Factor XIa Inhibition Tied to Benefit Beyond Stroke Prevention

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Factor XIa Inhibition Tied to Benefit Beyond Stroke Prevention

Further results from the OCEANIC-STROKE trial have shown that the investigational Factor XIa inhibitor, asundexian (Bayer), not only reduces the risk of recurrent ischemic stroke but also lessens the clinical severity of those strokes when they do occur.

The trial was conducted in patients with non-cardioembolic stroke or high-risk transient ischemic attack (TIA). The main results, reported earlier this year, showed a significant reduction in ischemic stroke recurrence with asundexian versus placebo, without any increased risk of bleeding, a major achievement which has not been seen before with previous antithrombotic agents. 

Now, new analyses from the trial have been reported showing further benefits of asundexian.

“We know from the primary results of this trial that asundexian is associated with reduction in recurrent strokes. Now we have shown that recurrent strokes that do occur are less severe, and less likely to be disabling compared to the patients on placebo and that the benefits of asundexian treatment appears constant throughout the follow up period, suggesting that treatment should be continued long term,” lead investigator of the trial, Mike Sharma, MD, Population Health Research Institute, Hamilton, Canada, told Medscape Medical News. 

Article Key Points

Asundexian, a Factor XIa inhibitor, reduces recurrent ischemic stroke risk and severity without increasing bleeding risk, offering potential long-term benefits for stroke prevention. Its approval could significantly impact stroke management strategies.

Asundexian is not yet available and is currently under regulatory review in multiple countries, with hopes that it could reach the market later this year. If approved, it would likely be used in patients similar to those enrolled in the OCEANIC-STROKE trial — individuals with noncardioembolic ischemic stroke or high-risk TIA and a National Institutes of Health Stroke Scale (NIHSS) score of 15 or lower. Sharma estimates that could include about 70%-75% of stroke patients. 

“This treatment should be applicable to the majority of strokes, and most stroke patients will benefit. As we haven’t seen a bleeding hazard with this drug, that removes one of the barriers seen with other antithrombotic treatments,” he said. 

“We believe this drug will change the paradigm for stroke prevention — it will decrease the number of strokes occurring and reduce the severity of those strokes that do occur. It will be a big step forward in our goal of preventing death and disability due to stroke,” Sharma added. 

The results were presented at European Stroke Organization Conference (ESOC) 2026.

Fewer, Less Severe Strokes 

The trial enrolled 12,327 patients within 72 hours of a noncardioembolic ischemic stroke or high-risk TIA who were randomly assigned to receive either asundexian 50 mg once daily or placebo in addition to standard antiplatelet therapy.

The primary analysis showed that asundexian reduced the risk of ischemic stroke, with an absolute risk reduction of 1.9% at 1 year (hazard ratio [HR], 0.74; P < .001), without increasing the risk of major bleeding.

The latest findings showed that recurrent strokes were generally less severe among patients treated with asundexian. Among those who experienced a recurrent stroke, patients receiving asundexian were less likely to have a severe event — defined as an NIHSS score of 8 or higher — than those receiving placebo (22.9% vs 30.3%).

“We found that the strokes that do occur are milder in the asundexian group, so distribution of severity on the NIHSS is shifted towards lower scores,” Sharma said. 

Strokes that occurred in the asundexian group were also less likely to be disabling or fatal. Disabling or fatal stroke — defined as a modified Rankin Scale score of 3 or higher at 90 days — occurred in 2.1% of patients receiving asundexian compared with 3.0% of those receiving placebo (HR, 0.69; 95% CI, 0.55-0.87).

In addition, fewer patients in the asundexian group required endovascular thrombectomy (6.0% vs 7.3%), suggesting a possible reduction in large artery occlusion stroke.

“So, we have shown that patients on asundexian are less likely to have a recurrent stroke, and if they do, the stroke is not as severe, and recovery seems to be better,” Sharma noted.

Net Clinical Benefit 

In a second presentation, further data were reported showing continued separation of the event curves over time, and a net clinical benefit with asundexian.

“We calculated the hazard ratio for specific time intervals, and we see a consistent benefit at all intervals. This shows that there is no loss of efficacy with continued treatment, suggesting that it would be beneficial to continue treatment indefinitely,” said Sharma. 

“We feel that the asundexian should be thought of in the same way we think of aspirin and other medications we use to prevent stroke: they should be continued for as long as there is a risk of stroke, and to our knowledge, that doesn’t go away,” he added.

Asundexian also demonstrated significant net clinical benefit across all three prespecified composite endpoints: ischemic stroke or International Society on Thrombosis and Haemostasis (ISTH) major bleeding (7.0% vs 8.6% with placebo; P = .002); cardiovascular death, any stroke (ischemic or hemorrhagic), myocardial infarction, or ISTH major bleeding (8.5% vs 10.0%; P = .008); and all-cause mortality, disabling stroke, fatal bleeding, or symptomatic intracranial hemorrhage (3.1% vs 3.8%; P = .04).

Despite the encouraging efficacy and safety findings, questions remain about how the drug would fit into real-world clinical practice if approved.

Isabel Fragata, MD, of Centro Hospitalar Universitário de Lisboa Central in Lisbon, Portugal, who was not involved in the research, described the results as “important” but questioned how costly asundexian would be if approved, noting that the antithrombotic agents currently used for stroke prevention — such as aspirin and clopidogrel — are inexpensive and widely available 

Sharma agreed that cost will likely be a key issue if the drug reaches the market but said he hopes asundexian will ultimately be used broadly in eligible patients. He noted that the lack of an increased hemorrhage risk removes one major barrier to use and suggested that reductions in disabling and fatal stroke could help justify reimbursement for the therapy. 

This study was sponsored by Bayer. Sharma declares consulting for Bayer, Regeneron and Anthos; research funding for the current study from Bayer paid to his institution; research funding from BMS and Janssen; and serving on an endpoint review committee for AtriCure.