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Novel oral anticoagulant asundexian shows promise in phase 2 testing

The Lancet
Reuters Health - 13/04/2022 - For patients with atrial fibrillation (AF), an investigational oral inhibitor of activated coagulation factor XI (FXIa) may protect against thromboembolic events with less risk of bleeding than currently available direct oral anticoagulants (DOACs) that mainly inhibit factor X, early testing suggests.

Asundexian is being developed by Bayer, which funded the phase 2 PACIFIC-AF study, with the results reported at the American College of Cardiology 2022 Scientific Sessions and simultaneously published in The Lancet.

The trial tested asundexian 20 mg or 50 mg once daily against apixiban 5 mg twice daily in 753 patients (mean age, 73.7 years, 41% women) with AF, a CHA2DS2-VASc score of at least 2 in men or at least 3 in women, and increased bleeding risk.

Both once-daily doses of asundexian were well tolerated and led to "reliable" and "near-complete" suppression of FXIa, with significantly lower rates of bleeding compared with apixaban, the study team reports.

The primary endpoint - a composite of major or clinically relevant non-major bleeding - occurred in three patients taking 20 mg asundexian, one patient taking 50 mg asundexian, and six patients taking apixaban.

Overall, there were no cases of major bleeding and, in general, bleeding rates were lower with asundexian compared with apixaban, the team reports.

"These findings add to increasing evidence around FXIa as a therapeutic target, and specifically provide rationale for larger clinical outcome studies with asundexian," write Dr. Jonathan Piccini of Duke University, Durham, North Carolina, and colleagues.

"If effective, asundexian could have significant safety advantages in reducing bleeding over contemporary oral anticoagulants for stroke prevention. Bleeding risk remains a strong barrier to improving rates of stroke prevention in those with atrial fibrillation," they note.

"This trial was designed as a dose-finding phase 2 clinical study, and was not powered to discern or test differences in the rates of thrombotic events. Moreover, the short follow-up period of 12 weeks limits the ability to ascertain both bleeding and thrombotic events," the authors caution.

Earlier this year, the U.S. Food and Drug Administration (FDA) granted fast track designation to asundexian as a potential treatment for secondary prevention of stroke.

The study was funded by Bayer. Several authors have disclosed financial relationships with the company.

SOURCE: https://bit.ly/375zbqZ The Lancet, online April 3, 2022.

By Reuters Staff

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