Andexanet Alfa Pulled From US Market

After today, andexanet alfa (Andexxa; AstraZeneca) will no longer be made or sold in the United States, according to an alert from the US Food and Drug Administration.

The agency updated a safety communication last week indicating the risks of using andexanet alfa—which reverses the anticoagulant effects of the factor Xa inhibitors rivaroxaban (Xarelto; Bayer/Janssen) and apixaban (Eliquis; Bristol-Myers Squibb)—outweigh the potential benefits based on an analysis of thromboembolic events from postmarketing data.

“The FDA has communicated this position to AstraZeneca, and the company has submitted a request to voluntarily withdraw the [biologics licensing application] for the product for commercial reasons,” the agency said.

Andexanet alfa initially received accelerated approval from the FDA in 2018 for patients treated with rivaroxaban or apixaban who required a reversal of anticoagulation due to life-threatening or uncontrolled bleeding based on evidence showing efficacy in healthy volunteers and preliminary data from the ANNEXA-4 trial. The approved label contained a boxed warning on risks of thromboembolic events, cardiac arrest, and sudden death.

With the approval, the FDA required a randomized trial to confirm the clinical benefits of andexanet alfa in patients with intracerebral hemorrhage while being treated with rivaroxaban or apixaban, with the ANNEXA-I trial fulfilling this mandate. When discussing the results, an FDA advisory committee mulled a doubling in the rates of thrombosis (14.6% vs 6.9%) and thrombosis-related deaths (2.5% vs 0.9%) at 30 days in patients treated with the reversal agent versus usual care.

It remains unclear how andexanet alfa will be handled in other markets outside the US. For now, an AstraZeneca spokesperson told TCTMD in an emailed statement, “Andexxa is conditionally approved in Europe and approved in the United Kingdom and other countries like Japan where it is currently available under the brand name Ondexxya. . . . The decision to withdraw is contained to the US and Andexxa is available to patients around the world, in line with local regulations.”