abelacimab (MAA868) / Novartis - LARVOL DELTA

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

Journal

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

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

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

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"

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

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

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

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

Abelacimab: Regulatory submission for atrial fibrillation in 2027 (Novartis) - Q1 2025 Results

Filing • Atrial Fibrillation • Cardiovascular

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

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

Journal • Atrial Fibrillation • Cardiovascular

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

Journal • Atrial Fibrillation • Cardiovascular

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

Journal • Atrial Fibrillation • Cardiovascular

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

Blackstone Life Sciences and Anthos Therapeutics Announce Novartis has Completed the Acquisition of Anthos Therapeutics in a Deal Valued at up to $3.1B, with $925M Paid Upfront (Businesswire) - "Blackstone Life Sciences and Anthos Therapeutics...announced today that Novartis has completed its acquisition of Anthos Therapeutics in a transaction valued at up to $3.1 billion. Anthos was founded by Blackstone Life Sciences and Novartis in 2019 with the exclusive global rights from Novartis to develop, manufacture, and commercialize abelacimab, a novel Factor XI inhibitor that originated at Novartis. Abelacimab is currently in Phase 3 clinical development for the prevention of stroke and systemic embolism in patients with atrial fibrillation (LILAC-TIMI 76), in addition to two phase 3 studies in patients with cancer-associated thrombosis (ASTER and MAGNOLIA). Data from these trials are expected in the second half of 2026....Anthos shareholders will receive up to $3.1 billion in total deal value, including an upfront payment of $925 million, and payments in the event certain regulatory and commercial milestones are achieved."

M&A • P3 data • Atrial Fibrillation • Thrombosis • Venous Thromboembolism

BLEEDING WITH THE FXI INHIBITOR ABELACIMAB COMPARED WITH RIVAROXABAN IN OLDER INDIVIDUALS WITH ATRIAL FIBRILLATION: ANALYSIS OF THE AZALEA-TIMI 71 TRIAL - Samer Al Said (ACC 2025) - "Inhibition of FXI with abelacimab significantly reduced the relative risk of bleeding compared with RIVA regardless of age, with potential for greater absolute reductions in those age ≥75 y. These data suggest that FXI inhibitor may be especially beneficial in minimizing bleeding in older pts with AF."

Clinical • Atrial Fibrillation • Cardiovascular

FACTOR XI INHIBITION WITH ABELACIMAB IN ATRIAL FIBRILLATION ACROSS THE SPECTRUM OF BLEEDING RISK - Siddharth M. Patel (ACC 2025) - "Abelacimab reduces bleeding vs. rivaroxaban across the spectrum of bleeding risk, with greater absolute reductions in those at high bleeding risk. Emerging factor XI inhibitor therapies may be especially attractive in pts with AF at high bleeding risk."

Atrial Fibrillation • Cardiovascular

Anthos Therapeutics Shares New Data from the Landmark AZALEA-TIMI 71 Study Demonstrating the Factor XI Inhibitor Abelacimab Significantly Reduced Bleeding in Patients Regardless of Age or Bleeding Risk (GlobeNewswire) - P2 | N=1,287 | AZALEA-TIMI 71 (NCT04755283) | Sponsor: Anthos Therapeutics, Inc. | "Relevant Study Details: Both abelacimab doses (90 mg and 150 mg) were pooled for this analysis; Cox proportional hazards were used to examine the primary outcome of major/CRNM bleeding with an interaction term for treatment*age (≥75 vs <75 yrs); Of 1,287 patients, 625 (49%) were ≥75 yrs at baseline. Patients ≥75 had lower BMI (28 vs. 32 kg/m2) and were less likely to be on antiplatelet therapy (17% vs 31%), but more likely to have Creatinine clearance (CrCl) ≤50 mL/min (33% vs. 8%) compared with younger patients (p<0.001 for each)....Relevant Study Details: Both abelacimab doses (90 mg and 150 mg) were pooled for this analysis; Patient-specific bleeding risk was categorized using the previously validated DOAC score; Overall, 8%, 33%, 37%, 16% and 5% of patients were categorized as very low (0-3), low (4-5), moderate (6-7), high (8-9) and very high (10) bleeding risk, respectively."

P2 data • Atrial Fibrillation

AZALEA-TIMI 71 trial: less bleeding with abelacimab compared to rivaroxaban in atrial fibrillation, but stroke prevention is uncertain. (PubMed, Eur Heart J Cardiovasc Pharmacother) - No abstract available

Journal • Atrial Fibrillation • Cardiovascular

Blackstone Life Sciences and Anthos Therapeutics Announce Agreement for Anthos to be Acquired by Novartis for up to $3.1 Billion (Businesswire) - "Blackstone Life Sciences and Anthos Therapeutics, Inc...announced...that the company has entered into an agreement with Novartis to acquire Anthos for up to $3.1 billion...'With its deep roots in the cardiovascular space, Novartis is especially well positioned to advance abelacimab’s clinical development and bring this innovative product to healthcare providers and patients.'...Anthos is currently conducting a phase 3 clinical study in patients with atrial fibrillation with high risk for stroke or systemic embolism (LILAC-TIMI 76) as well as two phase 3 studies in patients with cancer-associated thrombosis (ASTER and MAGNOLIA). Data from these trials are expected in the second half of 2026."

M&A • P3 data • Atrial Fibrillation • Cardiovascular • Thrombosis • Venous Thromboembolism

Novartis bolsters late-stage cardiovascular pipeline with agreement to acquire Anthos Therapeutics for USD 925 million upfront (Novartis) - "Novartis today announced that it has entered into an agreement to acquire Anthos Therapeutics, Inc...a late-stage medicine in development for the prevention of stroke and systemic embolism in patients with atrial fibrillation....Under the terms of the agreement, Novartis will make an upfront payment of USD 925 million upon closing of the transaction, subject to certain customary adjustments, and potential additional payments of up to USD 2.15 billion upon achievement of specified regulatory and sales milestones. The transaction is expected to close in the first half of 2025, subject to satisfaction of customary closing conditions....Three Phase 3 clinical trials are ongoing for patients at risk of arterial and venous clots, one in patients with atrial fibrillation (LILAC-TIMI 763) and two in cancer associated thrombosis (ASTER) and (MAGNOLIA)."

M&A • Atrial Fibrillation • Cardiovascular • Thrombosis