deaths, prompting the withdrawal of the bleeding-reversal agent acquired in a $1.4 billion deal.
AstraZeneca will pull its bleeding-reversal drug Andexxa from the U.S. market after regulators determined its risks, including a heightened danger of fatal blood clots, outweigh its benefits for patients.
The decision follows a review by the U.S. Food and Drug Administration (FDA) of new post-marketing safety data that revealed alarming safety signals. The ANNEXA-I trial, designed to confirm the drug's clinical benefit, showed patients treated with Andexxa experienced a thrombotic event rate of 14.6% within 30 days, more than double the 6.9% rate observed in patients receiving standard care. More critically, thrombosis-related deaths occurred in 2.5% of the Andexxa group, compared to just 0.9% in the control arm, according to a safety communication from the FDA.
In response to the findings, AstraZeneca announced it will discontinue all manufacturing, sales, and distribution of Andexxa in the United States, with a full market withdrawal planned by December 22, 2025.
Shares of AstraZeneca, trading on the Nasdaq, showed a muted reaction to the news in Tuesday morning trading, hovering around $91.50. The lack of a significant sell-off may reflect the drug's relatively small contribution to the pharmaceutical giant's vast portfolio and the extended timeline for its withdrawal. AstraZeneca currently boasts a market capitalization of over $283 billion.
Andexxa, known chemically as andexanet alfa, was designed as a crucial antidote for patients taking Factor Xa inhibitors—a popular class of blood thinners—who experience life-threatening bleeding. It received accelerated approval from the FDA in 2018, a pathway used for drugs addressing serious conditions with unmet medical needs, on the condition that further studies would verify its clinical efficacy and safety.
The withdrawal marks a costly end to the drug's U.S. commercial journey, which began with Portola Pharmaceuticals. In 2020, Alexion Pharmaceuticals acquired Portola for approximately $1.4 billion, largely to gain control of Andexxa. Just a year later, AstraZeneca acquired Alexion in a blockbuster $39 billion deal to bolster its rare disease pipeline, inheriting Andexxa in the process.
The FDA's decision did not come without warning. Earlier this year, the agency had rejected AstraZeneca's application to convert Andexxa's accelerated approval into a full, traditional approval, signaling underlying concerns with the drug's risk-benefit profile long before the final withdrawal decision.
In its statement, AstraZeneca cited the updated safety findings and subsequent discussions with the FDA as the basis for its decision. According to a report from Fierce Pharma, the company stated the withdrawal was for commercial reasons, a common framing for discontinuations prompted by insurmountable regulatory or safety hurdles.
The removal of a key reversal agent from the market presents a challenge for clinicians managing bleeding complications associated with some of the most widely prescribed anticoagulants. It also serves as a stark reminder of the risks inherent in the accelerated approval pathway, where initial promise must ultimately be confirmed by robust, long-term data.