asundexian (BAY 2433334) / Bayer - LARVOL DELTA

Evaluating the Safety and Efficacy of Asundexian in Cardiovascular Disease: An Updated Systematic Review and Meta-Analysis (AHA 2026) - "Abstract is embargoed at this time."

Retrospective data • Review • Cardiovascular

VB.ABPS.03. Thrombo-Inflammation and Antithrombotic Strategies: Mechanisms, Biomarkers, and Outcomes (AHA 2026) - "Themes include platelet proteostasis and signaling (Hsc70, NLRP6, HIF1α‑Syk, 12‑LOX), novel anticoagulant and antiplatelet agents and meta‑analyses (asundexian, rivaroxaban, oral PCSK9 inhibitors, MT1002), immune‑lipid links to plaque thrombogenicity (ApoB autoantibodies, PCSK9 immune remodeling), toxic lipid mitigation and supplements, cytoskeletal genetics that suppress thrombosis, and population trends in coagulopathy‑related mortality. Attendees will gain mechanistic insights and evidence to inform safer, more targeted antithrombotic care."

Biomarker • Cardiovascular • Hematological Disorders • Inflammation • Thrombosis • APOB • HIF1A • NLRP6 • SYK

Efficacy and Safety of Asundexian in Cardiovascular Diseases, Systemic Review and Meta-Analysis (AHA 2026) - "Abstract is embargoed at this time."

Retrospective data • Review • Cardiovascular

Dual antiplatelet therapy (DAPT) during the first 90 days post-randomisation in OCEANIC-STROKE: participant characteristics and interaction with asundexian (ESC 2026) - No abstract available

Late-breaking abstract • Cardiovascular

Efficacy and safety of factor XIa inhibitors for stroke prevention: a reconstructed individual patient data meta-analysis (ESC 2026) - "Traditional aggregate meta-analyses cannot adequately address heterogeneity in patient characteristics and comparator regimens.PurposeWe performed an individual patient data meta-analysis to evaluate efficacy and safety of Factor XIa inhibitors (milvexian, asundexian, abelacimab) for stroke prevention across multiple clinical settings, using reconstructed pseudo-IPD from published Kaplan-Meier curves...Major bleeding showed neutral effect (HR 1.03, 95%CI 0.67-1.57, p=0.902), though substantial heterogeneity reflected diverse comparators (placebo vs. rivaroxaban)...However, inter-trial heterogeneity driven by methodological quality differences underscores the critical need for rigorous data validation in reconstructed IPD meta-analyses. Future head-to-head trials comparing Factor XIa inhibitors directly to DOACs in adequately powered atrial fibrillation cohorts are warranted to definitively establish their clinical role."

Retrospective data • Atrial Fibrillation • Cardiovascular • Ischemic stroke

Asundexian edges out milvexian: superior stroke reduction with safer bleeding profile in factor XIa inhibition – a network meta-analysis revolutionizing secondary prevention (ESC 2026) - "Dose escalation strategies are not supported by current evidence and may increase harm. Asundexian at moderate doses (20-50mg QD) represents the optimal therapeutic approach, balancing efficacy and safety."

Retrospective data • Cardiovascular • Ischemic stroke

Efficacy and safety of novel factor XIa inhibitors in acute non-cardioembolic stroke: a network meta-analysis of randomised controlled trials (ESC 2026) - "For stroke prevention, triple therapy with aspirin (ASA), clopidogrel, and asundexian ranked as the most effective strategy (SUCRA 91.3%), followed by ASA+clopidogrel+milvexian (SUCRA 81.4%). Conclusion(s) In patients with acute non-cardioembolic stroke, the addition of asundexian to standard dual antiplatelet therapy provides an optimal net clinical benefit, significantly reducing ischaemic events without the increased haemorrhagic penalty observed with milvexian. Therefore, asundexian-based regimens may be preferred for early secondary prevention, suggesting it offers a pathway to escalate antithrombotic therapy without compromising patient safety."

Retrospective data • Atrial Fibrillation • Cardiovascular • Ischemic stroke • Thrombosis

Translational Development of Oral FXIa Inhibitors: A Systematic Review of Molecular Design, Pharmacology, and Indication-Specific Clinical Evidence. (PubMed, Pharmaceuticals (Basel)) - "In OCEANIC-AF, stroke or systemic embolism occurred in 1.3% with asundexian versus 0.4% with apixaban (HR 3.79, 95% CI 2.46-5.83), despite less major bleeding (0.2% vs. 0.7%; HR 0.32, 95% CI 0.18-0.55). Oral small-molecule FXIa inhibition is pharmacologically coherent, but clinical benefit is indication-, comparator-, and background-therapy-dependent. PD markers confirm target engagement but are not validated efficacy surrogates; hard clinical outcomes remain decisive."

