Andexxa Blood Clot Risks Lead to FDA Questions Regarding Safety of the Reversal Agent for Xarelto, Eliquis

FDA researchers indicate that individuals given Andexxa during a clinical trial were also more than twice as likely to die than those treated by other means.

A panel of scientific advisors to the FDA is meeting today to discuss potential safety problems linked to Andexxa, which was introduced to the market six years ago to reverse the blood thinning effects of Xarelto, Eliquis and similar drugs, helping avoid uncontrolled bleeding problems linked to the widely used anticoagulants.

FDA advisory committees are made up of independent experts who are convened to review the safety and effectiveness of prescription medications, and make recommendations to the agency regarding different regulatory actions. While recommendations made by the committees are not binding, the FDA usually follows their advice.

The U.S. Food and Drug Administration (FDA) Cellular, Tissue and Gene Therapies Advisory Committee is scheduled to review the safety and efficacy of the reversal agent, including concerns about potential Andexxa blood clot risks. However, this panel is not expected to vote on any specific recommendations.

Questions about Andexxa Risks and Benefits

The FDA first approved Andexxa (andexanet) in 2018, to address problems with uncontrollable bleeding events linked to a new generation of direct oral anticoagulants, including Xarelto and Eliquis. Unlike their older predecessor warfarin, these drugs’ blood thinning effects could not be stopped through the use of vitamin K, and doctors often found themselves in situations where they could not prevent patients from bleeding out.

However, as part of the accelerated process, the FDA called on the manufacturer, AstraZeneca, to conduct a postmarketing confirmatory study known as the ANNEXA-1 trial. With the completion of that trial, AstraZeneca is now asking for the drug to be granted full approval.

Ahead of the FDA panel meeting scheduled for today, the agency has released a briefing document, which raises concerns that Andexxa may double the risk of dangerous blood clots.

The ANNEXA-1 trial consisted of 404 patients, with 204 given Andexxa for bleeds experienced while on a Factor Xa blood thinner, such as Xarelto and Eliquis, and 200 treated with usual care (UC) without the reversal agent.

According to the FDA briefing document, results from the ANNEXA-1 trial indicate the risk of thrombosis, or blood clots, was 14.6% for patients on Andexxa, which is more than double the 6.9% of patients who experienced clotting after receiving standard medical care. The researchers also noted that Andexxa patients were more than twice as likely to die than those given standard care, with 2.5% of patients dying on the Andexxa side of the trial, compared to just 0.9% treated via standard care.

“The major safety findings included a doubling of the rate of thromboses and thrombosis-related deaths at Day 30 in the Andexanet arm compared with UC,” FDA investigators wrote. “These findings raise concerns regarding whether the serious risks of treatment with [Andexxa] are acceptable in the indicated population.”

The clinical trial results indicated that Andexxa did meet one of its goals of preventing dangerous brain bleeds. However, that was only one of three primary endpoints researchers were looking for.

According to the FDA’s analysis, Andexxa use showed no signs of improving neurologic status within 24 hours, or cutting overall mortality when compared to the standard treatments, which were the other two benchmarks of the study.