Asundexian Phase 3 AF Study Halted for Lack of Efficacy

The phase 3 OCEANIC-AF trial of the investigational oral factor XI inhibitor asundexian (Bayer) has been stopped early owing to inferior efficacy of the drug in comparison with apixaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF).

This decision is based on the recommendation of the study’s independent data monitoring committee in light of ongoing surveillance that showed that asundexian was inferior in efficacy in comparison with apixaban, Bayer announced.

The company says it will further analyze the data to understand the outcome and will publish the data. Appropriate measures will be taken to close the OCEANIC-AF study. Patients will be contacted by their treating physicians/investigators to discuss next steps.

Another phase 3 trial of the use of asundexian after acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, OCEANIC STROKE, is continuing as planned. In that trial, asundexian is being compared to placebo on top of standard of care (antiplatelet therapy).

Other evidence suggests benefit of anticoagulation therapy on top of standard of care in the population enrolled in the OCEANIC-STROKE study, for which adequate treatment options are lacking, the company says.

“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 Christian Rommel, PhD, global head of research and development at Bayer, in a company press release.

A third phase 3 trial, OCEANIC-AFINA, was planned. In that trial, asundexian was to be compared with placebo for patients with AF who are at high risk for stroke or systemic embolism and who are deemed ineligible for oral anticoagulant treatment because of concerns regarding bleeding. This trial has not yet started recruiting patients; Bayer says it will now reevaluate the study design in light of the OCEANIC-AF decision.

The stopping of the OCEANIC-AF trial for lack of efficacy will be seen as a massive blow to the whole factor XI inhibitor field. These agents were being heralded as possible anticoagulation candidates that, unlike previous therapies, are not linked to a high risk of bleeding.

Phase 2 studies have shown far less bleeding with factor XI inhibitors than with NOAC agents such as apixaban and rivaroxaban, and it was hoped that these agents would provide anticoagulation more safely.

The OCEANIC-AF study is one of the first major efficacy trials of a factor XI inhibitor. Similar agents are being studied in phase 3 efficacy trials in patients with AF, including abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and another small molecule, milvexian (BMS/Janssen).