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

Isolating the ischaemic and haemorrhagic effects of factor XIa inhibitors versus classical antiplatelets in acute non-cardioembolic stroke: a component network meta-analysis (ESC 2026) - "Most milvexian doses lacked significant incremental benefit, though 25mg twice daily displayed a favourable trend despite wide intervals (iHR 0.69, 95% CI 0.35-1.37). We included 79,230 patients from 24 RCTs. Regarding ischaemic protection, the addition of classical antiplatelets provided significant incremental efficacy (cilostazol iHR 0.59, 95% CI 0.42-0.83; ticagrelor iHR 0.61, 95% CI 0.51-0.73; clopidogrel iHR 0.76, 95% CI 0.66-0.87; aspirin iHR 0.72, 95% CI 0.53-0.97). Among novel FXIa inhibitors, only asundexian 50mg demonstrated significant isolated efficacy for stroke prevention (iHR 0.74, 95% CI 0.61-0.89)."

Retrospective data • Cardiovascular • Ischemic stroke • Thrombosis

Asundexian 50 mg for stroke prevention: a systematic review and meta-analysis of 14,031 patients. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Asundexian 50 mg daily significantly reduces ischemic and total stroke risk without affecting mortality in high-risk patients. These findings support factor XIa inhibition as a promising therapeutic strategy, though confirmation in additional large-scale trials is warranted."

Journal • Retrospective data • Cardiovascular • Hematological Disorders • Ischemic stroke • Thrombosis

Factor XI Inhibition for Ischemic Stroke Secondary Prevention: Pharmacology, Clinical Evidence, and Future Directions. (PubMed, J Clin Pharmacol) - "Three pharmacological classes are being studied, with distinct pharmacokinetic, pharmacodynamic, and drug-drug interaction profiles: small-molecule oral FXIa inhibitors (asundexian and milvexian), FXI antisense oligonucleotides (fesomersen), and monoclonal antibodies targeting FXI/FXIa (abelacimab and osocimab). Conversely, OCEANIC-AF showed that FXIa inhibition alone is insufficient versus apixaban in atrial fibrillation, indicating dependence upon clinical setting and suggesting the need for a precision-medicine approach integrating clinical, imaging, and biomarker-based patient stratification. This narrative review integrates pathophysiological rationale, comparative pharmacology of all FXI-targeting classes, trial evidence, and patient stratification, providing an up-to-date reference for FXI/FXIa inhibition in secondary ischemic stroke prevention."

Journal • Review • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

COMPARISON OF THE EFFECTS OF ABELACIMAB, ASUNDEXIAN, AND MILVEXIAN ON MEDICAL DEVICE-INDUCED CLOTTING AND THROMBIN GENERATION IN VITRO. (PubMed, J Thromb Haemost) - "At concentrations achieved with the dosing regimens used in the Phase 3 trials, abelacimab and milvexian had greater effects on the aPTT, catheter-induced clotting, and thrombin generation induced by catheters or MHVs than asundexian did."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Thrombosis

In noncardioembolic ischemic stroke or high-risk TIA, asundexian reduced ischemic stroke and did not increase major bleeding. (PubMed, Ann Intern Med) - "GIM/FP/GP: [Formula: see text] Neurology: [Formula: see text] Hematology: [Formula: see text]."

Journal • Cardiovascular • Hematological Disorders • Ischemic stroke

The Efficacy-Safety Paradox of Next-Generation Factor XI/XIa Inhibitors: A Bayesian Network Meta-Analysis of Phase 2 and 3 Randomized Controlled Trials (ISTH 2026) - "Methods We included phase 2 and 3 randomized controlled trials evaluating Factor XI/XIa inhibitors (asundexian, milvexian, abelacimab, osocimab) compared with standard anticoagulants (enoxaparin, direct oral anticoagulants) or placebo...Osocimab (OR 0.38, 0.05-2.61) and milvexian (OR 0.59, 0.17- 2.05) also showed favorable safety profiles compared with enoxaparin (OR 1.03) and rivaroxaban, which exhibited the highest bleeding risk (OR 8.87)...In contrast, phase 3 data in AF showed that asundexian was inferior to apixaban for stroke prevention, indicating reduced arterial efficacy despite preserved safety...These findings suggest that precision dosing, or indication-specific selection may be required to optimize clinical benefit. Table or Figure Upload (1) Forest plot showing odds ratio for Bleeding Page 2 Table or Figure Upload (2) Forest plot showing odds ratio for VTE risk DOI*10.1016/j.rpth.2026.103616"

P2 data • Retrospective data • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Venous Thromboembolism

Factor XIA Inhibition with Asundexian in Acute Non-Cardioembolic Stroke or High-Risk Transient Ischemic Attack: Primary Results of the OCEANIC-STROKE Trial (ISTH 2026) - P3 | "We randomized participants within 72 hours of acute non-cardioembolic IS (National Institute of Health Stroke Scale ≤15) or high-risk transient ischemic attack (TIA) (ABCD 2 ≥6) to asundexian 50 mg once daily or matching placebo, stratified by planned use of antiplatelets (single vs aspirin + P2Y12 inhibitor). Table or Figure Upload (1) Table 1. Baseline characteristics Page 3 DOI*10.1016/j.rpth.2026.105560"

