Investigational Monoclonal Antibody Reduces Stroke Risk with Less Bleeding | AHA Scientific Sessions

In patients with atrial fibrillation, a monoclonal antibody being studied in a phase 2 trial has demonstrated a significant reduction in bleeding events. The findings from the AZALEA-TIMI 71 trial comparing the investigational abelacimab with rivaroxaban, a direct-oral anticoagulant (DOAC), were presented today at the American Heart Association Scientific Sessions meeting in Philadelphia. Principal investigator Christian T. Ruff, M.D., director of general cardiology in the Cardiovascular Division of Brigham and Women’s Hospital in Boston, presented the results.

Atrial fibrillation is an irregular and rapid heart rhythm. It can lead to blood clots in the heart and increases the risk of stroke, heart failure, and other complications. The CDC estimates that 12.1 million people in the United States will have atrial fibrillation by 2030 but 40% to 60% of people with atrial fibrillation will not be prescribed an anticoagulant to prevent strokes and blood clots, or thrombosis because anticoagulants such as rivaroxaban can lead to bleeding.

Developed by Anthos Therapeutics, abelacimab is a highly selective human monoclonal antibody that binds to Factor XI and locks into an inactive state. This prevents the formation of the activated form Factor XI. Previously, abelacimab achieved about an 80% reduction in venous thromboembolism (VTE) versus a standard-of-care comparator in a proof-of-concept efficacy study that was published in the New England Journal of Medicine.

The study presented today, AZEALEA TIMI-71, enrolled 1,287 patients with a moderate to high risk of ischemic stroke and evaluated the safety and tolerability of abelacimab. Patients were randomized to either abelacimab 150 mg or 90 mg administered monthly by subcutaneous injection or rivaroxaban daily.

Both doses of abelacimab resulted in greater than 95% inhibition of Factor XI, and the 150 mg dose achieved a 99% inhibition of Factor XI. The study met its primary endpoint of a 67% reduction in major or clinically relevant non major bleeding events compared with rivaroxaban.

Additionally, the 150 mg dose resulted in 2.7% incidence of bleeding and the 90 mg dose resulted in 1.9% incidence of bleeding, compared with 8.1% incidence of bleeding in those treated with rivaroxaban. In the patients treated with abelacimab, there was a 93% reduction in major GI bleeding and a 74% reduction in major bleeding.

A data monitoring committee in September 2023 stopped the AZEALEA trial early because of its overwhelming reduction in bleeding events. Patients in the rivaroxaban arm are eligible to transition to abelacimab in an extension study.

Martin B. Leon, M.D.

“The Factor XI inhibitors are a special new group of anticoagulants,” said Martin B. Leon, M.D., division of cardiology at Columbia University. “This study clearly demonstrated in an appropriate group of patients who were at risk for stroke with atrial fibrillation, a dramatic inhibition of Factor XI, and a dramatic reduction in bleeding complications. I hadn’t expected the magnitude of reduction of GI bleeding.”

Abelacimab 150 mg dose has been selected for testing in a phase 3 clinical trial program called LILAC-TIMI-76, which is planned for enrollment of approximately 1,900 patients at more than 400 studies. Abelacimab is also being studied in phase 3 program in cancer-associated thrombosis, comprising two trials enrolling about 2,700 patients