FDA experts lukewarm on AZ's anticoagulant antidote Andexxa
AstraZeneca's anticoagulant reversal agent Andexxa was given an accelerated approval by the FDA in 2018, but the company's plan to get that upgraded to a full approval is facing some pushback.
At an FDA advisory committee meeting yesterday, experts didn't actually vote on whether full approval should be granted, but spent the time debating the results of the supporting ANNEXA-I trial and whether they could be considered clinically meaningful.
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.
On the positive side, members of the Cellular, Tissue, and Gene Therapies Advisory Committee agreed that Andexxa was able to prevent the expansion of the volume of haematoma – blood that forms outside a blood vessel – 12 hours after administration of AZ's drug to patients experiencing an intracerebral haemorrhage after anticoagulation. The haematoma volume was measured using MRI.
However, they were uncertain whether that surrogate marker result translated into a clinical benefit, for example improved neurological status or survival, while there were risks associated with Andexxa, including higher rates of thromboses and clot-related deaths compared to standard care with prothrombin complex concentrate (PCC) in the trial.
At 30 days, 14.6% of participants receiving Andexxa logged thrombotic events, compared with 6.9% in the control group, with clot-related deaths at 2.5% and 0.9%, respectively.
The 450-subject ANNEXA-I study was stopped early last year after the drug achieved the pre-specified criteria of superior haemostatic efficacy – limiting the expansion of a potentially life-threatening bleed in the brain – compared to standard care.
The absence of any formal vote on the drug leaves the FDA with a tricky decision to make as it heads for the completion of its review of the application – filed in January – within the next few weeks. And the panel's cool reception has raised speculation that the regulatory may ask for additional clinical evidence before it will consider concerting the approval.
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 makes relatively modest sales – rising 26% to $159 million in the first nine months of the year – but remains the only Factor Xa reversal agent on the market.
Some panellists pointed out that PCC is unapproved and known to have limited efficacy, so keeping the only approved therapy on the market makes sense, even if the FDA asks for additional data.
Image by Mohamed Hassan from Pixabay
