abelacimab (MAA868) / Novartis - LARVOL DELTA

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

The emerging role of anticoagulants targeting factor XI in thromboembolism management. (PubMed, Expert Rev Respir Med) - No abstract available

Journal • Cardiovascular • Hematological Disorders • Oncology • Thrombosis

Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation. (PubMed, N Engl J Med) - P2 | "Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban. (Funded by Anthos Therapeutics; AZALEA-TIMI 71 ClinicalTrials.gov number, NCT04755283.)."

Clinical • Journal • Atrial Fibrillation • Cardiovascular

Data Published Today in the New England Journal of Medicine Demonstrates Anthos Therapeutics’ novel Factor XI inhibitor, Abelacimab 150mg, Reduced Major or Clinically Relevant Non-Major Bleeding by 62% Compared to Rivaroxaban (Xarelto) in Patients with Atrial Fibrillation (GlobeNewswire) - P2 | N=1,200 | AZALEA-TIMI 71 (NCT04755283) | Sponsor: Anthos Therapeutics, Inc. | "Originally presented at a late-breaking session of the 2023 American Heart Association (AHA) meeting, the NEJM publication provides more complete clinical details of the study....Study Highlights: Median 99% inhibition of Factor XI sustained over 2 years with abelacimab 150 mg dosed once monthly; 62% reduction in major or clinically relevant non-major bleeding with abelacimab 150 mg compared with rivaroxaban 20 mg in patients with AFib who are at moderate-to-high risk of stroke (P<0.001, HR 0.38, 95% Cl 0.24–0.60); 67% reduction in major bleeding alone with abelacimab 150 mg vs rivaroxaban 20 mg (P=0.001, HR 0.33, 95% CI 0.16-0.66); 89% reduction in gastrointestinal (GI) bleeding....With a median follow up of 21 months, the AZALEA-TIMI 71 Phase 2 study is the longest head-to-head study to date of a Factor XI inhibitor..."

P2 data • Atrial Fibrillation

New Targets for Antithrombotic Medications: Seeking to Decouple Thrombosis from Hemostasis. (PubMed, J Thromb Haemost) - "Among the factor XI/XIa inhibitors of coagulation, a parenterally administered monoclonal antibody (abelacimab) and two orally administered small molecule inhibitors (asundexian, milvexian) are collectively being studied in patients with atrial fibrillation, cancer-associated venous thromboembolism, acute coronary syndrome, and ischemic stroke. One parenterally administered glycoprotein VI antiplatelet agent (glenzocimab) is currently being studied in patients with ischemic stroke. If shown to be efficacious and safe in ongoing phase 3 studies, both classes of emerging antithrombotic agents have the potential to greatly improve outcomes for patients with challenging thrombotic conditions."

Journal • Review • Acute Coronary Syndrome • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Ischemic stroke • Nephrology • Oncology • Renal Disease • Thrombosis • Venous Thromboembolism

Bleeding with the FXI Inhibitor Abelacimab compared with Rivaroxaban in Patients on Antiplatelet therapy: A Prespecified Analysis of the AZALEA-TIMI 71 Trial (AHA 2024) - "The primary outcome, major or clinically relevant non-major (CRNM) bleeding, was compared using Cox proportional hazards adjusted for age, sex, and BMI, with an interaction term for randomized treatment and APT use.Of 1,287 patients, 318 (25%) were on APT at baseline (16% aspirin only, 8% P2Y12 only, 2% DAPT) and were younger (median age 72 vs 75 years) and had a higher prevalence of CAD (74% vs 40%), prior MI (36% vs 16%) and PAD (15% vs 11%) than those not on APT (p<0.05 for each). Inhibition of FXI with abelacimab results in substantial reductions in bleeding compared with rivaroxaban regardless of concomitant APT use. These data support the potential advantage of FXI inhibitors in patients who require concomitant APT."

Clinical • Atrial Fibrillation • Cardiovascular

The factor XI/XIa antibody abelacimab combined with enoxaparin inhibits filter clotting in hemodialysis circuits ex vivo. (PubMed, J Thromb Thrombolysis) - "This is an aggressive model due to the frequent re-circulation of blood and a lack of endothelial cells. These data provide support for testing abelacimab in patients on hemodialysis."

