Andexxa reaches the end of the line in the US

AstraZeneca will voluntarily take its anticoagulant reversal agent Andexxa off the market in the US in light of FDA concerns over clotting complications – including deaths – in people taking the drug.

The decision comes just over a year after it failed to convince the US regulator to upgrade an accelerated approval for the drug – awarded in 2018 – into a full approval on the strength of the ANNEXA-I trial.

Andexxa (andexanet alfa) is approved for the reversal of anticoagulation by Factor Xa inhibitors – Bayer/Johnson & Johnson's Xarelto (rivaroxaban) and Pfizer/Bristol-Myers Squibb's Eliquis (apixaban) – if treatment with the drugs leads to life-threatening or uncontrolled bleeding complications. Its label already includes a boxed warning for thromboembolic risks.

According to an FDA update, there have been "postmarketing safety data on thromboembolic events, including serious and fatal outcomes, in patients treated with Andexxa," and it now considers that "the risks of the product…outweigh its benefits."

The agency added that AZ will end commercial sales of the drug today (22nd December) and has submitted a request to voluntarily withdraw the product for commercial reasons.

In ANNEXA-I, there was a doubling of the rate of thromboses and thrombosis-related deaths at 30 days in the Andexxa arm compared with usual care, according to an FDA alert.

AZ acquired rights to Andexxa through its $39 billion takeover in 2021 of Alexion, which in turn claimed ownership when it bought Portola Pharma in 2020 for $1.4 billion.

The drug – which is a modified, inactive recombinant human factor Xa protein and acts as a decoy for inhibitors – was the first and only specific antidote to be launched in the US, but failed to gain much traction in the marketplace.

Sales reached approximately $220 million globally last year, of which around $80 million came from the US, but AZ has latterly stopped mentioning its performance in its quarterly financial reporting. After its accelerated approval, some analysts were predicting that peak sales could reach upwards of $1 billion a year.

Withdrawal does not leave patients without any options, as alternatives are available, specifically prothrombin complex concentrates (PCCs), although these are not FDA-approved and have limited efficacy.