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A 412-patient trial comparing 3 dosing regimens of abelacimab versus enoxaparin, results indicate all 3 regimens of abelacimab demonstrated noninferiority against enoxaparin and 2 of the 3 demonstrated superiority against the current standard of care.
Results of an open-label, parallel-group trial suggest use of abelacimab, a novel, fully human, Factor XI and XIa antibody, was associated with a reduction in risk of blood clots following surgery without increasing the risk of bleeding compared to current standard of care.
A comparison of abelacimab to enoxaparin in a cohort of 412 patients undergoing orthopedic surgery, results of the trial not only demonstrate the ability of abelacimab to aid in prevention of blood clots but also outline the role of factor XI in clot formation following surgery.
"This success of abelacimab in this study provides the foundation for its use for prevention of stroke in patients with atrial fibrillation and for treatment of deep-vein thrombosis and pulmonary embolism, clots in the veins of the leg and clots in the lung, in patients with cancer," said Jeffrey Weitz, MD, senior investigator of the trial who also serves as the professor of medicine and of biochemistry and biomedical sciences at McMaster's Michael G. DeGroote School of Medicine and executive director of the Thrombosis and Atherosclerosis Research Institute, in a statement.
Named ANT-005 and funded by Anthos Therapeutics, the multicenter, randomized, open-label trial was designed to compare intravenous abelacimab in 30 mg, 75, mg, or 150 mg doses against enoxaparin 40 mg. Conducted at 16 centers in 5 countries, the trial enrolled a population of 412 patients undergoing total knee arthroplasty. The trial’s primary efficacy outcome of interest was the incidence of venous thromboembolism and the primary safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery.
For the primary efficacy outcome, which was assessed via a mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events, results indicated venous thromboembolism occurred among 13 of 102 (13%) patients in the 30 mg abelacimab group, 5 of 99 (5%) patients in the 75 mg group, and 4 of 98 (4%) patients in the 150 mg group, and 22 of 101 (22%) patients in the enoxaparin group.
Results of the investigators’ analyses indicated the 30 mg dose of abelacimab was noninferior to enoxaparin and the 75 mg and 150 mg doses of abelacimab were considered superior to enoxaparin (P <.001). Additionally, the difference in risk seen with abelacimab compared to enoxaparin was -9.2 percentage point for 30 mg abelacimab (95% CI, -19.4 to 1.1; P=.08 for superiority), -16.8 percentage points for 75 mg abelacimab (95% CI, -26.0 to -7.6; P <.001 for superiority), and -17.8 percentage points with 150 mg abelacimab (95% CI, -26.7 to -8.8; P <.001 for superiority).
In safety analyses, bleeding events were observed in 2% of patients receiving 30 mg abelacimab, 2% receiving 75 mg abelacimab, and 0 patients receiving 150 mg abelacimab. No bleeding events were observed among patients in the enoxaparin group.
In the aforementioned statement, Weitz outlined the potential impact of using factor XI as a target for anticoagulation strategies.
"We expect factor XI to be a safer target for new anticoagulants than the targets of currently available anticoagulants because patients with congenital factor XI deficiency are at reduced risk for clots but rarely have spontaneous bleeding," Weitz added.
This study, “Abelacimab for Prevention of Venous Thromboembolism,” was published in the New England Journal of Medicine and presented at the International Society on Thrombosis and Hemostasis 2021 Congress.