Exploring the therapeutic utility of the factor XIa inhibitor asundexian.

Abstract

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. 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 50mg. 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.