Exploring the therapeutic utility of the factor XIa inhibitor asundexian

Factor XIa inhibitors are a promising novel class of anticoagulants that attenuate pathological thrombosis with minimal interference with hemostasis. These effects contrast with those of conventional anticoagulants, which may exhibit adverse events of untoward bleeding precluding treatment in some p...

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Bibliographic Details
Published in:American journal of health-system pharmacy 2024-12, Vol.81 (24), p.1222-1229
Main Authors: Edwards, Jocelyn, Corey, Jack, Coons, James C
Format: Article
Language:English
Subjects:
Anticoagulants - administration & dosage
Anticoagulants - adverse effects
Anticoagulants - therapeutic use
Atrial Fibrillation - drug therapy
Benzamides
Factor Xa
Factor XIa - antagonists & inhibitors
Hemorrhage - chemically induced
Humans
Hydrocarbons, Fluorinated
Recombinant Proteins
Stroke - prevention & control
Thrombosis - drug therapy
Thrombosis - prevention & control
Triazoles
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Summary:Factor XIa inhibitors are a promising novel class of anticoagulants that attenuate pathological thrombosis with minimal interference with hemostasis. These effects contrast with those of conventional anticoagulants, which may exhibit adverse events of untoward bleeding precluding treatment in some patients. A variety of investigational pharmacological modalities have been developed and studied to target factor XIa. Asundexian is a small molecule inhibitor of factor XIa that has been evaluated in several clinical studies. It has been studied as an oral, once-daily medication and found to inhibit approximately 90% of factor XIa activity at doses of 20 to 50 mg. Phase 2 trials have demonstrated the potential for improved safety compared to standard of care in certain treatment settings, such as in atrial fibrillation. For other indications, such as noncardioembolic stroke and acute myocardial infarction, asundexian has been used in addition to background antiplatelet therapy. In these instances, asundexian did not show a difference in the incidence of bleeding events compared to placebo. Phase 3 trials have recently been launched; however, the OCEANIC-AF trial was prematurely discontinued due to inefficacy of asundexian vs apixaban for stroke prevention in atrial fibrillation. Another phase 3 trial, OCEANIC-AFINA, is planned to compare asundexian to placebo in patients with atrial fibrillation at high risk for stroke who are deemed ineligible for anticoagulation.
ISSN:1079-2082
1535-2900
1535-2900
DOI:10.1093/ajhp/zxae182