Bayer doubles down on Factor XIa with new phase 3 trial

Bayer has added another phase 3 trial into its registration programme for oral Factor XIa inhibitor asundexian, signalling growing confidence in a drug that generated mixed results in phase 2.

The new OCEANIC-AFINA study will enrol patients aged 65 and over with atrial fibrillation (AF) and at high risk of ischaemic stroke or systemic embolism, but who can’t be treated with standard oral anticoagulant therapy (OAC) because of a risk of bleeding complications.

AF is a condition characterised by an irregular and often rapid heartbeat that can lead to the formation of blood clots in the heart. These can travel through the bloodstream to plug another vessel, causing serious and life-threatening conditions such as a stroke.

OCEANIC-AFINA is focusing on a group of AF patients who have often been overlooked and excluded from clinical trials, said Bayer.

Asundexian (BAY2433334) is among an emerging crop of Factor XIa inhibitors that promise to provide the same anticoagulant properties as current OACs without raising the risk of bleeding side effects.

The drug is already being tested in two other phase 3 trials, including a study called OCEANIC-AF in up to 30,000 patients with AF and elevated risk of non-cardioembolic ischaemic strokes or transient ischaemic attacks (TIAs).

It is also being investigated as secondary prevention in the OCEANIC-STROKE study involving patients who have already suffered a stroke or high-risk TIA, as an add-on to standard antiplatelet therapy.

Last year, Bayer opted to move asundexian into phase 3 trials even though the drug missed primary efficacy endpoints in a pair of phase 2 studies in ischaemic stroke (PACIFIC-STROKE) and acute myocardial infarction (PACIFIC-AMI). The drug did meet its safety objectives, however, with no increase in bleeding rates compared to placebo.

Bayer said today that the three studies will aim to provide “robust evidence for the efficacy and safety of asundexian across a broad range of patients with AF, including those who are at high risk for both ischaemic stroke or systemic embolism and major bleeding events.”

Bayer is in a race in the Factor XI inhibitor category with other developers, including Bristol-Myers Squibb and Johnson & Johnson with milvexian – also in a phase 3 programme called LIBREXIA, despite a mid-stage stroke trial miss – as well as Anthos Therapeutics with abelacimab, an injectable Factor XI/XIa-targeting antibody that generated encouraging results in a phase 2b trial earlier this year.

Milvexian is in three late-stage studies in AF, stroke, and acute coronary syndromes (ACS), while abelacimab is in the phase 3 LILAC-TIMI 76 in patients with AF deemed unsuitable for current OAC therapy.

Anthos is also exploring another pathway with its drug, focusing on cancer patients at risk of thrombosis in its MAGNOLIA and ASTER phase 3 trials.

The lacklustre results in phase 2 studies of both asundexian and milvexian have led to speculation that the oral Factor XIa class may not meet earlier analyst expectations of multibillion-dollar sales, but their developers seem convinced their potential is worth the considerable investment in phase 3 studies. 

The results of those studies should start to emerge in 2025.