Abelacimab Shows Unprecedented Bleeding Risk Reduction in Patients With Atrial Fibrillation

New data comparing abelacimab (MAA868) with rivaroxaban (Xarelto) in patients with atrial fibrillation were presented at the American College of Cardiology 2025 Annual Scientific Session. The American Journal of Managed Care^® spoke with AZALEA-TIMI 71 (NCT04755283) study investigator Christian T. Ruff, MD, MPH, director of General Cardiology at Brigham and Women’s Hospital; associate professor at Harvard Medical School; and senior investigator, TIMI Group.

The AZALEA-TIMI 71 trial evaluated the safety of the novel factor XI inhibitor abelacimab compared with rivaroxaban in patients with atrial fibrillation.¹ Among 1287 participants, nearly half were aged at least 75 years. Older patients had lower body mass index, were less likely to use antiplatelet therapy, and had higher rates of impaired renal function. Abelacimab significantly reduced the risk of major and clinically relevant non-major bleeding compared with rivaroxaban across all age groups, with a greater absolute risk reduction (ARR) in older patients (ARR, 7.1% with 90 mg and 6.2% for 150 mg) than in younger patients (ARR, 4.7% and 4.2%).

This transcript has been lightly edited; captions were auto-generated.

Transcript

Were there any unexpected findings in terms of bleeding risk reduction or patient subgroups that stood out in the AZALEA-TIMI 71 trial?

I think the only thing that stands out is just the magnitude of the benefit. I mean, we all thought abelacimab and factor XI inhibition, in general, would be safer. ...I did not anticipate it would be this much safer. We would have been excited to see a 30% reduction in bleeding, but to see a 60% to 70% reduction in bleeding, almost eliminating gastrointestinal bleeding, that was greater than anticipated.

What is also surprising has been just the consistency of that benefit. And so we looked hard to say, "Well, maybe that benefit isn't in the highest-risk patients; maybe it's not being elderly; maybe it's not patients who are on antiplatelet therapy; maybe it's not patients at the very high risk of bleeding." But we see—what's remarkable—is just how persistent that benefit is. And I think that that's reassuring, that I don't care how high risk your patient is, abelacimab is incredibly safe, and so we think obviously, if shown to be effective in phase 3 trials, that would just be a tremendous advantage for the field.

How do you see these results influencing clinical guidelines or physician decision-making for anticoagulation?

We know that the decision to anticoagulate, in general, or the decision [of] which anticoagulant you prescribe or you're willing to take is driven in large part by [the] safety of the drugs. People know they're effective; the reason they don't take them or don't prescribe them is because they think the bleeding risk is too high, and we've been fighting that battle for many decades. I think that if you delivered effective therapy, people are going to use the safest drug because bleeding is a big issue. It has very adverse consequences downstream, and it leads to drug discontinuation. I think if abelacimab is approved, given its remarkable safety, there'll be tremendous enthusiasm to use it, and it'll be warranted because having an effective drug that's safe—that's the therapy we should be using.

Obviously, the demonstration of efficacy requires the phase 3 studies, which are powered and designed to prove that these drugs are as effective as either standard of care or in an unmet need. Those results are ongoing, but if those phase 3 trials confirm the efficacy of abelacimab, we believe that this would be practice-changing, not just in guidelines, but would be widely embraced by the clinical community.

Reference

Al Said S, Patel SM, Giugliano RP, et al. Bleeding with the FXI inhibitor abelacimab compared with rivaroxaban in older individuals with atrial fibrillation: analysis of the AZALEA-TIMI 71 trial. Paper presented at: American College of Cardiology 2025 Annual Scientific Session; March 29-31, 2025. Chicago, Illinois. Session 939-19.