Manesh Patel, MD after asundexian led to more strokes in the OCEANIC-AF trial.

Atrial Fibrillation

Burn the Ships? What OCEANIC-AF Means for Asundexian and Factor XI

Nearly a year after Bayer halted its OCEANIC-AF trial, the study’s ESC 2024 presentation revealed new insights into asundexian’s AFib stroke-prevention challenges and what they might mean for Factor XI inhibitors.

• Factor XI/XIa inhibitors have sparked optimism for their potential to become safer antithrombotics by avoiding anticoagulants’ bleeding risks.
• Asundexian was Bayer’s most advanced Factor XIa inhibitor, prompting estimates that it could earn the pharma giant $5.5B annually.

The phase III OCEANIC-AF trial evaluated asundexian against BMS’ popular anticoagulant apixaban (Eliquis) among 18k AFib patients with higher stroke risks. 

• However, an Independent Data Monitoring Committee recommended OCEANIC-AF’s termination after just eleven months due to asundexian’s “inferior efficacy.” 

It now appears that the committee had very good reasons to terminate OCEANIC-AF. Among the nearly 15k patients who were enrolled and treated for a median of 160 days, the asundexian patients had… 

• Over three times greater rates of stroke or systemic embolism (1.3% vs. 0.4%). 
• Over four times greater risk of ischemic stroke (csHR = 4.06).
• Far more discontinuations due to adverse events (147 vs. 118), despite similar adverse event rates.

Asundexian at least proved its bleeding advantage, as major bleeding occurred in 17 asundexian patients (0.2%), versus 53 (0.7%) taking apixaban.

Is asundexian really that much worse than apixaban for reducing stroke risks in AFib patients? Potentially, but the authors suggest that these results might have been influenced by patient selection and dosing.

• Asundexian patients who had never taken apixaban before the trial had significantly lower risks of primary events (HR = 1.42) than asundexian takers who were previously on apixaban (HR = 4.66).
• Asundexian’s 50mg daily dose also might have been too low to achieve sufficient factor XIa inhibition (estimated 94% reduction), as it might require “total suppression” for effective anticoagulation.

Other trials also give reason to be hopeful about factor XIa inhibitors. Asundexian and Anthos’ abelacimab both showed strong bleeding advantages in previous trials, BMS’ milvexian reduced stroke and bleeding risks in the phase II AXIOMATIC-SSP trial, and more late-stage trials are coming up. 

The Takeaway

Some might see OCEANIC-AF’s results as a sign that Factor XI’s “anticoagulation without bleeding risks” value proposition was too good to be true. However, there’s still plenty of evidence supporting Factor XI inhibitors’ potential, and plenty of upcoming trials that might help us understand which drugs, patients, and dosages could deliver on that potential.

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