Bayer's blood thinner fails Eliquis test, sinking phase 3 trial and denting $5B sales forecast

Bayer’s plans to turn asundexian into a 5 billion euro ($5.5 billion) a year medicine have taken a hit. The factor XIa inhibitor had “inferior efficacy” to Bristol Myers Squibb and Pfizer’s Eliquis in a phase 3 trial, prompting Bayer to stop the study early while continuing to advance the asset in another indication.

Biopharma companies have identified factor XIa inhibition as a possible way to stop the formation of blood clots in veins without raising the risk of bleeding. Disentangling thrombosis from hemostasis could provide the efficacy of drugs such as Eliquis without the downsides. For Bayer, that prospect opens up a way to offset the upcoming loss of patent protection on Xarelto, a drug it sells with Johnson & Johnson.

However, asundexian has underwhelmed in the clinic. Last year, the drug candidate failed to beat placebo in a pair of midphase trials in patients recovering from heart attacks and a type of stroke. Now, the molecule has failed a phase 3 trial.

The late-stage study, OCEANIC-AF, randomized patients with atrial fibrillation at risk for stroke to receive asundexian or Eliquis. An interim look at the data showed the independent data monitoring committee that asundexian had inferior efficacy compared to the control arm, leading it to recommend stopping the trial. 

Bayer plans to analyze the data to understand why asundexian underperformed and is reevaluating the design of another phase 3 trial, OCEANIC-AFINA, in light of the setback. The German drugmaker began the phase 3 trial in patients with atrial fibrillation at high risk for stroke or systemic embolism who are ineligible for oral anticoagulation treatment earlier this month to complement OCEANIC-AF.

While the plans for OCEANIC-AFINA are in flux, Bayer is continuing to test its factor XIa inhibitor in another phase 3 trial, OCEANIC-STROKE. “Other evidence suggests the benefit of anticoagulation therapy on top of standard of care in the population of the OCEANIC-STROKE study which lacks adequate treatment options,” the company said in the Nov. 19 release.

OCEANIC-STROKE is comparing the effect of adding asundexian or placebo to the standard-of-care antiplatelets given to patients after an acute non-cardioembolic ischemic stroke or high-risk mini-stroke. Success in the study could enable Bayer to generate a return on asundexian, but the OCEANIC-AF failure raises doubts about whether the molecule can live up to expectations.

Bayer projected peak sales of more than 5 billion euros earlier this year. BMS has also tipped (PDF) its rival XIa inhibitor, the J&J-partnered milvexian, to generate sales of more than $5 billion. The two oral candidates are up against abelacimab, an injectable anti-factor XI/XIa antibody that Anthos Therapeutics picked up from Novartis with a $250 million assist from Blackstone Life Sciences.