Bayer AG (BAYRY) just delivered what might be the most encouraging news in the FXIa inhibitor space in quite some time. The company's Phase 3 OCEANIC-STROKE study hit both its primary efficacy and safety endpoints, showing that asundexian can actually reduce stroke risk without turning patients into bleeding risks.
Here's what happened: Asundexian at 50 mg once daily significantly reduced the risk of ischemic stroke compared to placebo when both were combined with antiplatelet therapy. The patient population was people who'd already experienced a non-cardioembolic ischemic stroke or a high-risk transient ischemic attack. To translate the medical jargon, we're talking about strokes caused by blood clots that don't originate from the heart, plus what doctors call "mini-strokes" where blood flow to the brain gets temporarily blocked.
The safety piece matters just as much as the efficacy here. There was no increase in major bleeding risk for patients on asundexian compared to placebo. That's exactly what you want to see in an anticoagulant drug, because the whole challenge is preventing clots without causing dangerous bleeding.
Why Bristol Myers Should Care
William Blair analysts see Bayer's success as potentially good news for Bristol Myers Squibb Co. (BMY), which desperately needs some positive momentum. Bristol Myers' own FXIa inhibitor, milvexian, recently hit a wall when its Phase 3 LIBREXIA-ACS trial in acute coronary syndrome patients was halted due to lack of efficacy. That's the kind of setback that makes investors nervous about an entire drug program.
But milvexian isn't dead yet. Bristol Myers has ongoing trials in stroke prevention and atrial fibrillation, and Bayer's positive data suggests the mechanism itself can work. The question, according to analyst Matt Phipps, is whether Bristol Myers is using the right doses.
The Dosing Question Everyone's Asking
Here's where things get interesting. In Bristol Myers' LIBREXIA-STROKE trial, they're using 25 mg twice daily combined with antiplatelet therapy. In the LIBREXIA-AF atrial fibrillation study, they're going with 100 mg twice daily as monotherapy. Those are very different dosing strategies, and Bristol Myers hasn't publicly disclosed how much factor XIa inhibition they're achieving at these levels.
By contrast, Bayer previously disclosed that their 50 mg once-daily dose achieves roughly 91% inhibition at trough levels. That's a pretty substantial effect on the clotting pathway.
The dosing debate isn't just academic speculation. Bayer's asundexian was previously tested against Eliquis in the OCEANIC-AF Phase 3 study for stroke prevention in atrial fibrillation patients. That trial was stopped early due to lack of efficacy. Even though asundexian achieved greater than 90% factor XIa inhibition, it was clearly inferior to Eliquis, and the level of factor XIa activity reduction looked similar whether patients had events or not.
The takeaway from that failure was pretty clear: the asundexian dose wasn't strong enough for the atrial fibrillation indication, despite hitting impressive inhibition numbers.
Can a Higher Dose Make the Difference?
Bristol Myers is betting that their 100 mg twice-daily dose in the LIBREXIA-AF study will fare better. There's some reason for optimism here. That same dose level showed compelling efficacy in the AXIOMATIC-TKR Phase 2 trial for preventing blood clots after total knee replacement surgery. Different indication, but it demonstrates the dose can deliver results.
The market certainly seems to be giving Bristol Myers the benefit of the doubt for now. BMY stock climbed 4.57% to $48.37 following the Bayer announcement, suggesting investors see potential positive read-through to the milvexian program.
Whether that optimism is justified will depend on whether Bristol Myers got the dosing right where Bayer didn't. The stroke trial results should provide some answers, and the AF data will be the real test of whether higher dosing can overcome the challenges that sank Bayer's AF program. For now, at least, the FXIa inhibitor mechanism looks viable, and that's worth something after the recent setbacks.