Bayer has announced that the first patients have been enrolled in its Phase III OCEANIC-AF clinical trial, designed to investigate the use of the oral factor XIa (FXIa) inhibitor, asundexian, in atrial fibrillation (AF) patients at risk of stroke. The trial is part of Bayer’s wider OCEANIC clinical development program, which is also assessing the potential use of asundexian for non-cardioembolic ischemic stroke or high-risk ischaemic attack in a global Phase III trial (OCEANIC-STROKE).

The initiation of the OCEANIC-AF trial is based on encouraging data from Bayer’s Phase IIb PACIFIC-AF trial, which showed that the inhibition of FXIa by asundexian protected AF patients from thrombotic events without increasing the risk of bleeding. The increased risk of bleeding associated with current anticoagulation therapy contributes to its underuse and low adherence rates in AF patients, underscoring the need for safer treatment alternatives to prevent thrombosis. GlobalData believes that the results of the OCEANIC-AF trial will be critical as asundexian has the potential to fulfil a significant unmet need for the many AF patients who go untreated with anticoagulants due to increased risk and fear of bleeding.

Asundexian belongs to an emerging class of medicines known as factor XIa inhibitors, which are viewed as potentially safer and more effective alternatives to new oral anticoagulants (NOACs). Factor XI is a protein in the blood that is converted into its active enzyme form (factor XIa) as part of the blood coagulation cascade. Inhibiting factor XI offers an attractive strategy for stroke prevention as it reduces the formation of pathologic thrombi, while preserving the ability to form clots in response to bleeding. This contrasts with the currently used NOACs such as Eliquis (apixaban) and Xarelto (rivaroxaban), which inhibit factor Xa and consequently reduce the body’s ability to form clots. By selectively modulating coagulation, factor XIa inhibitors such as asundexian have the potential to prevent thromboembolic events without increasing the risk of bleeding like the current standard of care.

Asundexian was previously studied in the PACIFIC-AF Phase II clinical trial, which compared the safety of asundexian to the NOAC Eliquis in patients with AF at increased risk for stroke. Participants in the PACIFIC-AF trial who received apixaban had rates of severe bleeding that were three times higher than those who took asundexian, supporting the theory that inhibition of FXIa preserves a patient’s ability to clot in response to bleeding events. However, stroke reduction and overall net clinical benefit for patients with AF are two important unanswered questions that will be addressed in the OCEANIC-AF trial. This trial is designed to extend the results of the PACIFIC-AF trial, assessing safety, efficacy, and net clinical benefit associated with asundexian versus Eliquis in a larger patient population over several years.

GlobalData believes that the results of the OCEANIC-AF trial could be critical for Bayer, especially as the patents of blockbuster anticoagulants Eliquis and Xarelto will expire later this decade, paving the way for asundexian to become a potential market leader in the future.