abelacimab (MAA868) / Novartis - LARVOL DELTA

Abelacimab: Regulatory submission for atrial fibrillation in 2027 (Novartis) - Q3 2025 Results

Filing • Atrial Fibrillation • Cardiovascular

Abelacimab for Acute Pulmonary Embolism: Translating Dual FXI/XIa Inhibition from Mechanism to Clinical Prospects. (PubMed, Clin Appl Thromb Hemost) - "For these patients, anticoagulation is the mainstay, but the use of conventional agents (warfarin, DOACs, heparins) is severely limited by the risk of major bleeding, creating a substantial unmet medical need...Clinically, abelacimab demonstrated significantly lower rates of major bleeding or clinically relevant non-major bleeding compared to rivaroxaban in atrial fibrillation prophylaxis (AZALEA-TIMI 71 trial) and to enoxaparin in post-arthroplasty venous thromboembolism prevention (ANT-005 trial), establishing a favorable clinical safety profile...However, current evidence is extrapolated from AF/VTE prophylaxis studies, lacking direct human data for acute PE management. Urgent phase III trials (eg, PE-FOCUS) are therefore essential to validate efficacy and safety in acute PE, potentially redefining the anticoagulation paradigm."

Journal • Review • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Orthopedics • Pulmonary Embolism • Respiratory Diseases • Venous Thromboembolism

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

Safety of Factor XI Inhibition With Abelacimab in Atrial Fibrillation by Kidney Function: A Prespecified Analysis of the AZALEA-TIMI 71 Randomized Clinical Trial. (PubMed, JAMA Cardiol) - "In this secondary analysis of the AZALEA-TIMI 71 randomized clinical trial, abelacimab consistently reduced the risk of bleeding relative to rivaroxaban irrespective of kidney function. These findings suggest that abelacimab may offer a particularly favorable safety profile among those with chronic kidney disease; however, larger studies are necessary to characterize the efficacy of abelacimab for stroke prevention in AF."

Clinical • Journal • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

AZALEA-TIMI 71: Safety and Tolerability of Abelacimab (MAA868) vs. Rivaroxaban in Patients With Atrial Fibrillation (clinicaltrials.gov) - P2 | N=1287 | Active, not recruiting | Sponsor: Anthos Therapeutics, Inc. | Trial completion date: Dec 2025 ➔ Dec 2028

Trial completion date • Atrial Fibrillation • Cardiovascular

Renal function and factor XI inhibition in atrial fibrillation: a pre-specified analysis of AZALEA-TIMI 71 (ESC-WCC 2025) - "Patients with renal impairment are at higher risk of bleeding despite dose reduction of rivaroxaban. Abelacimab significantly reduces bleeding relative to rivaroxaban irrespective of renal function or rivaroxaban dose-reduction, with potential for greater absolute safety benefit in those with impaired renal function."

Atrial Fibrillation • Cardiovascular

Prior anticoagulation experience, bleeding risk, and safety of factor XI inhibition in atrial fibrillation: an analysis of AZALEA-TIMI 71 (ESC-WCC 2025) - "Prior OAC experience is an important indicator of bleeding risk among patients with AF. Compared with rivaroxaban, abelacimab consistently reduced the risk of bleeding irrespective of OAC experience, with potential for a greater absolute safety benefit among OAC-naïve patients."

Clinical • Atrial Fibrillation • Cardiovascular

ASTER: A Study Comparing Abelacimab to Apixaban in the Treatment of Cancer-associated VTE (clinicaltrials.gov) - P3 | N=1150 | Active, not recruiting | Sponsor: Anthos Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | N=1655 ➔ 1150

Enrollment change • Enrollment closed • Cardiovascular • Oncology • Respiratory Diseases • Venous Thromboembolism

Low concentrations of recombinant activated factor VII normalize coagulation patterns by reversing the changes in viscoelastic testing parameters induced by abelacimab in vitro. (PubMed, Res Pract Thromb Haemost) - "Low concentrations of rFVIIa (0.5-1 μg/mL) corrected the effects of abelacimab as assessed by rotational thromboelastometry. Our data support using low doses of rFVIIa for bleeding management in patients treated with abelacimab."

Journal • Preclinical

Abelacimab versus rivaroxaban in patients with atrial fibrillation: Insights into the AZALEA-TIMI 71 study. (PubMed, Rev Invest Clin) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

Abelacimab Versus Rivaroxaban in Patients With Atrial Fibrillation Receiving Oral Antiplatelet Therapy: Definitely Safe, but How Effective? (PubMed, Circulation) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular • Hematological Disorders

Protective Effects of FXI Inhibition by Abelacimab in a Baboon Model of Live Staphylococcus aureus Sepsis. (PubMed, J Thromb Haemost) - "FXI inhibition by abelacimab offers significant protection by attenuating activation of coagulation, reducing inflammation and preventing organ failure. Targeting FXI may be a promising therapeutic strategy for managing sepsis, addressing multiple facets of its complex pathophysiology."

Journal • Hematological Disorders • Infectious Disease • Inflammation • Septic Shock

Abelacimab Has Fewer Bleeds Than Rivaroxaban, But Study Has Several Important Biases. (PubMed, Am Fam Physician) - No abstract available

Journal

FXI inhibition with Abelacimab protects against S. aureus sepsis in a baboon model (ISTH 2025) - "Proteomic analysis revealed that abelacimab modulated pathways related to coagulation, inflammation, and tissue injury, contributing to improved survival. Table or Figure Upload"

Hematological Disorders • Infectious Disease • Inflammation • Septic Shock

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"

Dose optimization of abelacimab a novel fully human potent anti-FXI monoclonal antibody for patients with thromboembolic diseases (ISTH 2025) - "In the AZELEA trial, the median reduction of frFXI was 99% and this persisted for 2 years, providing confirmation of these predictions. Table or Figure Upload"

Clinical • Cardiovascular

Abelacimab Versus Rivaroxaban in Patients With Atrial Fibrillation on Antiplatelet Therapy: A Prespecified Analysis of the AZALEA-TIMI 71 Trial. (PubMed, Circulation) - P2 | "Of 1287 patients (44% female; median age, 74 years [interquartile range, 69-78]), 318 (24.7%) were on APT at baseline with planned continuation (15.5% aspirin only, 7.5% P2Y12 inhibitor only, and 1.6% dual APT). These data suggest that factor XI inhibition may be a safe anticoagulant option in patients with atrial fibrillation requiring concomitant APT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04755283."

Journal • Atrial Fibrillation • Cardiovascular • Hematological Disorders

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

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

Long-Acting Factor XI Inhibition and Periprocedural Bleeding: An Analysis From AZALEA-TIMI 71. (PubMed, J Am Coll Cardiol) - "These data illustrate that patients with AF treated with abelacimab, a long-acting factor XI inhibitor, can undergo invasive procedures with low rates of bleeding. Moreover, these findings suggest that routine interruption of anticoagulation may not be necessary for all procedures in the context of factor XI inhibition, particularly for procedures that have low bleeding risk."

Clinical • Journal • Atrial Fibrillation • Cardiovascular • Myocardial Infarction

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