Christian T. Ruff, MD, MPH is the Director of General Cardiology in the Cardiovascular Division at Brigham and Women's Hospital.

Christian T. Ruff, MD, MPH

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 

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.

“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 

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.

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.

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; 

 <.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; 

 = .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 

. “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.

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

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/.

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

Articles

The Phase 2b AZALEA-TIMI 71 trial demonstrated that abelacimab, a novel factor XI inhibitor, significantly reduced bleeding events compared to rivaroxaban in patients with atrial fibrillation (AF). Abelacimab 150 mg achieved a 62% reduction in major or clinically relevant non-major bleeding and a 67% reduction in major bleeding alone. The trial was halted early due to its favorable benefit-risk profile. A Phase 3 trial, LILAC-TIMI 76, is underway to assess abelacimab's efficacy in stroke reduction, with completion expected by 2026.

Abelacimab achieved notably lower levels of free factor XI and fewer bleeding events than standard-of-care rivaroxaban in the Phase 2b trial.

Christian T. Ruff, MD, MPH: Abelacimab Minimizes Bleeding Risk of Anticoagulants   

A new analysis of the AZALEA-TIMI 71 study showed abelacimab, a novel factor XI inhibitor, achieved consistent reductions in bleeding risk for patients on or off 

American Heart Association (AHA) Scientific Sessions 2024

, these findings on the effect of abelacimab may offer a potentially safer option for patients with 

 who experience an elevated bleeding risk with traditional anticoagulants.

“I think what a drug like abelacimab allows us to do is confidently be able to treat patients with the antithrombotic therapy that both maximizes their stroke potential from AF, but also protects them from coronary disease,” Christian T. Ruff, MD, MPH, senior investigator of the TIMI Group and director of general cardiology at Brigham and Women’s Hospital, told 

. “Even when you add an antiplatelet agent, so combination anti-thrombotic therapy, you don't see any increased risk of bleeding. That allows us to optimally manage not only our patient's AF but also their comorbidities.”

Abelacimab, a novel, investigational, highly selective, fully human monoclonal antibody, binds to factor XI to block activation and prevent the generation of the activated factor XIa form. AZALEA-TIMI 71, launched in February 2021, enrolled 1287 for a head-to-head comparison of the factor XI inhibitor to a standard-of-care anticoagulant.

Among the study population, 318 (25%) had already received antiplatelet therapy, including aspirin alone (16%), P2Y12 (7%), or dual antiplatelet therapy combining both (2%). Among the population, those treated with antiplatelet therapy had a higher rate of coronary artery disease (70% vs. 42%), previous heart attacks (36% vs. 16%), and peripheral artery disease (15% vs. 11%).

The prespecified analysis revealed a 67% reduction in bleeding for patients on antiplatelet therapy receiving abelacimab 150 mg, compared with rivaroxaban (incidence rate, 3.5% vs. 10.6%). Absolute bleeding rates were higher with the combination of rivaroxaban and antiplatelet therapy, compared with rivaroxaban alone (10.6% vs. 7.7%).

However, Ruff and colleagues noted the bleeding rates treated with abelacimab 150 mg were similar irrespective of antiplatelet therapy use (3.5% vs. 3.1%). Overall, the absolute risk difference between abelacimab 150 mg and rivaroxaban was greater in those on antiplatelet therapy, compared with those not receiving antiplatelet therapy (7.1% vs. 4.6%).

“The promise of factor XI inhibition was to deliver effective therapy to reduce thromboembolic events, but far safer,” Ruff told 

 “I think the AZALEA-TIMI 71 study cements the safety of factor XI inhibition, particularly with abelacimab, that this therapy is far safer than anything we've seen with an anticoagulant.”

Disclosures: Ruff reports no relevant disclosures.

Said SA, Patel SM, Giugliana R, Morrow DA, et al. Bleeding with the FXI Inhibitor Abelacimab compared with Rivaroxaban in Patients on Antiplatelet therapy: A Prespecified Analysis of the AZALEA-TIMI 71 Trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.

Videos

Abelacimab, a novel factor XI inhibitor, demonstrated significant reductions in bleeding risk compared to rivaroxaban in the AZALEA-TIMI 71 study, even for patients on antiplatelet therapy. This investigational monoclonal antibody offers a potentially safer anticoagulant option for atrial fibrillation patients, particularly those with elevated bleeding risks. The study showed a 67% reduction in bleeding for patients on antiplatelet therapy with abelacimab. The findings suggest that factor XI inhibition with abelacimab could provide effective thromboembolic event reduction with improved safety over traditional anticoagulants.

Christian. T. Ruff, MD, MPH describes an analysis of AZALEA-TIMI 71 demonstrating the substantial benefit of abelacimab on bleeding outcomes in patients on antiplatelet therapy.





 