Abelacimab Benefits Spectrum of Bleeding Risk with Siddharth Patel, MD, MPH

Abelacimab, a novel factor XI inhibitor, achieved reductions across the spectrum of bleeding risk, compared with rivaroxaban, in patients with atrial fibrillation (AF), with a greater absolute safety benefit in those at high bleeding risk.

Presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions, the analysis compared the safety of abelacimab to rivaroxaban using the direct oral anticoagulant (DOAC) score among 1287 patients with atrial fibrillation enrolled in the AZALEA-TIMI 71 trial.

“If you think about the risk factors for predisposition to bleeding, including advanced age, renal impairment, use of other concomitant medications, these are folks who have an indication for reducing ischemic risk, but typically post a significantly higher bleeding risk,” Siddharth Patel, MD, MPH, an associate physician in the cardiovascular division at Brigham and Women’s Hospital, told HCPLive. “We’re really encouraged by the results, the fact that even in that very high bleeding risk group, we saw the same substantial reduction in bleeding risk in those receiving abelacimab, compared with rivaroxaban.”

Results from AZALEA-TIMI 71 showed abelacimab significantly lowered the risk of major and clinically relevant non-major bleeding in patients with AF, compared with rivaroxaban. Both abelacimab doses (90 mg and 150 mg) were pooled for this analysis. Using the validated DOAC score, 8%, 33%, 37%, 16%, and 5% of patients were categorized as very low (0-3), low (4-5), moderate (6-7), high (8-9), and very high (10) bleeding risk, respectively.

Upon analysis, rates of major or clinically relevant nonmajor bleeding per 100 patient years increased stepwise based on risk scores in the rivaroxaban arm, from 5.6% in the low risk category to 21.2% in the very high risk category. In contrast, bleeding rates in the pooled abelacimab arm were 2.5% in the low-risk category versus 7.1% in the very high-risk category.

Further analysis showed the absolute risk reduction (ARR) increased from 3.1% in the low risk category to 14.1% in the very high risk category (P-trend <.001). Pending further research, regulatory approval of abelacimab could be particularly beneficial for patients with AF at high bleeding risk.

“If these therapies are confirmed to be effective for the prevention of thromboembolism in ongoing Phase 3 trials, this could really represent an opportunity to expand the armamentarium of therapies to patients who have traditionally not been anticoagulated due to history of bleeding, or even the perceived fear of bleeding,” Patel told HCPLive.

Patel reports relevant disclosures with Janssen Pharmaceuticals.

References

1. Patel SM, Giugliano RP, Morrow DA, Goodrich EL, et al. Factor XI Inhibition with Abelacimab in Atrial Fibrillation Across the Spectrum of Bleeding Risk. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

2. Anthos Therapeutics shares new data from the landmark Azalea-TIMI 71 study demonstrating the factor XI inhibitor Abelacimab significantly reduced bleeding in patients regardless of age or bleeding risk. Anthos Therapeutics. March 29, 2025. Accessed April 4, 2025. https://anthostherapeutics.com/press-release/anthos_2025-03-29_release/.