Bayer: at least success with coagulation factor XIa in phase 3 of stroke trial

The new Phase III data on asundexian mark a notable turnaround for Bayer against the backdrop of a setback in 2023. At that time, the company terminated the OCEANIC-AF study prematurely. In this trial, asundexian was directly compared with the established factor Xa inhibitor apixaban in patients with atrial fibrillation. On the recommendation of the independent Data Monitoring Committee (IDMC), the study was halted after inferior efficacy compared with the control arm became apparent. However, no new safety concerns emerged for Bayer’s compound.

Even then, Bayer had emphasised that the parallel OCEANIC-STROKE study would continue as planned – a decision that is now paying off. In OCEANIC-STROKE, involving patients after non-cardioembolic ischaemic stroke or high-risk TIA, asundexian reduced the risk of recurrent ischaemic stroke by 26 per cent without increasing the risk of major bleeding. This makes it the first successfully completed Phase III study of a factor XIa inhibitor demonstrating superiority over placebo.

The indication is decisive

The differing outcomes of the two studies underline how strongly the clinical benefit of asundexian depends on the indication. While the compound was unable to prevail in direct competition with highly effective standard anticoagulants such as apixaban, rivaroxaban (Xarelto®) or edoxaban (Lixiana®) in atrial fibrillation, it now shows its potential in secondary stroke prevention in combination with antiplatelet therapy.

From a pharmacological perspective, asundexian differs clearly from established NOACs (new/non-vitamin K-dependent oral anticoagulants): it does not inhibit factor Xa, but selectively targets factor XIa. In the coagulation cascade, factor XI is converted into its active enzymatic form, factor XIa. By inhibiting factor XIa, asundexian specifically counteracts its involvement in pathological thrombus formation, while its more limited role in normal haemostasis should be less affected. This is precisely the strategic rationale behind the entire drug class: antithrombotic efficacy with a lower risk of bleeding. With its gene therapy venture AskBio Bayer is in clinical development of a therapy for another indication leading to heart failure.

Asundexian is not alone. Milvexian from Bristol Myers Squibb is another oral factor XIa inhibitor in advanced clinical development. In addition, antisense oligonucleotides and several monoclonal antibodies against factor XI/XIa are also being tested clinically. Competition is intense – but with OCEANIC-STROKE, Bayer has now been the first to demonstrate that the concept can deliver clinically in a large Phase III study.