FDA Rejects Full Approval for AstraZeneca’s Andexxa Amid Safety Concerns

Background:
Andexxa (andexanet alfa) is a recombinant protein designed to reverse the anticoagulant effects of direct oral Factor Xa (FXa) inhibitors, such as apixaban and rivaroxaban, in cases of life-threatening or uncontrolled bleeding1 2.

Accelerated Approval:
Andexxa received accelerated approval from the FDA in 2018 based on a surrogate endpoint, with a requirement for a postmarketing study (ANNEXA-I) to confirm its clinical benefit1 5.

ANNEXA-I Trial:
The ANNEXA-I trial was stopped early after achieving pre-specified criteria for superior haemostatic efficacy compared to usual care. However, the trial also showed an increased risk of thrombosis and thrombosis-related deaths in the andexanet arm1 2.

FDA Concerns:
The FDA has raised safety questions regarding the increased risk of thrombosis associated with Andexxa, leading to a rejection of full approval. The agency is seeking further discussion on the benefits and risks of the treatment1 4.

Current Status:
The fate of Andexxa is unclear, with ongoing discussions between AstraZeneca and the FDA. The drug will remain on the US market while these discussions continue3.