asundexian (BAY 2433334) / Bayer - LARVOL DELTA

Factor XI Inhibitors in Atrial Fibrillation: Insights and Implications from Recent Trials. (PubMed, Adv Ther) - "For example abelacimab, an anti-FXI monoclonal antibody, demonstrated superior safety with lower bleeding rates when compared to rivaroxaban in patients with AF...However, the OCEANIC-AF trial, which studied the small molecule FXI inhibitor asundexian, was terminated early due to lack of efficacy as there was an increased rate of stroke and systematic embolism compared to the DOAC apixaban, raising new concerns about the utility of targeting FXI. However, many FXI inhibitors are currently undergoing phase 3 trials, and as such the true efficacy of the full class of FXI inhibitors remains to be elucidated. This review aims to provide a comprehensive synopsis of the landscape of FXI inhibitors in development for AF, their advantages, challenges, and known utility with a focus on how they may be applied to future anticoagulation therapy for AF."

Journal • Review • Atrial Fibrillation • Cardiovascular

Antithrombotic Therapy for Noncardioembolic Ischemic Stroke: Current Evidence and Future Directions. (PubMed, Stroke) - "The recently positive OCEANIC-STROKE trial testing dual-pathway inhibition with the factor XIa inhibitor asundexian in combination with antiplatelet therapy represents a major advance in antithrombotic therapy for noncardioembolic stroke. This review summarizes the current state of the evidence for antithrombotic therapy in secondary stroke prevention after noncardioembolic stroke and discusses completed and ongoing trials of novel factor XI/XIa inhibitors for stroke prevention."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Ischemic stroke • Thrombosis

21174: A study to learn about the amount of asundexian in the blood and the effect of food on its levels when healthy participants take it as adult or pediatric formulation (clinicaltrialsregister.eu) - P1 | N=18 | Not yet recruiting | Sponsor: Bayer AG

New P1 trial • Cardiovascular • Pediatrics

Direct Oral Anti-Xa Anticoagulants and the Future of Factor XI/FXIa Inhibition: A New Paradigm in Thrombosis Prevention. (PubMed, Pharmacy (Basel)) - "This biological paradigm has catalyzed the development of novel FXI/FXIa inhibitors, including small-molecule agents (asundexian, milvexian) and biological therapies (abelacimab). Clinical trials such as AXIOMATIC-TKR, PACIFIC-AF, and OCEANIC-AF, and ongoing programmes including ASTER and MAGNOLIA suggest that FXI inhibition may preserve antithrombotic efficacy while substantially reducing bleeding risk. This review summarizes the current landscape of oral FXa inhibitors, outlines the biological rationale for FXI/FXIa inhibition, and discusses the evolving clinical evidence supporting what may represent the next major advance in anticoagulant therapy."

Journal • Review • Cardiovascular • Gastroenterology • Genito-urinary Cancer • Geriatric Disorders • Hematological Disorders • Nephrology • Oncology • Renal Disease • Thrombosis • Venous Thromboembolism

Factor XI inhibition in atrial fibrillation: where do we stand? (PubMed, G Ital Cardiol (Rome)) - "The phase II AZALEA-TIMI 71 trial was terminated early after showing a significant reduction in the incidence of major bleeding with abelacimab compared with rivaroxaban. In contrast, the phase III OCEANIC-AF trial of asundexian was halted due to inferiority versus apixaban...While FXI inhibitors represent a potential innovation in the treatment of AF, additional evidence is required to clearly and definitively define their role in clinical practice. This review aims to examine the pathophysiological rationale underlying the use of FXI inhibitors, to describe the different molecular subclasses currently under development, and to summarize the results of both completed and ongoing clinical trials of this novel therapeutic class, with the goal of outlining future perspectives for thromboembolic prevention in patients with AF."

Journal • Review • Acute Coronary Syndrome • Atrial Fibrillation • Cardiovascular • Ischemic stroke

ESO annual stroke evidence update 2025. (PubMed, Eur Stroke J) - "In 2025, trial evidence supported no routine role for EVT in MeVO, reinforced tenecteplase as bridging thrombolysis in eligible LVO patients undergoing EVT and strengthened the signal for early intensive blood pressure lowering in acute ICH. Priority research questions include identifying subgroups that may benefit from EVT in MeVO, defining the role of adjunct intra-arterial thrombolysis after successful EVT and clarifying which imaging-based selection pathways are most feasible and effective across different stroke systems."

Journal • Review • Alzheimer's Disease • Atrial Fibrillation • Cardiovascular • Cognitive Disorders • Ischemic stroke

Dose-Response Efficacy and Safety of Factor XI/XIa Inhibitors in Atrial Fibrillation; a Systematic Review and Meta-Analysis With Subgroup Exploration and Trial Sequential Validation. (PubMed, Clin Cardiol) - "Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality."

