asundexian (BAY 2433334) / Bayer - LARVOL DELTA

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

Design, synthesis, and biological evaluation of substituted oxopyridine derivatives as selective FXIa inhibitors. (PubMed, RSC Med Chem) - "Compound 4c exhibited excellent in vitro potency, good membrane permeability and higher selectivity than asundexian. Furthermore, 4c showed an excellent pharmacokinetic property in rats after intravenous or oral administration. These results indicate that 4c can serve as a novel FXIa inhibitor that has potential clinical applications in patients."

Journal

Comparison of inhibitory effects between FXIa inhibitors and DOACs in thrombin generation assay (ISTH 2025) - "Aims This study evaluated the thrombin inhibitory effects of the FXIa inhibitors asundexian and milvexian using an intrinsic pathway thrombin generation assay (TGA) and compared these effects with those of direct oral anticoagulants (DOACs). For apixaban, the peak values at concentrations of 100–5000 ng/mL were 647.5, 570.4, 530.2, 537.4, 495.8, 403.7, and 102.8 nM, respectively; for milvexian, 497.5, 466.1, 370.8, 269.6, 169.8, 48.5 and 11.3 nM. The ranges of peak values for dabigatran, rivaroxaban, apixaban, and edoxaban at 100–1000 ng/mL were 148.1–10.0, 425.3–11.5, 547.2–156.4, and 425.4–42.5 nM, respectively."

Direct comparison of inhibitory effects by one-stage assay in factor XIa inhibitors (ISTH 2025) - "In the dilution assay, FXI activities were recovered in a dilution ratio-dependent manner for both drugs. At 5000 ng/mL, FXI activities at dilution ratios of 4, 16, and 32 were 25%, 60%, and 93% for asundexian, and 12%, 46%, and 93% for milvexian, respectively."

Reagent variability of APTT prolongation in factor XIa inhibitors of asundexian and milvexian (ISTH 2025) - "For asundexian, the ratios ranged from 1.0 to 2.5, and for milvexian, from 1.0 to 3.8, with ratios increasing proportionally with concentration. At 1000 ng/mL, APTT ranged from 3.1 to 4.1 for dabigatran, 2.0 to 2.9 for rivaroxaban, 1.3 to 1.5 for apixaban, and 1.7 to 2.2 for edoxaban."

DOAC-Stop™ reverses the anticoagulant effect of asundexian and milvexian. (PubMed, J Thromb Haemost) - "DS reverses the effect of asundexian and milvexian on the APTT and distinguishes between the APTT effects of milvexian and heparin."

Journal

Interferences Associated with the Factor XIa Inhibitors Asundexian and Milvexian in Routine and Specialised Coagulation Assays and their Removal by Activated Charcoal-Based Adsorbents. (PubMed, J Thromb Haemost) - "Emerging FXIa inhibitors interfere significantly with FXIa-dependent coagulation assays, potentially leading to misinterpretation of haemostatic function. However, charcoal-based adsorbents efficiently remove these interferences and enable routine and specialised coagulation testing in the presence of asundexian and milvexian."

Journal

Anticoagulation in Atrial Fibrillation: Is a Paradigm Shift From Xa to XIa Inhibitors on the Horizon? (PubMed, Cardiol Rev) - "The effective management of atrial fibrillation, particularly regarding the prevention of ischemic stroke and systemic embolism, has progressed with the introduction of direct oral anticoagulants, which have shown a reduction in bleeding risks when compared to warfarin. The oral factor Xa inhibitors, such as apixaban and rivaroxaban, are considered the first line for anticoagulation in cases of atrial fibrillation. Several factor XI inhibitors, including abelacimab, asundexian, osocimab, gruticibart, milvexian, and fesomersen, are currently undergoing clinical trials for similar therapeutic purposes...This review article aims to emphasize the recent trials evaluating these factor XI inhibitors with a special focus on abelacimab. Abelacimab may signify a promising advancement in anticoagulation therapy, providing potential advantages such as reduced gastrointestinal bleeding risks and the convenience of monthly dosing."

Journal • Atrial Fibrillation • Cardiovascular • Gastroenterology • Ischemic stroke

Factor XI/XIa inhibitors versus direct oral anticoagulants in atrial fibrillation with stroke risk: a GRADE-assessed meta-analysis of randomized controlled trials. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Factors XI/XIa (FXI) inhibitors, such as Abelacimab and Asundexian, offer a promising alternative. However, they are associated with a significant increase in stroke or systemic embolism risk. Further large-scale RCTs are needed to confirm these findings."

Journal • Retrospective data • Review • Atrial Fibrillation • Cardiovascular

An External Control Arm for the Oral Factor XIa Inhibitor Asundexian Phase 2 Trial in Atrial Fibrillation (PACIFIC-AF) Using Electronic Health Records. (PubMed, Cardiol Ther) - P2 | "ECAs matching the PACIFIC-AF apixaban arm could be built from EHRs with concordant event rates for key trial endpoints. The ECA approach enabled the determination of event rates for treatment duration up to 2 years, thereby informing the asundexian pivotal phase 3 trial in AF."

Journal • P2 data • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombosis

Targeting factor XI as a compromise between thrombosis and bleeding. (PubMed, Cardiol J) - "They include: a) orally administered small molecule inhibitors such as milvexian and asundexian; b) monoclonal antibodies such as abelacimab, osocimab, and xisomab, which specifically bind and inactivate FXI; c) FXI-antisense oligonucleotide (FXI-ASO), which downregulate FXI synthesis at the mRNA level and reduce plasma FXI concentrations. Their development is an important step in the history of anticoagulant therapy, striving to find a balance between preventing thromboembolism and reducing bleeding risk, ultimately improving patient outcomes. In this context, a discussion on the characteristics of FXI inhibitors, a summary on data regarding the efficacy and safety of FXI inhibitors based on preclinical and clinical studies, and an outline of future perspectives regarding therapeutic strategies of FXI inhibition in venous thrombosis are presented in this study."

Journal • Cardiovascular • Hematological Disorders • Osteoporosis • Rheumatology • Thrombocytopenia • Thrombosis