Journal • Preclinical • Thrombosis

MAGNOLIA: A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE (clinicaltrials.gov) - P3 | N=1020 | Recruiting | Sponsor: Anthos Therapeutics, Inc. | Trial completion date: Sep 2025 ➔ Feb 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Cardiovascular • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Oncology • Respiratory Diseases • Solid Tumor • Venous Thromboembolism

Abelacimab for the Treatment of Stroke Prevention in Atrial Fibrillation (SPAF): An Early Cost-Effectiveness Analysis (CEA) Versus Rivaroxaban from 5 European Country Perspectives (ISPOR-EU 2024) - "This is the first analysis assessing the potential cost-effectiveness of abelacimab, an investigational once-monthly, Factor XI inhibitor for people with AF at moderate-to-high risk of stroke, from five European country perspectives. If approved, abelacimab could yield substantial cost savings."

Cost effectiveness • HEOR • Atrial Fibrillation • Cardiovascular • Myocardial Infarction

Anthos Therapeutics Shares New Analysis from the Landmark AZALEA-TIMI 71 Study Demonstrating the Factor XI Inhibitor Abelacimab Substantially Reduced Bleeding in Patients on Antiplatelet Therapy Compared to Rivaroxaban (GlobeNewswire) - P2 | N=1200 | AZALEA-TIMI 71 (NCT04755283) | Sponsor: Anthos Therapeutics, Inc. | "Anthos Therapeutics, Inc...presented new data today at the American Heart Association (AHA) Scientific Sessions from its landmark AZALEA-TIMI 71 study that demonstrated the novel factor XI inhibitor abelacimab led to consistent and substantial reductions in bleeding for patients on or off antiplatelet (APT) therapy, as compared to rivaroxaban....The data demonstrate a 67% reduction in bleeding for patients on APT taking abelacimab 150 mg compared to patients taking rivaroxaban (a 10.6% incidence rate for rivaroxaban to a 3.5% incidence rate for abelacimab 150 mg). As expected, the absolute rate of bleeding observed was higher when rivaroxaban was combined with APT vs. rivaroxaban alone (10.6% vs. 7.7%). However, the rate of bleeding in patients treated with abelacimab 150 mg was similar, regardless of APT use (3.5% abelacimab with APT vs 3.1% abelacimab alone)."

P2 data • Atrial Fibrillation • Thrombosis

ASTER: A Study Comparing Abelacimab to Apixaban in the Treatment of Cancer-associated VTE (clinicaltrials.gov) - P3 | N=1655 | Recruiting | Sponsor: Anthos Therapeutics, Inc. | Trial completion date: Sep 2025 ➔ Feb 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Cardiovascular • Hematological Disorders • Oncology • Respiratory Diseases • Venous Thromboembolism

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=1900 | Recruiting | Sponsor: Anthos Therapeutics, Inc. | Trial completion date: Mar 2025 ➔ Oct 2026 | Trial primary completion date: Jan 2025 ➔ Aug 2026

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

Anthos Therapeutics Unveils Additional Analysis from the Landmark AZALEA-TIMI 71 Study Demonstrating that the Factor XI Inhibitor Abelacimab was Associated with Remarkably Low Levels of Periprocedural Bleeding in Patients with Atrial Fibrillation (Businesswire) - P2 | N=1,200 | AZALEA-TIMI 71 (NCT04755283) | Sponsor: Anthos Therapeutics, Inc. | "Anthos Therapeutics...announced today, at a late-breaking session of the European Society for Cardiology (ESC) Congress, a new analysis from the landmark AZALEA-TIMI 71 study, demonstrated that approximately 1% of patients randomized to abelacimab, an investigational Factor XI inhibitor, experienced a major or clinically relevant non-major procedural bleed while undergoing invasive procedures....'The potential with abelacimab to no longer need to stop and restart treatment will minimize stress for the very large number of atrial fibrillation patients who undergo a broad range of procedures each year.'...Assessed at the procedure level, 14 procedure-related major/CRNM bleeds occurred, 1.2% of all procedures in the abelacimab arms vs. 2.2% of all procedures in the rivaroxaban arm (RR 0.54 [95% CI, 0.19-1.58])."

P2 data • Atrial Fibrillation