asundexian (BAY 2433334) / Bayer - LARVOL DELTA

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

Impact of asundexian on a panel of coagulation assays. (PubMed, Res Pract Thromb Haemost) - "Despite this study including a comprehensive panel of coagulation assays, asundexian may still affect other coagulation assays not assessed here. Further investigations in patients treated with asundexian are therefore warranted."

Journal • Cardiovascular • PROS1

Asundexian: A Friend or a Foe for Atrial Fibrillation? (PubMed, Clin Med Insights Cardiol) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

DOAC-Stop reverses the anticoagulant effect of asundexian and milvexian (ISTH 2025) - "Dabigatran was a positive control, and abelacimab and heparin were negative controls. DS reversed the aPTT prolongation induced by milvexian but not by heparin. Table or Figure Upload"

Comparison of the effects of abelacimab asundexian and milvexian on catheter-induced clotting (ISTH 2025) - "Abelacimab and milvexian prolonged the catheter-induced clot time by fourfold, with IC50 values of 0.04 µM and 1.12 µM, respectively, whereas asundexian had less effect. Similarly, abelacimab and milvexian attenuated catheter-induced peak thrombin with IC50 values of 13.2 nM and 112.8 nM, whereas it was 6 µM for asundexian."

Acute Coronary Syndrome • Oncology • Pulmonary Embolism • Respiratory Diseases

Effect of factor XIIa or XIa inhibitors on catheter-initiated thrombin generation: an in vitro study (ISTH 2025) - "Aims We investigated the effect of garadacimab, abelacimab, asundexian, milvexian, apixaban, dabigatran, fondaparinux and enoxaparin, compared to UFH, using a previously validated in vitro model of catheter-initiated thrombin generation (TG) in platelet-rich plasma (PRP). Adding garadacimab and abelacimab directly to collection tubes, rather than to PRP, resulted in greater efficacy, with LT increasing by 89% and 32%, respectively; in this setting, the IC50 were 25 µg/mL and 12.5 µg/mL, respectively. Table or Figure Upload"

Preclinical • Cardiovascular • Hematological Disorders • Thrombosis

An in vitro comparison of therapeutic FXIa inhibitors (ISTH 2025) - "Aims To compare the effects of milvexian, asundexian, and abelacimab on a standard activated partial thromboplastin time (aPTT) assay. Abelacimab prolonged the aPTT to 75 seconds at a concentration matching that of FXI in plasma (30nM), with no additional prolongation at higher concentrations. This value represents inhibition of 98.5% of FXI activity in normal plasma."

Preclinical • Cardiovascular • Hematological Disorders • Thrombosis

Effect of heparins, DOACs, and FXII/FXI inhibitors on catheter-initiated thrombin generation in PRP: an in vitro study. (PubMed, J Thromb Haemost) - "Heparins were by far the most effective anticoagulants in our in vitro model. Factor XIIa and XI(a) inhibitors did not adequately prevent coagulation on the studied artificial surface. DOACs and fondaparinux showed limited efficacy, aligning with clinical observations."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Thrombosis