Presented at AHA 2023, the topline analysis of the phase 2 AZALEA-TIMI 71 trial showed abelacimab significantly reduced bleeding in people with Afib at risk of stroke, compared with rivaroxaban.
New topline results from the phase 2 AZALEA-TIMI 71 trial indicate abelacimab, a factor XI inhibitor, significantly reduced bleeding among people with atrial fibrillation at risk of stroke, compared to standard-of-care rivaroxaban.1
The late-breaking findings, presented at the American Heart Association (AHA) Scientific Sessions 2023 in Philadelphia, Pennsylvania, showed bleeding was reduced by ≥60% among those taking abelacimab, suggesting its safety for individuals at risk of stroke from the arrhythmia.
The AZALEA-TIMI 71 trial was halted prematurely on the recommendation of the independent Data Monitoring Committee in September 2023, owing to the “overwhelming reduction” in the composite endpoint of major and clinically relevant non-major bleeding events with abelacimab.2
“This trial confirms the promise of abelacimab to be an incredibly safe anticoagulant for stroke prevention in people with atrial fibrillation,” said study author Christian T. Ruff, MD, MPH, director of general cardiology at Brigham and Women’s Hospital, senior investigator for the TIMI Group and an associate professor of medicine at Harvard Medical School, in a statement.1
The AHA indicates individuals with atrial fibrillation experience an approximate 5-fold increased risk of stroke, compared with people without the arrhythmia. Typically, medical professionals will prescribe blood thinners or anticoagulants to reduce the risk of stroke by restricting the body’s ability to form blood clots. However, anti-clotting medications can be associated with a higher risk of life-threatening bleeding or treatment discontinuation, influencing who can safely take anticoagulants.
The investigative therapy is an injectable, monoclonal antibody categorized as a factor XI inhibitor, with the potential to prevent clots that lead to stroke and heart attack, while protecting the body’s natural ability to repair blood vessels during injury. Together, these factors could reduce the risk of bleeding among those who take abelacimab.
The AZALEA-TIMI 71 study enrolled 1,287 adults, including 44% women, across 95 global study sites, including the United States, Canada, Europe, and Asia, between March - December 2021, with a median follow-up of 1.8 years. Enrolled participants were ≥55 years old with a history of atrial fibrillation and who were taking anticoagulants. These individuals were at a moderate-to-high risk of stroke, as determined by the CHA2DS2-VASc, with a history of congestive heart failure, high blood pressure, age, type 2 diabetes, and stroke and vascular disease.
The phase 2 AZALEA-TIMI 71 trial compared bleeding occurrence in the 1,287 patients taking either 90 mg or 150 mg of abelacimab via monthly injection, compared with those taking 20 mg daily of the oral anticoagulant rivaroxaban. This is considered the longest and largest trial comparing factor XI inhibitors to the current standard-of-care use of direct-acting oral anticoagulants.
Upon analysis, the results showed abelacimab significantly reduced bleeding among people with atrial fibrillation, compared with rivaroxaban. The therapy reduced major bleeding requiring hospitalization by 67% at a dose of 150 mg and bleeding that required medical attention, but not hospitalization, by 77% at a dose of 90 mg, compared to rivaroxaban.
Moreover, at the 150 mg level, the analysis found abelacimab reduced major bleeding by 74%, compared to rivaroxaban. At the 90 mg dose, major bleeding was reduced by 81% with abelacimab. Both doses were shown to reduce gastrointestinal bleeding by 93%, compared to rivaroxaban – the therapy was well-tolerated, with a similar rate of adverse events to the standard-of-care.
Presuming the ongoing phase 3 trial data can confirm the benefit of factor XI inhibitors for stroke prevention in people with atrial fibrillation, Ruff noted it will have transformative effects on the field of cardiology.
“Our first mission in treating people with atrial fibrillation is to prevent stroke, and our ability to do this with a remarkably safe anticoagulant, such as abelacimab, would be an incredible advance,” Ruff said.1