As a council of outside experts prepares to meet Thursday to discuss AstraZeneca’s Andexxa, the FDA has flagged “major safety findings” linked to the British drugmaker’s bleeding reversal agent.
At this week’s meeting of the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee, panelists will be tasked with debating two questions around Andexxa’s safety and efficacy, leveraging data from a confirmatory trial.
Andexxa, which won an accelerated approval back in 2018, is a recombinant protein that binds to factor Xa inhibitors to reverse their anticoagulant effects. While factor Xa inhibitors are used to manage clots, the class of blood thinners carries a small but serious risk of severe bleeds, prompting then need for specialized reversal agents like Andexxa.
The FDA is calling the advisory committee meeting as AstraZeneca jockeys for a full approval for its med using data from the postmarketing ANNEXA-I trial. While the experts at the meeting are expected to discuss Andexxa’s efficacy and safety record, they won’t be voting on a specific recommendation for the FDA.
Companies that win accelerated nods from the FDA must run additional studies to prove their drugs’ merits, which the regulator can then weigh when deciding whether to grant a full, traditional approval.
In outlining the main topics of the discussion in a briefing document filed this week, the FDA noted that AZ’s data have revealed “major safety findings” related to Andexxa. Namely, the rate of thrombosis, or clotting, for patients on Andexxa doubled at 14.6% in the study versus just 6.9% in patients who received standard care.
In turn, the panelists are expected to hash out whether the “serious risks of andexanet” are acceptable and commensurate to the benefit seen in ANNEXA-I, the FDA said, referring to Andexxa by its generic name.
Additionally, the experts will talk through the nature of how Andexxa hit the primary endpoint in its confirmatory trial and whether that result constitutes a clinical benefit.
Last June, AstraZeneca halted its post-marketing study on the advice of a data monitoring board after the trial showed that patients on Andexxa experienced superior hemostatic efficacy—or the body’s ability to stop the flow of life-threatening brain bleeds—versus standard-care treatment.
While Andexxa met the primary goal of ANEXXA-I, that result “appears to be primarily driven by” hematoma volume at 12 hours, which was one component of a three-party composite endpoint, the FDA pointed out in its briefing document. Other endpoints, such as neurologic status at 24 hours and overall mortality, “were not different” between the study’s Andexxa and control arms, the regulator added.
Andexxa was one of the many products AstraZeneca acquired in its $39 billion buyout of Alexion in late 2020. Alexion, for its part, originally got its hands on the bleeding reversal agent through its own $1.4 billion acquisition of Portola Pharmaceuticals.
For all of 2023, Andexxa brought home (PDF) $182 million in sales, growing 23% at constant currencies over the $150 million it generated in 2022.