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Single-shot abelacimab cuts venous thromboembolism risk in knee surgery

A single abelacimab injection prevents blood clots for up to a month after surgery, reducing risk by about 80% compared with enoxaparin, without increasing the risk of bleeding, found a Canadian study, reports MedicalBrief.

McMaster University’s team, led by Jeffrey Weitz, compared abelacimab with enoxaparin as a control drug in 412 patients undergoing knee replacement surgery. Results showed that just one abelacimab injection prevents blood clots for up to a month after surgery, reducing the risk by about 80% compared with enoxaparin without increasing the risk of bleeding.

Their findings were published in The New England Journal of Medicine on 19 July, coinciding with Weitz’s presentation of the research at the International Society on Thrombosis and Hemostasis 2021 Congress.

Weitz, a haematologist, is a 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.

“Patients who undergo knee replacement routinely receive anti-clotting treatment with enoxaparin or other anticoagulant medications that require daily administration,” he said. “With a single injection of abelacimab after surgery, we found much better protection against clots in the veins in the leg compared with enoxaparin, one of the current standards of care.”

Patients enrolled in the study were closely monitored for symptoms or signs of clotting or bleeding and underwent an x-ray of the veins of the operated leg to detect any possible clot formation.

Abelacimab’s potential to treat other cardiovascular conditions has Weitz and his fellow scientists excited.

“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 Weitz.

Abelacimab is an antibody that binds to both the inactive and activated forms of factor XI, one of the clotting factors, and prevents its activation and activity, thereby halting clot formation.

The study proved that factor XI is a key driver of clot formation after surgery, Weitz said, adding that the fact that abelacimab was more effective than enoxaparin, which inhibits clotting factors downstream to factor XI, highlights the importance of factor XI in clot formation.

“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,” he said, adding that new anti-clotting medications are often tested first on patients undergoing orthopaedic surgery, such as knee replacement, because such patients are at risk for clots in the veins of their operated leg. Therefore, different doses of the drug can be evaluated to identify those that are both effective and safe compared with the standard of care such as enoxaparin.

These doses can then be carried forward into studies of patients with clots or at risk of clots, such as cancer-associated clots or stroke prevention in patients with atrial fibrillation.

The study was funded by Anthos Therapeutics, based in Cambridge, Massachusetts, which is developing abelacimab.

Study details

Abelacimab for Prevention of Venous Thromboembolism

Peter Verhamme, B. Alexander Yi, Annelise Segers, Janeen Salter, Daniel Bloomfield, Harry R. Büller, Gary E. Raskob, Jeffrey I. Weitz,
Published in New England Journal of Medicine 19 July 2021

Abstract

Background
The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.

Methods
In this open-label, parallel-group trial, we 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.
The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant non-major bleeding up to 30 days after surgery.

Results
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. The 30-mg abelacimab regimen was non-inferior 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.

Conclusions
This trial showed that factor XI is important for the development 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.

 

Full McMaster article – Abelacimab effective blood clot treatment, McMaster-led study shows (Open access)

 

New England Journal of Medicine article – Abelacimab for Prevention of Venous Thromboembolism (Open access)

 

See more from MedicalBrief archives:

 

Full-dose anticoagulants cut ICU-support and improved outcomes — 3 clinical trials

 

Concerns raised about anti-clotting drug trial

 

Thrombus formation varies according to the type of drug

 

Novel therapy acts as an antidote to blood thinner

 

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