Abelacimab for Prevention of Venous Thromboembolism
Abelacimab (MAA868) is a fully human monoclonal antibody that binds to the catalytic domain of factor XI and locks it in the zymogen (inactive precursor) conformation, thereby preventing its activation by factor XIIa or thrombin
- the intravenous infusion of abelacimab almost immediately reduces the functional factor XI level in a dose-dependent manner
- administered as a single intravenous dose injection
- when administered intravenously, abelacimab rapidly binds to factor XI and prevents its activation by locking it in the inactive precursor conformation
- by lowering the functional factor XI level, abelacimab has an effect similar to that of factor XI knockdown
Verhamme et al undertook an open-label, parallel-group trial - compared the efficacy and safety of abelacimab administered postoperatively with the efficacy and safety of enoxaparin in patients undergoing total knee arthroplasty
- randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily
- primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events
- principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery
- venous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group
- 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001)
- bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group
Authors concluded that:
- factor XI is important for the development of postoperative venous thromboembolism
- the lower incidences of thrombosis and the less extensive thrombosis observed with the higher doses of abelacimab than with enoxaparin highlight the role of factor XI in the pathogenesis of venous thrombosis after surgery
- factor XI can be activated by factor XIIa or by thrombin and is important for thrombus growth and stabilization
- abelacimab inhibits the activation of factor XI by either activator
- findings in this trial suggest that factor XI is at least as important as tissue factor in the pathogenesis of postoperative venous thromboembolism.
- factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding
Reference:
- Verhamme P et al. Abelacimab for Prevention of Venous Thromboembolism. NEJM July 19, 2021. DOI: 10.1056/NEJMoa2105872