John Mandrola, MD on why Factor XI trials have to show much more than bleeding reductions.

Pharmaceuticals

Bayer Halts Asundexia Factor XI Trial Due to Inefficacy

The Factor XI inhibitor movement hit a setback last week, after Bayer announced that it halted its OCEANIC-AF trial due to asundexian’s lack of efficacy.

• Investigative Factor XI inhibitors have sparked optimism among cardiologists for their potential to become safer antithrombotics, avoiding anticoagulants’ typical bleeding risks
• Asundexian is Bayer’s most advanced Factor XIa inhibitor, and already gained two FDA Fast Track Designations (stroke & systemic embolism prevention in Afib patients, stroke prevention after non-cardioembolic ischemic stroke)

The phase III OCEANIC-AF trial was intended to evaluate asundexian against BMS’ popular anticoagulant apixaban (Eliquis) among 18,000 Afib patients with higher stroke risks.

• The study was designed to measure asundexian’s effectiveness in preventing stroke or systemic embolism
• However, an Independent Data Monitoring Committee (IDMC) recommended OCEANIC-AF’s termination just eleven months after enrollment began due to asundexian’s “inferior efficacy” versus apixaban

Bayer didn’t provide more details on the results that prompted the IDMC’s recommendation, but as one prominent cardiologist with a large public platform noted: “To have it stopped this early must have meant there was a serious signal of lack of efficacy.”

Asundexian continued to achieve the safety benefits that Factor XI inhibitors are known for, with similar bleeding reductions as the previous PACIFIC-AF trial.

Despite this setback, the IDMC still recommended that Bayer continue with its OCEANIC-STROKE phase III trial evaluating asundexian’s ability to prevent ischemic stroke in patients who previously experienced a stroke.

• Bayer will also continue to evaluate “other indications in patients in need of antithrombotic treatment.”

There will also be more eyes on other investigative Factor XI inhibitors from Anthos Therapeutics and Janssen/Bristol Myers Squibb, noting that Anthos’s recent AZALEA-TIMI phase II trial also showed impressive bleeding reductions versus rivaroxaban, but more strokes.

The Takeaway

Some might see this as a sign that Factor XI’s “anticoagulation without bleeding risks” value proposition was too good to be true. However, it’s very possible that different Factor XI and Factor XIa inhibitors have different mechanisms, while the scientific learnings from this setback might actually lead to progress for the overall Factor XI drug class.

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The Wire

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Us2.ai’s deep learning algorithm was able to interpret echo AI left ventricular strain images with similar accuracy as conventional measurements. Read all about this milestone study and its implications for echo strain access in EHJ-Digital Health.

The Resource Wire

• The HeartFlow Story: Shifting the standard of care is a monumental undertaking, and yet physicians across the globe are embracing HeartFlow’s FFRct Analysis. Hear from the co-founder how HeartFlow got its start, and why physicians love it.  

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• Experience the future of learning: Medtronic Academy 2.0 is here! Unlock your ultimate destination for structural heart medical education with the newly redesigned Medtronic Academy 2.0. Gain access to expert-led courses, webinars, and a wealth of resources to stay ahead in cardiovascular care. Visit now!

• Streamlining Cath Lab Hemodynamic Workflows: Is your hemodynamic solution keeping your cath lab efficient? Merge Hemo is a cath lab hemodynamic monitoring solution, providing a Best in KLAS user experience, while enhancing clinical workflows, automating data collection, and streamlining inventory management.