Christian T. Ruff, MD, MPH: Abelacimab Limits Bleeding Events in AZALEA–TIMI 71 Trial

Results from the Phase 2b AZALEA-TIMI 71 trial showed abelacimab, a novel factor XI inhibitor, achieved key reductions in bleeding events versus a standard-of-care direct-oral anticoagulant (DOAC) in patients with atrial fibrillation (AF).1

Announced by Anthos Therapeutics, Inc., and published in The New England Journal of Medicine, abelacimab 150 mg lowered major or clinically relevant non-major bleeding by 62%, compared with rivaroxaban 20 mg, in a population with AF at moderate-to-high risk of stroke.2

“This is the largest and longest trial comparing a factor XI inhibition with a DOAC. I think this data is conclusive that factor XI inhibition with abelacimab in this trial is far safer than any anticoagulant strategy we have to date, and that would be a tremendous advance for a patient’s ability to be on and tolerate these medications,” Christian T. Ruff, MD, MPH, director of General Cardiology at Brigham and Women’s Hospital, and principal investigator of the AZALEA-TIMI 71 trial, told HCPLive.

Estimates have suggested nearly half of patients with AF are not prescribed anticoagulants or are undertreated, with a primary barrier of bleeding risk concerns. Approximately 60 million people worldwide are impacted by AF, expected to increase by 60% by 2050 given the aging population.3

AZALEA-TIMI 71, the longest head-to-head trial of a factor XI inhibitor, was halted early due to abelacimab’s favorable benefit-risk profile, particularly a greater-than-expected reduction in major and clinically relevant non-major bleeding. Once-monthly abelacimab 150 mg sustained a median 99% inhibition of Factor XI over 2 years.1

The incidence of major or clinically relevant non-major bleeding was 3.2 events per 100 person-years with 150 mg abelacimab, compared with 8.4 events per 100 person-years with rivaroxaban (HR, 0.38; 95% CI, 0.24–0.60; P <.001). Compared with rivaroxaban, abelacimab 150 mg also achieved a 67% reduction in major bleeding alone (HR, 0.33; 95% CI, 0.16–0.66; P = .001) and an 89% reduction in gastrointestinal (GI) bleeding (HR, 0.11; 95% CI, 0.03–0.48).

A Phase 3 trial, LILAC-TIMI 76, was launched in January 2023 to determine the safety and efficacy of abelacimab on stroke reduction in AF, compared with placebo. Anthos announced their expectation for study completion by the second half of 2026.

“We believe this is an exciting opportunity if abelacimab demonstrates its efficacy in a Phase 3 trial, it would be a tremendous advance for our most vulnerable patients,” Ruff told HCPLive. “That’s the next stage now that we’ve cemented the incredible safety profile of factor XI inhibition. Now, it’s time to demonstrate its efficacy for stroke reduction in a Phase 3 AF trial and we’re very excited that the trial is underway.”

Disclosures: Relevant disclosures for Ruff include Anthos Therapeutics, AstraZeneca, Bayer, Janssen, Novartis, and others.

References

1. Ruff CT, Patel SM, Giugliano RP, et al. Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation. N Engl J Med. 2025;392(4):361-371. doi:10.1056/NEJMoa2406674
2. Data published today in the New England Journal of Medicine demonstrates Anthos Therapeutics’ novel factor XI inhibitor, Abelacimab 150mg, reduced major or clinically relevant non-major bleeding by 62% compared to rivaroxaban (XARELTO) in patients with atrial fibrillation. Anthos Therapeutics. January 23, 2025. Accessed January 23, 2025. https://anthostherapeutics.com/press-release/anthos_2025-01-22_release/.
3. Soleimani H, Tavakoli K, Nasrollahizadeh A, et al. Estimating the burden of atrial fibrillation and atrial flutter with projection to 2050 in Iran. Sci Rep. 2024;14(1):20264. Published 2024 Aug 31. doi:10.1038/s41598-024-71296-4