Abelacimab Demonstrates Safety and Efficacy for Patients With AFib of All Ages: Sid Patel, MD

Recent results from the AZAELEA-TIMI 71 trial (NCT04755283) demonstrated the safety and efficacy of abelacimab (Anthos Therapeutics) vs rivaroxaban (Xarelto) for patients with atrial fibrillation—regardless of their age. Sid Patel, MD, MPH, TIMI Study Group investigator, associate physician, Cardiovascular Division, Brigham and Women’s Hospital, and instructor of medicine at Harvard Medical School, joined The American Journal of Managed Care® (AJMC®) to discuss the implications of these findings in more detail. As abelacimab continues to successfully mitigate bleeding risks in these analyses, the researchers remain optimistic about its eventual approval and potential to shift the care landscape for patients with atrial fibrillation.

Sid Patel, MD | image credit: timi.org

These new findings were presented at the American College of Cardiology (ACC) 2025 meeting held in Chicago Illinois from March 29-31. To catch up on other exciting findings, discussions, and topics explored at this year’s ACC, visit the dedicated ACC page.

To view AJMC’s prior coverage of the AZALEA-TIMI 71 trial, please see this Q&A with Dan Bloomfield, MD, chief medical officer, Anthos Therapeutics, as well as this interview with Bloomfield and Christian Ruff, MD, MPH, director, general cardiology, Brigham and Women’s Hospital and TIMI Study Group senior investigator.

AJMC: How might these findings influence the risk-benefit assessment for prescribing anticoagulation in patients traditionally considered too high risk?

Patel: Today, several bleeding risk scores have been developed and validated to predict bleeding risk with anticoagulation in patients with atrial fibrillation. None, however, are really typically used to inform clinical decision-making around prescription of anticoagulation, given that patients who identified as “high bleeding risk” by these risk scores also have a high risk of thromboembolism.

But in the setting of factor XI inhibition, you could imagine that, if proven to be effective for stroke prevention and ultimately improved for clinical use, assessment of bleeding risk using these risk scores could help allocate these new therapies towards the patient who may derive the greatest absolute benefit given the mark reduction in bleeding that we've observed.

AJMC: How does abelacimab’s safety and tolerability compare in patients with impaired renal function or lower BMI? Do any special considerations need to be taken into account for these patients?

Patel: In our analysis, we used a bleeding risk score that integrates both of these factors: low body weight and impaired renal function, given that both of these are well-established risk factors for bleeding. It’s also important to note that rivaroxaban, which was the comparator in AZALEA-TIMI 71 to both doses of abelacimab, is typically dose reduced in those with renal disfunction. Everybody with a creatinine clearance of 50 or less actually gets the reduced dose of rivaroxaban. The reason for that is about one-third of rivaroxaban is renally excreted, whereas there's no renal elimination for abelacimab. But what we observed is that,despite this dose reduction in riveroxaban, abelacimab actually resulted in much less bleeding compared with rivaroxaban. I think these data really reaffirmed the promise of factor XI inhibition, particularly in some groups of patients who have typically posed a clinical challenge given their height and risk for both bleeding and thromboembolism.

AJMC: Forty percent of patients with atrial fibrillation do not receive optimal anticoagulation due to bleeding concerns.1,2 Can you speak to how abelacimab might address this gap in care, and what barriers might still exist?

Patel: We know from data across global registries as well as several administrative claims databases that as many as 40% of patients who, by guidelines, should be treated with anticoagulation on the basis of their thromboembolic risk remain undertreated.1,2 This is primarily due to concerns of bleeding. Because the most potent risk factors for bleeding often overlap with thromboembolism—age, frailty, or renal dysfunction—this remains a really vulnerable patient population that would stand to benefit the greatest from a safer platform of anticoagulation, such as abelacimab. This is the hypothesis that we're testing in the ongoing LILAC-TIMI 76 trial [NCT05712200], where we're evaluating the efficacy and safety of abelacimab in patients who have been deemed unsuitable for many of the currently available oral anticoagulants.

AJMC: What can you tell us about the design and goals of the ongoing phase 3 LILAC-TIMI 76 trial?

Patel: The results of LILAC-TIMI 76 will be important to demonstrate efficacy for stroke prevention in atrial fibrillation. That will be the key step for the clinical approval of abelacimab. Then, we will continue to look at several important patient populations to examine the safety of abelacimab—using the AZALEA-TIMI 71 data that we have. We anticipate presenting the results of several of those analyses at upcoming scientific meetings

References

1. Hsu JC, Maddox TM, Kennedy KF, et al. Oral anticoagulant therapy prescription in patients with atrial fibrillation across the spectrum of stroke risk: insights from the NCDR PINNACLE registry. JAMA Cardiol. 2016;1(1):55-62. doi:10.1001/jamacardio.2015.0374

2. Ko D, Lin KJ, Bessette LG, et al. Trends in use of oral anticoagulants in older adults with newly diagnosed atrial fibrillation, 2010-2020. JAMA Netw Open. 2022;5(11):e2242964. doi:10.1001/jamanetworkopen.2022.42964