Bevyxxa (betrixaban) / AstraZeneca - LARVOL DELTA

Identification of Der p1 inhibitors: Combining AI-based QSAR, molecular docking, molecular dynamics simulations and quantum physics. (PubMed, Comput Biol Chem) - "Molecular docking results revealed that the top three docking scores were -25.5456, -20.6206 and -19.9821 kcal/mol for betrixaban, ceritinib and ivacaftor, respectively. The integrated computational workflow identified Betrixaban as the most promising FDA-approved candidate for Der p1 inhibition based on its favorable overall binding affinity and stable protein complex, while Ceritinib demonstrated superior electronic interactions and hydrogen-bond stability that may support future lead optimization. These findings provide a rational framework for drug repurposing against Der p1 and warrant further experimental validation through biochemical and cellular assays."

Journal • Allergy • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Integrated machine learning and molecular dynamics-driven multi-target virtual screening of FDA-approved drugs for drug repurposing in breast cancer. (PubMed, In Silico Pharmacol) - "Ponatinib emerged as the top-ranked computational candidate (mean: - 10.07 kcal/mol), followed by Regorafenib (- 9.64), Sorafenib (- 9.46), and Entrectinib (- 9.45), while non-oncology drugs including antrafenine, betrixaban, and maraviroc demonstrated novel multi-target binding profiles...MM-GBSA calculations revealed a binding hierarchy concordant with docking scores (R2 = 0.92): Ponatinib-VEGFR2 (ΔGbind = - 42.38 kcal/mol) > Entrectinib-CDK6 (- 38.56) > Ponatinib-EGFR (- 33.24) > Entrectinib-HER2 (- 28.47) > Dacomitinib-HDAC3 (- 24.63 kcal/mol)...As the present study is entirely computational, the identified compounds should be regarded as hypothesis generating leads requiring experimental validation through in vitro kinase and HDAC3 inhibition assays, cell based studies, and target engagement confirmation before any translational conclusions can be drawn. The online version contains supplementary material available at..."

FDA event • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK6 • EGFR • HDAC3 • HER-2 • KDR

Betrixaban for Deep Venous Thrombosis Prevention in a Patient with End-Stage Renal Disease on Intermittent Hemodialysis. (PubMed, J Biosci Med (Irvine)) - "This case report demonstrates the successful use of betrixaban without accumulation for a patient with ESRD on HD. Betrixaban may be a potential choice when standard options are unsuitable for VTE prophylaxis or in patients with contraindications to other treatments."

Journal • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • Thrombocytopenia • Thrombosis • Venous Thromboembolism

Residue‑resolved dynamically averaged interaction analysis of direct factor Xa inhibitors by MD‑FMO combination calculations. (PubMed, J Comput Aided Mol Des) - "Four widely used direct oral anticoagulants (DOACs)-Edoxaban, Betrixaban, Apixaban, and Rivaroxaban-inhibit factor Xa, a key enzyme in the blood coagulation cascade. As a result, Cys191, Tyr99, Trp215, Glu217, Phe174, and Gln192 were identified as major contributive residues across the four ligands, with cooperative stabilization arising from electrostatic, charge-transfer, and dispersion components. The influence of protonation (charged states) was also examined for Edoxaban and Betrixaban."

Journal

Betrixaban activates cGAS-STING to promote antitumor immunity without pathological inflammation. (PubMed, EMBO Mol Med) - "Mechanistically, BT induced a noncanonical, DNA-independent activation of the cGAS-STING pathway, triggering type I interferon signaling without provoking a full inflammatory cascade. These findings highlighted BT as a strategy to promote antitumor immunity while restraining inflammation, potentially improving cancer immunotherapy with reduced inflammatory toxicity."

Journal • Infectious Disease • Oncology • Septic Shock • CD8 • STING

Betrixaban activates cGAS and ERVs to promote dual nucleic-sensing antiviral immunity. (PubMed, EMBO Mol Med) - "These combined signal cascades triggered strong type I interferon responses and conferred broad-spectrum antiviral protection against RNA and DNA viruses in vitro and in vivo. These findings unveil a unique host-directed antiviral strategy wherein a small-molecule drug engages dual nucleic acid-sensing pathway, and suggest repurposing BT as an orally broad-spectrum antiviral."

