Bayer pulls atrial fibrillation study for asundexian

Bayer has decided to discontinue a phase 3 trial of its oral Factor XIa inhibitor asundexian in patients with atrial fibrillation (AF), after an interim analysis concluded the novel anticoagulant was showing “inferior efficacy” to the control arm.

The OCEANIC-AF is comparing asundexian to Pfizer and Bristol-Myers Squibb’s widely-used oral Factor Xa inhibitor Eliquis (apixaban) in AF patients at risk of a stroke, to see how well they prevent stroke and systemic blood clots.

The independent data monitoring committee overseeing the study has recommended, however, that another phase 3 trial in patients called OCEANIC-STROKE continue as planned. That study is comparing the two drugs in patients who have already suffered an acute non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack (TIA) – sometimes called a ‘mini-stroke’ – on their ability to prevent a subsequent stroke.

A placebo-controlled phase 3 trial of asundexian in older patients who aren’t eligible for directly-acting oral anticoagulants (DOACs) like Eliquis, OCEANIC-AFINA, was announced recently, but has not yet started recruiting patients, according to Bayer.

“Although the results from this analysis do not support the continuation of the OCEANIC-AF study, we will continue investigating asundexian in the OCEANIC-STROKE study and are currently re-evaluating other indications in patients in need of antithrombotic treatment,” said Dr Christian Rommel, Bayer’s R&D chief.

Bayer decided to move ahead to the phase 3 OCEANIC programme last year, even though asundexian missed efficacy targets in two mid-stage studies in ischaemic stroke and acute myocardial infarction patients when added to standard therapies.

There is a lot of interest in Factor XIa inhibitors as a class, as the drugs promise to provide similar blood-thinning properties as current anticoagulants, without raising the risk of bleeding side effects that make the treatment of diseases like AF a balancing act.

Bayer is hoping to position asundexian as a successor to Johnson & Johnson-partnered anticoagulant Factor Xa inhibitor Xarelto (rivaroxaban), its biggest-selling drug, which contributed €3.3 billion in sales in the first nine months of 2023, but is nearing the loss of patent protection.

The OCEANIC-AF setback could hand an advantage to BMS and J&J, which are developing oral Factor XIa candidate milvexian that was also advanced into phase 3 testing after a mid-stage 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) in the LIBERXIA programme, while abelacimab is in the phase 3 LILAC-TIMI 76 in patients with AF deemed unsuitable for current OAC therapy.

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