Interpreting the Clinical Benefit of Abelacimab for Atrial Fibrillation, with Christian Ruff, MD, MPH

Results from the phase 2 AZALEA-TIMI 71 trial showed abelacimab, a factor XI inhibitor, significantly reduced bleeding and was well-tolerated in patients with atrial fibrillation (AF) at risk of stroke, compared to the standard-of-care, rivaroxaban.¹

Presented at the American Heart Association (AHA) Scientific Sessions 2023 in Philadelphia, Pennsylvania, the late-breaking data showed a reduction of ≥60% in major bleeding among patients with AF taking abelacimab, either 90 mg or 150 mg monthly doses, compared with 20 mg daily rivaroxaban.

In an interview with HCPLive, study author Christian T. Ruff, MD, MPH, the director of general cardiology at Brigham and Women’s Hospital and senior investigator for the TIMI Group, described the need for new antithrombotic therapies, and the net clinical benefit outcome of abelacimab for AF.

“Both abelacimab arms, for the total net clinical outcome, highly significantly reduced the outcome by 51%,” Ruff said. “In this trial, if you look at what you are trying to accomplish, you want to prevent strokes, cause very low rates of bleeding, and you want that patient to be alive to see you in the clinic in 6 months. There’s a 50% reduction in those bad things happening in the abelacimab arms compared to rivaroxaban.”

AZALEA-TIMI 71 enrolled 1,287 adults, including 44% women, across 95 global study sites between March - December 2021, with a median follow-up time of nearly 2 years. Participants were ≥55 years old, had a history of AF and anticoagulants, and were considered at a moderate to high risk of stroke, as determined by CHA2DS2-VASc scores.

This trial was noted as the longest and largest trial comparing factor XI inhibitors to the current standard-of-care use of direct-acting oral anticoagulants. Upon analysis, investigators found abelacimab reduced major bleeding usually requiring hospitalization by 67% at 150 mg and bleeding that required medical attention, but not hospitalization, by 77% at 90 mg, compared to rivaroxaban.

Moreover, at the 150 mg dose, abelacimab reduced major bleeding by 74% and at the 90 mg dose, abelacimab reduced major bleeding by 81%, compared to rivaroxaban. Both doses of abelacimab, 90 mg and 150 mg, reduced gastrointestinal bleeding by 93%, compared to rivaroxaban.

The AZALEA-TIMI 71 trial was halted prematurely on the recommendation of the independent Data Monitoring Committee in September 2023. The committee cited the reasoning as the “overwhelming reduction” in the composite endpoint of major and clinically relevant non-major bleeding events with abelacimab.²

For more insight into the results of the AZALEA study, watch the full interview with Dr. Ruff in the above video.

References

1. _{Iapoce C. Abelacimab significantly reduces bleeding in people with atrial fibrillation, study finds. HCP Live. November 12, 2023. Accessed November 15, 2023. https://www.hcplive.com/view/abelacimab-significantly-reduces-bleeding-people-atrial-fibrillation.}
2. _{Campbell P. Abelacimab demonstrates “overwhelming” efficacy vs rivaroxaban in phase 2B trial. HCP Live. September 18, 2023. Accessed November 12, 2023. https://www.hcplive.com/view/abelacimab-demonstrates-overwhelming-efficacy-vs-rivaroxaban-in-phase-2b-trial.}