Journal • IFIH1

30 years of classical hematology drugs in the US: Approvals, costs, and sales (ASH 2025) - "Six drugs have been discontinued (year approved/year discontinued/reason): betrixaban(2017/2020/business), daprodustat (2023/2024/business), fidanacogene elaparvovec(2024/2025/business), oprelvekin (1997/2011/business), peginesatide (2012/2013/safety), and voxelotor(2019/2024/safety).There are limitations to our study. Some drugs have non-classical hematology indications (anticoagulantsin atrial fibrillation; luspatercept in myelodysplastic neoplasm) and/or may also be prescribed by non-classical hematologists (erythropoiesis stimulating agents by nephrologists and medical oncologists)...Classical hematology drugs contribute substantially to US prescription drug spending, with over $70billion in annual sales and medications for thromboembolism accounting for over half of the costs.Approvals have accelerated over the past three decades, doubling each decade. Biologics and biosimilarsnow represent two-thirds of approvals. Continuous-duration treatments, particularly for..."

Anemia • Atrial Fibrillation • Beta-Thalassemia • Cardiovascular • Chemotherapy-Induced Neutropenia • Chronic Kidney Disease • Complement-mediated Rare Disorders • Gene Therapies • Genetic Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hemophilia • Immune Thrombocytopenic Purpura • Immunology • Myelodysplastic Syndrome • Nephrology • Neutropenia • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Sickle Cell Disease • Thrombocytopenia • Thrombocytopenic Purpura

Clinical laboratory testing of blood from patients presenting to the emergency department with acute bleeding due to factor Xa inhibitors: An unmet medical need. (PubMed, Clin Chim Acta) - "For patients on warfarin, stat testing of blood for the prothrombin time and calculation of the International Ratio (PT-INR) are used to determine if acute bleeding is caused by excess anticoagulation. Direct acting oral anticoagulants (DOACs) include those that inhibit Factor Xa (apixaban, rivaroxaban, edoxaban, and betrixaban) or Factor IIa (dabagatran)...However, current laboratory assays for anti-Factor Xa are calibrated for the specific DOAC used and results are not typically available in emergency departments. Therefore, there is a need to produce a rapid bedside blood test that can detect bleeding to any DOAC drug that was prescribed."

Journal • Cardiovascular • Ischemic stroke

Analyzing the Rates of Heavy Menstrual Bleeding By Anticoagulant Type in Menstruating Individuals: A Large National Database Study (ASH 2024) - "Patients on Betrixaban and Edoxaban were not analyzed due to their small sample size. Our results showed that prevalence of HMB was lowest among patients on Lovenox compared to warfarin, rivaroxaban, apixaban and dabigatran (p<0.05)...Conclusion : Our study demonstrates that patients on anticoagulants have a significant risk of HMB, emphasizing the importance of careful patient history and follow-up for HMB assessment. If HMB is present, anticoagulants with lower rates of HMB should be preferred."

Clinical • Hematological Disorders • Hemophilia • Rare Diseases • Thrombocytopenia • Women's Health

CORRAL-AF: Can the Lambre Device Occlude IRRegular And Large Appendages in Patients With Non-Valvular AF (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Brian O'Neill MD | N=2931 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombosis

Intracranial Hemorrhage With Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin in Brain Tumors: A Review and Meta-Analysis. (PubMed, Neurology) - "In the current meta-analysis, DOACs were associated with significantly lower ICH risk than LMWH in patients with anticoagulated brain tumor, particularly those with primary brain tumors. Findings support DOACs as a safe anticoagulant in arterial and venous thromboembolism. Given observational designs with inherent confounding, findings warrant cautious interpretation."

Journal • Retrospective data • Brain Cancer • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Oncology • Solid Tumor • Venous Thromboembolism

Hemorrhage Risk Associated with Anticoagulant and Antiplatelet Drug Combinations: Insights from the USFDA Adverse Event Reporting System. (PubMed, J Clin Med) - "Anticoagulants analyzed included warfarin, rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, and acenocoumarol; antiplatelets included aspirin, clopidogrel, ticagrelor, cilostazol, prasugrel, and dipyridamole. While our findings highlight potential safety signals related to hemorrhage with antithrombotic drug combinations, they remain hypothesis-generating and should not be interpreted as causal associations. Instead, they provide an initial basis for further validation in well-designed clinical cohorts where comorbidities can be adequately accounted for."

