abelacimab (MAA868) / Novartis, Anthos Therapeutics - LARVOL DELTA

Identification of Plasma Protein Biomarkers for Early-Onset Stroke through Mendelian Randomization. (PubMed, medRxiv) - "Drug-target mapping highlighted Factor XI as a leading therapeutic target, supported by existing inhibitors (e.g., abelacimab, milvexian). These findings highlight biologically plausible biomarkers and prioritize druggable targets, particularly Factor XI, for prevention of EOS and demonstrate the value of proteogenomic approaches for uncovering disease mechanisms and informing precision prevention strategies. Proteome-wide MR of 1,041 plasma proteins identified causal drivers of early-onset stroke, with strongest effects in coagulation (ABO, F7, F11) and immune-inflammatory pathways."

Biomarker • Journal • Cardiovascular • Venous Thromboembolism • EHBP1 • VAMP8

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

Effect of abelacimab vs. rivaroxaban on total bleeding events in patients with atrial fibrillation: an analysis from AZALEA–TIMI 71 (ESC 2026) - "Compared with rivaroxaban, abelacimab substantially reduces the totality of bleeding across a range of bleeding severity. These data further support the safety of FXI inhibition with abelacimab in minimizing the burden of anticoagulation-related bleeding in patients with AF."

Clinical • Atrial Fibrillation • Cardiovascular

Novartis data at ESC Congress 2026 reinforce cardiovascular leadership and showcase progress in next-generation therapies (Novartis Press Release) - "Late-breaking Phase IV VICTORION-CHALLENGE data will evaluate Leqvio (inclisiran) vs. bempedoic acid in achieving LDL-C goals; New AZALEA-TIMI 71 analyses will further characterize the bleeding profile of abelacimab in patients with atrial fibrillation, including recurrent bleeding events; Lp(a)CCELERATE, in partnership with European Atherosclerosis Society (EAS), will explore strategies to help advance guideline-recommended Lp(a) testing in clinical practice."

Clinical guideline • P2 data • P4 data • Atherosclerosis • Atrial Fibrillation

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 vitro comparison of the effects of abelacimab, dalteparin, and apixaban on catheter-induced clotting and thrombin generation. (PubMed, Res Pract Thromb Haemost) - "Abelacimab and dalteparin suppress catheter-induced clotting more effectively than apixaban. Clinical trials are needed to determine whether abelacimab prevents catheter-induced clotting in patients with cancer."

Clinical • Journal • Preclinical • Cardiovascular • Hematological Disorders • Oncology • Thrombosis • Venous Thromboembolism

LILAC-TIMI 76: Study to Evaluate the effIcacy and Safety of Abelacimab in High-risk Patients With Atrial Fibrillation Who Have Been Deemed Unsuitable for Oral Anticoagulation (clinicaltrials.gov) - P3 | N=2500 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P3 trial • Atrial Fibrillation • Cardiovascular

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

Abelacimab: Regulatory submission for atrial fibrillation in 2028 (Novartis) - Q4 & FY2025 Results

Filing • Atrial Fibrillation • Cardiovascular

Interferences of abelacimab and osocimab with routine and specific coagulation assays (ISTH 2026) - "Results of aPTT-based assays Page 2 Table or Figure Upload (2) Figure 2. Results of Thrombin Generation Assays – Calibrated Automated Thrombogram Page 3 DOI*10.1016/j.rpth.2026.105561"

Targeted Protein Degradation • PROS1

Study to evaLuate the effIcacy and Safety of abeLacimab in High-risk Patients With Atrial Fibrillation Who Have Been Deemed Unsuitable for Oral antiCoagulation (LILAC-TIMI 76) (clinicaltrials.gov) - P3 | N=2500 | Recruiting | Sponsor: Anthos Therapeutics, Inc. | N=1900 ➔ 2500 | Trial completion date: Oct 2026 ➔ Dec 2027 | Trial primary completion date: Aug 2026 ➔ Dec 2027

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

Abelacimab: Regulatory submission for atrial fibrillation in 2028 (Novartis) - Q2 2026 Results

Filing • Atrial Fibrillation • Cardiovascular

Abelacimab: Data readout from P3 LILAC-TIMI 76 trial (NCT05712200) for atrial fibrillation in 2027 (Novartis) - Q2 2026 Results

P3 data • Atrial Fibrillation • Cardiovascular

Investigating the factor XI(a) anticoagulants milvexian and abelacimab through thrombinography and fibrinography: challenges and insights (ISTH 2026) - "Further reduction of TF concentration led to thrombograms with very low amplitudes, comparable to those obtained in the absence of TF. AI usage disclosure: the authors utilized ChatGPT (OpenAI, San Francisco, CA, USA) to assist with translation and improve linguistic clarity. DOI*10.1016/j.rpth.2026.105567"

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

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

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

Emerging strategies in venous thromboembolism: a narrative review of pharmacological innovations. (PubMed, Thromb J) - "In orthopedic thromboprophylaxis, abelacimab, FXI antisense oligonucleotides, milvexian, and osocimab reduced postoperative venous thrombosis with low bleeding signals, but most data still come from prophylaxis rather than treatment trials. At present, FXI inhibition appears closest to clinical translation, whereas fibrinolysis-enhancing and thrombo-inflammatory approaches remain exploratory. Wider adoption will depend on phase 3 treatment outcomes, evidence in cancer and organ dysfunction, reversibility, cost-effectiveness, and integration into clinical guidelines."

Journal • Review • Cardiovascular • Hematological Disorders • Oncology • Respiratory Diseases • Venous Thromboembolism

Prior anticoagulation experience and bleeding risk with the factor XI inhibitor abelacimab in AZALEA-TIMI 71. (PubMed, Blood) - P2 | "The factor XI inhibitor abelacimab consistently reduced bleeding irrespective of prior OAC experience, with potentially greater absolute benefit among OAC-naïve patients. CT# NCT04755283."

Journal • Atrial Fibrillation • Cardiovascular

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

MAGNOLIA: A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE (clinicaltrials.gov) - P3 | N=417 | Completed | Sponsor: Anthos Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Genito-urinary Cancer • Oncology • Respiratory Diseases • Solid Tumor • Venous Thromboembolism

MAGNOLIA: A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE (clinicaltrials.gov) - P3 | N=417 | Terminated | Sponsor: Anthos Therapeutics, Inc. | Trial completion date: Feb 2027 ➔ Apr 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Apr 2026; Sponsor Decision

Trial completion date • Trial primary completion date • Trial termination • Cardiovascular • Genito-urinary Cancer • Oncology • Solid Tumor • Venous Thromboembolism