Clinical • Journal • Retrospective data • Review • Atrial Fibrillation • Cardiovascular

Bayer’s asundexian demonstrated a substantial, 26 percent reduction in stroke after a non-cardioembolic ischemic stroke or high-risk transient ischemic attack with no increase in ISTH major bleeding versus placebo (Bayer Press Release) - "Asundexian significantly reduced ischemic stroke by 26 percent (csHR 0.74; 95% CI 0.65–0.84; p<.0001), in patients after a non-cardioembolic ischemic stroke or high-risk transient ischemic attack, with no increase in the risk of ISTH (International Society on Thrombosis and Hemostasis) major bleeding...secondary endpoints showed asundexian reduced the risk of a stroke of any kind (ischemic and hemorrhagic) by 26 percent (6.6% vs. 8.8%; csHR 0.74; 95% CI, 0.65–0.84; p<.0001) compared to placebo."

P3 data • Ischemic stroke

Qualifying Ischemic Stroke Subtypes and Response to Asundexian: Prespecified Secondary Analysis of the OCEANIC-STROKE Trial (ISC 2026) - P3 | "The event-driven trial is expected to be completed in late 2025, with prespecified secondary results by qualifying ischemic stroke subtype to be presented at ISC 2026.Conclusions : OCEANIC-STROKE will be the first completed phase 3 trial evaluating FXIa inhibitor asundexian for secondary stroke prevention. These prespecified analyses will clarify whether ischemic stroke subtype modifies the efficacy or safety of asundexian, supporting personalized antithrombotic strategies in patients with non-cardioembolic ischemic stroke."

Late-breaking abstract • Atherosclerosis • Cardiovascular • Ischemic stroke

Characteristics and Outcomes of the Real-World Cohort of Patients with Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack Compatible With the OCEANIC-STROKE Clinical Trial Population in Japan (ISC 2026) - P3 | "Introduction: The Phase III OCEANIC-STROKE trial (NCT05686070) investigates whether the activated Factor XI inhibitor asundexian combined with antiplatelet therapy (APT) reduces the risk of recurrent IS in patients with non-cardioembolic IS (NCIS) or high-risk TIA compared with APT alone... In real-world settings, patients compatible with the enrolled OCEANIC-STROKE trial population had a high risk of IS recurrence following hospital discharge in Japan. Further improvements in secondary stroke prevention strategies are merited."

Clinical • Real-world • Real-world evidence • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke

Trialist: Factor XIa Inhibition with Asundexian in Acute Non-Cardioembolic Stroke or High-Risk Transient Ischemic Attack: Primary Results of the OCEANIC-STROKE Trial (ISC 2026) - No abstract available

Late-breaking abstract • Cardiovascular • Ischemic stroke

Factor XIa Inhibition with Asundexian in Acute Non-Cardioembolic Stroke or High-Risk Transient Ischemic Attack: Primary Results of the OCEANIC-STROKE Trial (ISC 2026) - P3 | "Main results will be available for ISC 2026.Conclusions : OCEANIC-STROKE will be the first completed phase 3 trial investigating the FXIa inhibitor asundexian for the prevention of ischemic stroke in patients with non-cardioembolic stroke or high-risk TIA. The trial includes a large, representative population and the results should be widely applicable."

Late-breaking abstract • Atherosclerosis • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke

Simplifying the next-generation of anticoagulants: Elexians - Why a unified nomenclature for FXI/Xia inhibitors is needed. (PubMed, Thromb Res) - No abstract available

Journal

Development of selective NBD-based fluorescent probes for in vitro detection of factor XIa and Thrombus imaging. (PubMed, Bioorg Chem) - "FNC2 visualized FXIa in human plasma clots with 2.7-fold higher signal than free NBD, suppressed dose-dependently by asundexian. This structure-guided approach yields selective probes for FXIa detection and thrombus imaging."

Journal • Preclinical • Thrombosis

Rationale, design and baseline characteristics of participants in the OCEANIC-STROKE trial of FXIa inhibition for secondary stroke prevention. (PubMed, Eur Stroke J) - P3 | "OCEANIC-STROKE will be the first completed trial of FXIa inhibition for prevention of stroke after non-cardioembolic stroke or TIA."

Clinical • Journal • Atherosclerosis • Cardiovascular • Hematological Disorders • Hemophilia • Ischemic stroke

Individualized antithrombotic therapy in acute coronary syndrome: The role of thrombin pathway inhibition and aspirin. (PubMed, Kardiol Pol) - "In this scenario, potential oral agents include FXa (rivaroxaban, apixaban, edoxaban), FXIa (asundexian and milvexian) and FXIIa inhibitors. Understanding the relative contributions of platelet and coagulation pathways to clot formation in an individual patient is likely critical to achieve a balance between anti-ischemic effects and bleeding risk. In this line, we discuss the importance of objectively measuring thrombogenicity and its potential role in personalizing DPI strategies in patients with ACS."

Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular

Design, synthesis and biological evaluation of novel FXIa inhibitors featuring five-membered heterocycles as P2' fragments. (PubMed, Eur J Med Chem) - "In this study, a series of novel small-molecule FXIa inhibitors were designed based on the scaffold of Asundexian through a bioisosteric replacement strategy...Furthermore, acute toxicity evaluation demonstrated its good safety and tolerability. Overall, FE12 exhibits an excellent balance of potency, selectivity and safety, representing a promising lead compound for the development of small-molecule FXIa inhibitors."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Coagulation factor XI and coronary artery disease: is there room for factor XI inhibitors? (PubMed, Pol Arch Intern Med) - "Among FXI inhibitors, asundexian was evaluated in patients following acute MI in a phase 2 randomized PACIFIC AMI trial, without clear benefits from this intervention, while the phase 3 LIBREXIA ACS study aimed to assess milvexian on top of dual antiplatelet therapy in the prevention of secondary ischemic events in high-risk MI survivors was discontinued after interim analysis on basis of futility. The current review summarizes the latest preclinical and clinical studies on the role of FXI in atherogenesis and its thromboembolic manifestations. Moreover, it discusses potential therapeutic options offered by FXI inhibitors."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Ischemic stroke • Myocardial Infarction • Thrombosis

Asundexian: a systematic review of safety, efficacy, and pharmacological insights in thrombosis. (PubMed, Thromb J) - "Asundexian shows promise in reducing bleeding but lacks efficacy in high-risk settings like atrial fibrillation. Ongoing trials are needed to define its role in specific thrombotic conditions."

Journal • Review • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombosis • Women's Health

OCEANIC-STROKE: A Study to Test Asundexian for Preventing a Stroke Caused by a Clot in Participants After an Acute Ischemic Stroke or After a High-risk Transient Ischemic Attack, a So-called Mini Stroke (clinicaltrials.gov) - P3 | N=12327 | Completed | Sponsor: Bayer | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Ischemic stroke

Population Pharmacokinetics of Asundexian in People at Risk for Thromboembolic/Cardiovascular Events. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P3 | "Similarly, no significant differences in PK were noted among participants with atrial fibrillation, ischemic stroke, or acute myocardial infarction. No clinically relevant covariates were identified that would warrant dose adjustments in various special populations of interest, including those defined by body weight, age, sex, and renal function, for the prevention of secondary ischemic strokes."

Journal • PK/PD data • Atrial Fibrillation • Cardiovascular • Ischemic stroke • Myocardial Infarction • CYP3A4

Network Meta-Analysis of Dose-Dependent Effects of Factor XIa Inhibitors vs Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation (AHA 2025) - "Current evidence does not support XIa inhibitors superiority over DOACs for AF. The increased risk of ischemic stroke at higher doses, particularly with Asundexian 50 mg, is clinically unacceptable when compared to established DOACs. While some doses show favorable safety rankings, these do not translate into clear clinical benefit."

Retrospective data • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke

FACTOR XIA (FXIA) INHIBITION WITH ASUNDEXIAN AFTER ACUTE NON-CARDIOEMBOLIC STROKE OR HIGH RISK TRANSIENT ISCHEMIC ATTACK (TIA): METHODS AND BASELINE DATA FOR THE OCEANIC-STROKE TRIAL (WSC 2025) - P3 | "Dual antiplatelets were planned in 63% as standard of care initial treatment. Trial completion is anticipated in October 2025.ConclusionsOCEANIC-STROKE will be the first completed trial of FXIa inhibition for prevention of stroke after non-cardioembolic stroke or TIA."

Late-breaking abstract • Atherosclerosis • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke

Factor XI and Cancer: Physiopathological Linkage and Clinical Perspectives. (PubMed, J Clin Med) - "Several molecules, such as asundexian and abelacimab, are in clinical trials for the prevention and treatment of venous thromboembolic events, catheter-related thrombosis, and arterial thromboembolic events in cancer patients. The use of FXI inhibitors emerges as a promising therapeutic strategy, offering potentially positive effects in the prevention and treatment of thromboembolic complications without significantly increasing the risk of bleeding, a limitation of conventional anticoagulants. The preliminary evidence is that further clinical trials are required and that the available data is not enough to make firm clinical recommendations."

Journal • Review • Cardiovascular • Hematological Disorders • Oncology • Thrombosis

Evaluating the Safety and Efficacy of Asundexian in Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Clin Appl Thromb Hemost) - "These findings suggest that Asundexian, at the studied doses, does not provide significant clinical advantages in mortality or thromboembolic outcomes but may have a favorable bleeding profile. Further research is needed to define its potential role in specific high-risk populations."

Journal • Retrospective data • Review • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Ischemic stroke • Myocardial Infarction • Thrombosis