asundexian (BAY 2433334) / Bayer - LARVOL DELTA

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

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."

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

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 (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"

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

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

Factor XI and Atrial Fibrillation: A Mismatched Pairing? (PubMed, Eur Cardiol) - "The failure of the Phase III OCEANIC-AF trial comparing the FXI inhibitor asundexian to the FXa inhibitor apixaban in AF obliged the scientific community to reconsider the bleeding-free hypothesis and the pathophysiology of FXI. Here, the molecular, disease-related and pharmacological features of FXI were analysed to provide possible explanation(s) and hypotheses for this (temporary) failure of FXI targeting. Specifically, the authors describe the peculiar features of the molecule in the coagulation cascade, the possible mechanisms for the bypassing of FXI activity, the clinical evidence related to FXI congenital deficiency, levels measured in pro-thrombotic settings, the pathophysiology of different thromboembolic disorders and the pharmacodynamics of FXI blockade in Phase I and II studies."

Journal • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Orthopedics • Thrombosis

Factor XI inhibitors and atrial fibrillation: imminent breakthrough or false start? (PubMed, Eur Heart J Suppl) - "Molecules such as abelacimab, asundexian, and milvexian are under investigation for the prevention of thrombo-embolic events in patients with AF...The phase 2 AZALEA-TIMI 71 trial was prematurely terminated after demonstrating a clear reduction in the incidence of major bleeding with abelacimab compared to rivaroxaban, whereas the phase 3 OCEANIC-AF study on asundexian was stopped due to inferiority compared to apixaban. Ongoing trials, such as LILAC-TIMI 76 and LIBREXIA-AF, are crucial to confirm the efficacy and safety of this therapeutic class. While FXI inhibitors represent a potential breakthrough in the treatment of AF, further data are needed to determine their definitive role in clinical practice."

Journal • Atrial Fibrillation • Cardiovascular • Ischemic stroke

A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation. (PubMed, Clin Appl Thromb Hemost) - "In AZALEA-TIMI 71, abelacimab reduced major or clinically relevant non-major bleeding by 62%-69% versus rivaroxaban...However, OCEANIC-AF showed asundexian was inferior in stroke prevention, with a 3.8-fold higher risk of stroke or systemic embolism compared to apixaban, leading to early trial termination. Abelacimab showed a trend toward higher ischemic stroke rates abelacimab (150 mg: 1.21 vs 0.59 events/100 person-years; and 90 mg: 1.24 vs 0.59 events/100 person-years), though not statistically significant.ConclusionFactor XI/XIa inhibitors significantly reduce bleeding risk in AF patients compared to DOACs, but their thrombotic efficacy remains uncertain. While promising, further research is needed to optimize their use."

Journal • Review • Atrial Fibrillation • Cardiovascular • Ischemic stroke

Hemorrhagic Infarction Does Not Worsen Functional Outcomes in Noncardioembolic Ischemic Stroke-Secondary Analysis From PACIFIC-STROKE. (PubMed, Stroke) - "This was a secondary analysis of the PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), which enrolled patients with acute noncardioembolic ischemic stroke receiving either asundexian or placebo in addition to guideline-based antiplatelet therapy...Of note, the type of iron-sensitive sequences did not modify the results. The presence of HI did not lead to poor functional outcome on the modified Rankin Scale in patients with acute noncardioembolic ischemic stroke."

Journal • Cardiovascular • Hematological Disorders • Ischemic stroke

ORAL ANTICOAGULANTS IN ELDERLY PATIENTS WITH ATRIAL FIBRILLATION: A FREQUENTIST NETWORK META-ANALYSIS - Mrinal M. Krishna (ACC 2025) - "The risk of stroke/embolism was reduced with apixaban, rivaroxaban, and dabigatran compared with VKA. Asundexian increased the risk of stroke/embolism compared with all other drugs... In elderly patients with AF, apixaban had the highest likelihood of lower stroke/embolism, major bleeding, and ICH compared with other OACs."

Retrospective data • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Factor XI inhibitors for the prevention and treatment of venous and arterial thromboembolism. (PubMed, Nat Rev Cardiol) - "Phase II trials in orthopaedic surgery showed dose-dependent reductions in venous thromboembolism without significantly increasing bleeding compared with enoxaparin. In the first phase III trial of a small-molecule inhibitor of activated factor XI in patients with atrial fibrillation, asundexian was associated with a reduction in bleeding but also a higher risk of stroke, compared with apixaban. Factor XI inhibitors appear safe and hold promise for secondary prevention in myocardial infarction and ischaemic stroke, with ongoing phase III trials assessing their broader efficacy and safety. This Review discusses the rationale, pharmacology, evidence and future directions of factor XI inhibitors across various clinical settings."

Journal • Review • Atrial Fibrillation • Cardiovascular • Ischemic stroke • Myocardial Infarction • Orthopedics • Venous Thromboembolism

Asundexian versus Apixaban in Patients with Atrial Fibrillation. (PubMed, N Engl J Med) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

Asundexian versus Apixaban in Patients with Atrial Fibrillation. (PubMed, N Engl J Med) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

Asundexian versus Apixaban in Patients with Atrial Fibrillation. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

Asundexian or Apixaban in Patients With Atrial Fibrillation According to Prior Oral Anticoagulant Use: A Subgroup Analysis of the OCEANIC-AF Randomized Clinical Trial. (PubMed, JAMA Cardiol) - P3 | "The mechanism of these findings is unknown and deserves further research. ClinicalTrials.gov Identifier: NCT05643573."

Clinical • Journal • Atrial Fibrillation • Cardiovascular

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=12300 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Ischemic stroke

Discovery of potent, highly selective, and orally bioavailable factor XIa inhibitors for anticoagulant therapy. (PubMed, Eur J Med Chem) - "Compound 43 significantly reduced thrombosis in both FeCl3-induced mouse and rabbit arterial thrombosis models, demonstrating superior efficacy compared to asundexian. Importantly, 43 did not increase bleeding risks and exhibited a favorable safety profile in mice, suggesting its potential as a promising FXIa inhibitor for the treatment of thrombosis."

Journal • Cardiovascular • Hematological Disorders • Thrombosis