Positive Phase 3 OCEANIC-STROKE Data Position Asundexian for Upcoming FDA Submission

According to a new announcement, Bayer’s asundexian, an investigational factor XIa inhibitor, met its primary end point in the phase 3 OCEANIC-STROKE trial, further supporting its efficacy and safety as a treatment for secondary stroke prevention. Using these notable data, the company expects to engage with regulatory authorities in preparation for a submission of asundexian in the near future.¹

OCEANIC-STROKE was a multicenter, international, randomized, placebo-controlled double-blind, event-driven phase 3 trial testing whether adding asundexian to standard anticoagulant therapy reduces the risk of recurrent stroke in patients who recently had a non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA). Overall, the trial featured more than 12,300 patients, with main study results expected to be presented at an upcoming scientific congress.

The primary end point, number of patients with composite of symptomatic ischemic stroke or covert brain infarcts detected by MRI, was met through asundexian treatment. To date, this marks the first successfully completed phase 3 trial of a factor XIa inhibitor, even in the context of secondary stroke prevention.

"We are excited by these positive topline findings which highlight the potential of Factor XIa inhibition as a new way to help protect patients from a recurrent stroke," Christian Rommel, PhD, head of research & development at Bayer’s Pharmaceuticals Division, said in a statement.¹ "This marks an important milestone in Bayer’s longstanding commitment to advancing innovation in thrombosis prevention. We extend our sincere gratitude to the investigators, patients, and colleagues whose dedication made this milestone possible."

Interest in factor XI inhibition stems from long-standing observations that those born with factor XI deficiency experience only mild bleeding yet have significantly lower rates of stroke and venous thrombosis. Prior to OCEANIC-STROKE, population studies have shown a direct correlation between higher factor XI levels and increased stroke risk, supporting factor XIa as a therapeutic target.

OCEANIC-STROKE included adults at least 18 years within 72 hours of symptom onset, who had National Institutes of Health Stroke Scale (NIHSS) scores of 15 or less. Participants must also meet at least one of three criteria: (1) a history of atherosclerotic disease (e.g., carotid stenosis, coronary disease, prior MI), not necessarily causative; (2) imaging-confirmed vascular plaque of any degree in any cervical or intracranial vessel; or (3) embolic-appearing, non-lacunar infarcts on imaging. These criteria, derived from phase 2 studies, helped select patients most likely to benefit.²

"As clinicians, we see every day how devastating a recurrent stroke can be for patients and their families. Even with currently available therapies, the risk of another stroke remains high, and each recurrence can have profound consequences," lead investigator Mike Sharma, MD, senior scientist at PHRI, and director of the Stroke Program at Hamilton Health Sciences, said in a statement.¹ "The topline results from OCEANIC-STROKE indicate that asundexian may become a new treatment option to reduce this risk – representing a potential major step forward in secondary stroke prevention."

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The interest in factor XIa inhibition in stroke prevention was accelerated after the COMPASS trial demonstrated that dual-pathway inhibition (aspirin plus low-dose rivaroxaban) reduced stroke by targeting both platelet-rich and fibrin-rich thrombi.³ This prompted the search for an anticoagulant with comparable antithrombotic benefit but a markedly lower bleeding risk, leading to the development of factor XIa inhibitors. Prior to OCEANIC-STROKE, PACIFIC-STROKE (NCT04304508) was the first phase 2 study of any antithrombotic specifically designed for stroke prevention in patients with acute stroke.

In PACIFIC-STROKE, patients within 48 hours of an acute ischemic stroke (AIS) were randomly assigned to 3 doses of asundexian (10-50 mg) or placebo, with baseline and 6-month assessments. Published in The Lancet in 2022, findings showed that asundexian did not meet its primary outcome in reducing the composite of covert brain infarction or ischemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo.⁴

At 26 weeks, the primary efficacy outcome of dose-response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischemic stroke at or before 26 weeks was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio, 0.99 [90% CI 0·79–1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1.15 [90%, 0.93–1.43]), and 90 (20%) of 447 in the asundexian 50 mg group (1.06 [90%, 0.85–1.32]; t statistic –0·68; P = 0·80).

Despite not meeting primary end point, investigators observed a signal in the 50 mg group that revealed a reduction in symptomatic stroke, particularly in patients with atherosclerosis or large-artery atherosclerosis. These findings, coupled with the favorable phase 2 safety profile, directly informed the design of OCEANIC-STROKE. Through this, investigators selected a more broader noncardioembolic population enriched for atherosclerotic disease, focusing on symptomatic events rather than MRI lesions.

NeurologyLive^® recently launched a short, multi-part series focused on asundexian, OCEANIC-STROKE, and the data that led to this point. In the clip below, Sharma discussed how findings from PACIFIC-STROKE shaped the OCEANIC-STROKE program, guiding both the choice of the 50-mg dose and the inclusion of patients with vascular disease.

REFERENCES
1. Bayer’s Asundexian Met Primary Efficacy and Safety Endpoints in Landmark Phase III OCEANIC-STROKE Study in Secondary Stroke Prevention. News release. Bayer. November 23, 2025. Accessed November 24, 2025. https://www.bayer.com/en/us/news-stories/oceanic-stroke
2. Study to Gather Information About Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following a Recent Non Cardioembolic Ischemic Stroke Which Occurs When a Blood Clot Has Formed Somewhere in the Human Body (But Not in the Heart) Travelled to the Brain. (PACIFIC-STROKE). Clinicaltrials.gov. Updated April 19, 2023. Accessed November 24, 2025. https://www.clinicaltrials.gov/study/NCT04304508
3. Kaplovitch E, Eikelboom JW, Dyal L, et al. Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease: A Subanalysis of the COMPASS Randomized Clinical Trial. JAMA Neurol. 2021;6(1):21-29. doi:10.1001/jamacardio.2020.4390
4. Shoamanesh A, Mundl H, Smith EE, et al. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Neurol. 2024;400:10357. doi:10.1016/S0140-6736(22)01588-4