Atherosclerosis • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Ischemic stroke • Thrombosis

The in vitro age-related effects of asundexian on coagulation in neonates, children and adults. (ISTH 2026) - "*p-Value s ignificantly different from Adults (p-value <0.05) Page 2 Table or Figure Upload (2) Figure 1: Effect of Asundexian concentration on activated factor XIa activity (%) (geometric mean ± SD) across the age-spectrum. Page 3 DOI*10.1016/j.rpth.2026.105556"

Preclinical • Cardiovascular • Ischemic stroke

Enhanced in vitro anticoagulant efficacy of factor XIa inhibitor asundexian, but not milvexian and abelacimab, in acutely ill patients with liver disease and in sepsis (ISTH 2026) - "The moderate to absent changes in anticoagulant efficacy of FXIa inhibitors in patients with liver disease contrast with more profound changes in anticoagulant potency of FXa and thrombin-directed anticoagulants, and suggest FXIa inhibitors may lead to more predictable anticoagulation use in these complex patients. DOI*10.1016/j.rpth.2026.105552"

Preclinical • Fibrosis • Hepatology • Immunology • Infectious Disease • Liver Failure • Septic Shock

Impact of (activated) factor XI inhibitors (abelacimab, asundexian, and milvexian) on coagulation assays: a pioneering multicenter study for accurate result interpretation in future patients (ISTH 2026) - "It provides recommendations for accurately interpreting results in future patients receiving these drugs. Table or Figure Upload (1) Page 2 DOI*10.1016/j.rpth.2026.105542"

Clinical • Cardiovascular • Hematological Disorders • Immunology • Inflammatory Arthritis • Thrombosis • PROS1

An Automated Lupus Anticoagulant Assay Resistant to Anticoagulant Drugs including DOACs and Oral FXI Inhibitors (ISTH 2026) - "Methods Modified CRYOcheck™ dRVVT and Hex LA formulations incorporating Act-C were prepared and compared with original formulations using LA-negative or LA-positive pooled plasma controls, contrived with UFH, LMWH (2 IU/mL), VKA (INR 3.5), DOACs (apixaban, edoxaban, rivaroxaban, dabigatran; 500 ng/mL), FXI inhibitors (asundexian, milvexian) or fondaparinux (1000 ng/mL). Table or Figure Upload (1) Table 1: Comparison of Average Clotting Times and Delta Values Between the Original and Modified Hex LA Formulations with Act-C Across Various Contrived Plasma Samples (N=2, STA-R Max 3, LA diagnostic Positivity: Delta ≥ 6 seconds). Page 2 DOI*10.1016/j.rpth.2026.104115"

Immunology • Inflammatory Arthritis

A promising enzymatic-based point-of-care assay for a rapid and accurate quantification of three new factor XI(a) inhibitors: asundexian, milvexian and abelacimab (ISTH 2026) - "Successful transfer to the POC system enables potential application with minimal sample processing, paving the way for future evaluation using clinical samples. DOI*10.1016/j.rpth.2026.104075"

Atrial Fibrillation • Cardiovascular

Proof of Concept of an Automated Anti-Factor XIa Assay for Quantification of Milvexian and Asundexian in Plasma (ISTH 2026) - "Further validation using patient samples is required to confirm its clinical applicability and support its use for routine monitoring of FXIa inhibitor therapy. Table or Figure Upload (1) Page 2 Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.104071"

Factor XIa inhibition for the prevention of thrombosis: mechanism, clinical trial signals, and indication-specific positioning. (PubMed, Curr Opin Hematol) - "FXIa contribution to thrombus formation varies by anatomic site, flow conditions, and inflammatory phenotype. The clinical data support indication-specific positioning for cancer-associated thrombosis, secondary stroke prevention, and patients at high bleeding risk, but provide weaker support for broad substitution for direct oral anticoagulants."

Journal • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Inflammation • Oncology • Thrombosis • Venous Thromboembolism • BMP7

European Medicines Agency confirms asundexian marketing authorization application for assessment in secondary prevention of ischemic stroke (Bayer Press Release) - "Validation of the application confirms the submission is complete and begins the EMA’s centralized review procedure....The application to the European Medicines Agency is based on positive data from the Phase III OCEANIC-STROKE study."

EMA filing • Ischemic stroke

A comprehensive multicenter study assessing the impact of abelacimab, asundexian and milvexian on coagulation assays. (PubMed, Blood Adv) - "Protein C anticoagulant activity was overestimated, while no impact on Protein S anticoagulant activity was observed. This study provides a comprehensive laboratory framework for interpreting clotting assays in future patients receiving FXI(a) inhibitors."

Clinical • Journal • Immunology • Inflammatory Arthritis • PROS1

Asundexian and apixaban exert differential effects on thrombin generation: insights from OCEANIC-AF. (PubMed, Eur Heart J) - No abstract available

Journal