Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, and anticoagulation therapy forms the foundation of AF treatment. Currently, there are various anticoagulant drugs used clinically, ranging from warfarin, unfractionated heparin, low molecular weight heparin, factor Xa inhibitors, to factor IIa inhibitors. However, despite their proven efficacy, the use of these anticoagulants remains limited due to concerns about increased bleeding risks, renal insufficiency, and severe comorbidities. Studies have shown that one-third of patients still do not receive or are undertreated with anticoagulant therapy, highlighting the urgent clinical need for effective treatments that do not further increase bleeding risks during the treatment period.
Based on the understanding of the coagulation process and the biological foundation of pathological thrombosis and hemostasis, Factor Ⅺa inhibitors have been identified as a potential new type of anticoagulant drug. In the process where thrombin activates prothrombin to convert it into thrombin, and thrombin then converts fibrinogen into fibrin, Factor Ⅺa plays a positive feedback role (i.e., the coagulation cascade feedback), amplifying thrombin generation, activating the coagulation cascade, and further enhancing the coagulation effect.
Asundexian is a novel oral small-molecule Factor XIa inhibitor. Clinical results to date indicate that it may offer a new option for antithrombotic therapy for more patients. Findings from the PACIFIC AF Phase II trial, an international multicenter, randomized, active-controlled, double-blind, double-dummy, parallel-group, dose-finding study, showed that in patients with atrial fibrillation, the incidence of bleeding events was lower in the Asundexian group compared to the apixaban group. This suggests that Factor XIa inhibitors may have potential in anticoagulation therapy for atrial fibrillation. Currently, the OCEANIC-AF Phase III clinical trial, which is part of the ongoing PACIFIC AF trial, aims to evaluate the efficacy and safety of Asundexian in preventing stroke or systemic embolism in atrial fibrillation patients at risk of stroke.
Recently, Bayer announced the expansion of the OCEANIC clinical research program for Asundexian (BAY2433334), launching the third Phase III OCEANIC-AFINA study. This study aims to evaluate Asundexian in atrial fibrillation patients (≥65 years old) at high risk of stroke or systemic embolism, who are considered unsuitable for oral anticoagulant therapy due to an increased risk of bleeding. OCEANIC-AFINA complements the OCEANIC-AF study, with both studies aiming to provide strong evidence for the efficacy and safety of Asundexian in a broad range of atrial fibrillation patients, including those at high risk of ischemic stroke, systemic embolism, and major bleeding.
OCEANIC-AFINA is a multicenter, international, randomized, placebo-controlled, double-blind, parallel-group, two-arm Phase III clinical trial comparing Asundexian with placebo in patients with atrial fibrillation (≥65 years) at high risk of stroke or systemic embolism who are considered unsuitable for oral anticoagulant therapy. The primary efficacy objective of the OCEANIC-AFINA study is to compare the time to first occurrence of ischemic stroke or systemic embolism in atrial fibrillation patients treated with Asundexian or placebo. The primary safety objective is the time to first occurrence of ISTH (International Society on Thrombosis and Haemostasis) major bleeding in participants receiving Asundexian or placebo. The study is expected to enroll nearly 2000 patients with atrial fibrillation.
Christian Rommel, PhD, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of Global Research and Development, stated: "Our goal is to improve patients' quality of life by reducing the fear of potentially increased bleeding, and to help doctors confidently prescribe antithrombotic treatments to protect patients. Through the OCEANIC-AFINA study, we will evaluate the efficacy of Asundexian in untreated vulnerable patient populations."
"Some patients with atrial fibrillation have a high risk of bleeding and are not suitable for existing oral anticoagulants, making clinical treatment decisions for these patients quite challenging. Moreover, such patients are often overlooked and excluded from clinical studies, so it is encouraging to see this research being conducted," said Dr. Roxana Mehran, Director of Interventional Cardiovascular Research and Clinical Trials at the Icahn School of Medicine at Mount Sinai.
It is reported that Asundexian is still in the research and development stage and has not been approved by any national or regional health authorities for any indications. It is a promising once-daily oral XIa factor inhibitor aimed at preventing thromboembolic events and reducing pathological thrombosis without interfering with hemostasis.