milvexian (BMS-986177) / BMS, J&J - LARVOL DELTA

Milvexian Prevents Cardiac Ventricular Thrombosis in Patients with Myocardial Infarction: Insights from the Librexia ACS Trial (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Cardiovascular • Hematological Disorders • Myocardial Infarction • Thrombosis

LIBREXIA ACS: Milvexian after recent ACS (ESC 2026) - No abstract available

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

Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event. (PubMed, N Engl J Med) - P3 | "Among patients with a recent acute coronary syndrome event, milvexian did not decrease the risk of cardiovascular death, myocardial infarction, or ischemic stroke but did not increase the risk of intracranial or fatal bleeding, as compared with placebo. (Funded by Janssen Research and Development and Bristol Myers Squibb; LIBREXIA ACS ClinicalTrials.gov number, NCT05754957.)."

Journal • Acute Coronary Syndrome • Cardiovascular • Ischemic stroke • Myocardial Infarction

Librexia-AF, a phase 3 trial evaluating BMS’ Factor XIa inhibitor milvexian for stroke prevention in patients with atrial fibrillation, is now slated to read out in the first quarter of 2027 rather than this year. (Fierce Pharma) - "Boerner again attributed the delay to the pace of event accrual. Massacesi cited the slower pace as a potentially favorable sign that the trial could meet both its primary endpoint of noninferiority to BMS’ Eliquis and its secondary endpoint of superiority in reducing bleeding."

P3 data • Atrial Fibrillation

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

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

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 XI Inhibitors for Preventing Postoperative Venous Thromboembolism in Patients Undergoing Elective Total Knee Arthroplasty: A Network Meta-analysis of Randomized Controlled Trials. (ISTH 2026) - "The NMA compared the following Factor XI inhibitor regimens: oral milvexian (25, 50, or 200 mg once daily; 25, 50, 100, or 200 mg twice daily), intravenous abelacimab (30, 75, or 150 mg single dose), intravenous osocimab (0.3, 0.6, 1.2, or 1.8 mg/kg postoperative; 0.3 or 1.8 mg/kg preoperative), subcutaneous FXI-ASO (200 or 300 mg preoperative), and intravenous REGN7508 (250 mg) or REGN9933 (300 mg), against enoxaparin (40 mg once daily). However, the lack of a significant reduction in symptomatic events warrants confirmation in larger phase 3 trials. Table or Figure Upload (1) Figure1 Page 2 Table or Figure Upload (2) Figure 2 DOI*10.1016/j.rpth.2026.103764"

Retrospective data • Cardiovascular • Hematological Disorders • Orthopedics • Venous Thromboembolism

LIBREXIA-AF: A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation (clinicaltrials.gov) - P3 | N=20296 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: May 2027 ➔ Oct 2026 | Trial primary completion date: Mar 2027 ➔ Oct 2026

Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular

LIBREXIA-AF: A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation (clinicaltrials.gov) - P3 | N=20296 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Atrial Fibrillation • Cardiovascular

LIBREXIASTROKE: A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack (clinicaltrials.gov) - P3 | N=15000 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Cardiovascular • Ischemic stroke

LIBREXIA-AF: A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation (clinicaltrials.gov) - P3 | N=15500 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Atrial Fibrillation • Cardiovascular

LIBREXIASTROKE: A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack (clinicaltrials.gov) - P3 | N=15000 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2026 ➔ Feb 2027

Enrollment open • Trial completion date • Cardiovascular • Ischemic stroke

LIBREXIA-ACS: A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome (clinicaltrials.gov) - P3 | N=16000 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Coronary Syndrome • Cardiovascular

LIBREXIA-AF: A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation (clinicaltrials.gov) - P3 | N=15500 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Atrial Fibrillation • Cardiovascular

LIBREXIA-ACS: A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome (clinicaltrials.gov) - P3 | N=16000 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Acute Coronary Syndrome • Cardiovascular

LIBREXIA-AF: A Study of Milvexian Versus Apixaban in Participants With Atrial Fibrillation (clinicaltrials.gov) - P3 | N=20284 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | N=8505 ➔ 20284

Enrollment change • Atrial Fibrillation • Cardiovascular

LIBREXIASTROKE: A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack- LIBREXIA-STROKE (clinicaltrials.gov) - P3 | N=12532 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Ischemic stroke

LIBREXIA-ACS: A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome (clinicaltrials.gov) - P3 | N=14194 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Coronary Syndrome • Cardiovascular

LIBREXIA-ACS: A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome (clinicaltrials.gov) - P3 | N=14194 | Completed | Sponsor: Janssen Research & Development, LLC | Trial completion date: Oct 2026 ➔ Feb 2026 | Trial primary completion date: Sep 2026 ➔ Feb 2026 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Acute Coronary Syndrome • Cardiovascular