The FDA announced that postmarketing safety data on Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo) have revealed an increased risk of thromboembolic events, including serious and fatal outcomes, among treated patients. Based on these findings, the agency determined that the risks associated with Andexxa outweigh its benefits.
The FDA has communicated this assessment to AstraZeneca, the product’s manufacturer. In response, AstraZeneca has voluntarily requested withdrawal of the biologics license application (BLA) for commercial reasons and confirmed plans to end U.S. commercial sales of Andexxa by December 22, 2025. After that date, the product will no longer be manufactured or distributed in the United States.
The FDA emphasized that ongoing monitoring and safety evaluation of all biological products, including Andexxa, remain a top agency priority. The agency reaffirmed its commitment to keeping the public informed when new safety data emerge.
Background
Andexxa received accelerated approval (AA) in 2018 as a recombinant modified human factor Xa (FXa) protein, indicated for patients treated with rivaroxaban or apixaban when reversal of anticoagulation is required due to life-threatening or uncontrolled bleeding. The initial approval included a boxed warning for thromboembolic risks. Accelerated approval was granted based on changes from baseline in anti-activated FXa (anti-FXa) activity in healthy volunteers, a surrogate endpoint considered reasonably likely to predict clinical benefit.
As part of the accelerated approval requirements, AstraZeneca was obligated to conduct a randomized controlled trial (NCT03661528) to verify the product’s clinical benefit in patients with intracerebral hemorrhage following treatment with rivaroxaban or apixaban. On January 31, 2024, AstraZeneca submitted a supplemental Biologics License Application (sBLA) including results from the ANNEXA-I trial to fulfill this requirement.
On November 21, 2024, the Cellular, Tissue, and Gene Therapies Advisory Committee (AC) met to review the ANNEXA-I data. The committee discussed significant safety findings, including a doubling of thrombosis rates and thrombosis-related deaths at 30 days in the Andexxa arm compared with usual care. Specifically, the trial showed a higher incidence of thrombosis (14.6% vs. 6.9%) and thrombosis-related deaths at Day 30 (2.5% vs. 0.9%) among patients receiving Andexxa. Of the 35 Andexxa-treated patients who experienced thrombotic events, more than half (53%) had early-onset events compared with approximately 6% in the usual care group.
The FDA stated it will continue working with AstraZeneca to provide healthcare providers and the public with updates as the company concludes Andexxa’s commercial availability in the U.S.
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