A single dose of abelacimab reduces VTE after knee replacement surgery

According to the results of a randomized study, a single IV dose of the anti-factor XI monoclonal antibody abelacimab was shown to be superior to daily enoxaparin for the prevention of venous thromboembolism after total knee replacement surgery.

The results – presented at the congress of the International Society on Thrombosis and Hemostasis and published in The New England Journal of Medicine – has shown that abelacimab (Anthos Therapeutics) reduces the risk of blood clots by about 80% without increasing the risk of bleeding.

The results illustrate the importance of factor XI in the development of postoperative VTE, the researchers concluded.

Jeffrey Weitz

“We expect factor XI to be a safer target for newer anticoagulants than the targets of currently available anticoagulants, as patients with congenital factor XI deficiency have a reduced risk of clots, but rarely experience spontaneous bleeding. ” Jeffrey Weitz, MD, FRCP, FACP, FCCP, professor of medicine and professor of biochemistry and biomedical sciences at the Michael G. DeGroote School of Medicine at McMaster University and executive director of the Institute for Thrombosis and Atherosclerosis Research, said in a press release .

Patients who have knee replacement surgery are usually on anticoagulant therapy with enoxaparin or other anticoagulants that require daily administration.

The role of factor XI in the pathogenesis of postoperative VTE has not been established.

Abelacimab – a fully human monoclonal antibody – binds to both activated and inactive forms of factor XI, preventing its activation and activity and, thus, stopping the formation of clots.

Weitz and his colleagues conducted an open-label parallel group trial that included patients undergoing total knee replacement surgery.

Researchers randomized 299 patients to receive abelacimab regimens given postoperatively in single IV doses of 30 mg (n = 102), 75 mg (n = 99), or 150 mg (n = 98). The remaining 101 patients received 40 mg of enoxaparin administered as a subcutaneous dose once daily.

The incidence of VTE detected by mandatory venography of the leg or objective confirmation of symptomatic events was used as the primary efficacy endpoint.

A composite of clinically relevant major and non-major bleeding up to 30 days after surgery was used as the primary safety outcome.

Researchers reported lower VTE levels in the three abelacimab groups – 13% for the 30 mg dose, 5% for the 75 mg group, and 4% for the 150 mg dose – than the enoxaparin group. (22%).

The 30 mg abelacimab regimen appeared to be non-inferior to the enoxaparin regimen, while the 75 mg and 150 mg abelacimab regimens significantly reduced VTE compared to enoxaparin (P <0.001 for both).

The researchers reported bleeding in 2% of patients who received the abelacimab dose of 30 mg and in 2% of patients at the 75 mg dose. No patient who received the 150 mg dose of abelacimab or enoxaparin experienced any bleeding.

“This success of abelacimab in this study forms the basis of its use for the prevention of stroke. [among] patients with atrial fibrillation, and for the treatment of deep vein thrombosis and pulmonary embolism … [among] cancer patients, ”Weitz said.