Adverse events • Journal • Hematological Disorders

Betrixaban is a broad anti-virus inhibitor by activating innate immunity. (PubMed, Front Cell Infect Microbiol) - "In vivo, BT treatment markedly induced IFNB1 expression across multiple mouse tissues and significantly inhibited viral replication in VSV-infected wild-type mice, confirming the essential role of innate antiviral immune activation. These findings establish BT as a potent stimulator of the innate immune system, demonstrating broad-spectrum antiviral potential and highlighting its promise as a therapeutic agent."

Journal • Cardiovascular • CNS Disorders • Herpes Simplex • Infectious Disease • Inflammation • Influenza • Respiratory Diseases • IFNB1

Herb-Drug Interaction Between Sailuotong and Pitavastatin: A Systematic Pharmacokinetic Investigation and Mechanism Analysis. (PubMed, Drug Des Devel Ther) - "Transporter functionality was validated using MDR1 substrates (digoxin and betrixaban). Combining SLT and PIV can lead to HDIs, with multiple doses of SLT significantly reducing the plasma and hepatic exposure of PIV in rats. The primary mechanism appears to be the induction of the intestinal efflux transporter MDR1, resulting in decreased bioavailability of PIV."

Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Dementia • ABCB1

Predicting drug-drug interactions and optimal dosing of betrixaban with physiologically based pharmacokinetic modeling in patients with renal impairment who were coadministered with P-glycoprotein inhibitors. (PubMed, J Int Med Res) - "ObjectiveTo optimize dosing adjustments in patients with renal impairment who were coadministered with P-glycoprotein inhibitors-verapamil or amiodarone-using a physiologically based pharmacokinetic model.MethodsThe developed physiologically based pharmacokinetic model was corroborated using previously reported pharmacokinetic parameters across multiple doses, ratio values in drug-drug interactions, and pharmacokinetic ratio values in patients with renal impairment.ResultsThe physiologically based pharmacokinetic model exhibited fold errors between 0.7 and 1.3 and effectively illustrated changes in pharmacokinetic ratios in patients with renal impairment. For patients with severe renal impairment, it may be reasonable to avoid concurrent use of betrixaban with P-glycoprotein inhibitors.ConclusionsThe coadministration of P-glycoprotein inhibitors elevates the exposure of betrixaban and may heighten the risk of major bleeding. Reduced dosing regimens are recommended for..."

Journal • PK/PD data • Renal Disease

Interrupted versus uninterrupted anticoagulation for cardiac rhythm management device insertion. (PubMed, Cochrane Database Syst Rev) - "Interrupted anticoagulation in people undergoing elective CIED surgery had similar outcomes to uninterrupted anticoagulation with either warfarin or DOAC medications. Certainty of evidence was judged to be low to very low for most of the assessed outcomes. Further RCTs are particularly needed to help identify whether IAC significantly impacts the risks of thromboembolic events and device-pocket hematoma."

Clinical • Journal • Review • Cardiovascular • Hematological Disorders • Ischemic stroke • Pulmonary Embolism • Respiratory Diseases

Biomarker Stratified CaboZantinib and NivOlumab (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants with Advanced Solid Tumors (IO refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study (SWOG-Fall 2024) - "Participants must not require concomitant anticoagulation with coumarin agents, direct thrombin inhibitors, direct factor Xa inhibitor betrixaban, or platelet inhibitors...Feasibility interim analysis for the primary endpoint will be evaluated at the end of Stage I. Interim futility analyses for the ORR are also planned. Summary Statement For the current status of this study, please refer to the Precision Medicine chapter."

Biomarker • Clinical • IO biomarker • Metastases • P2 data • Tumor mutational burden • Cardiovascular • Eye Cancer • Gastrointestinal Disorder • Head and Neck Cancer • Hematological Disorders • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TMB

Extended Sulfo-Pillar[6]arenes ─ a New Host Family and Its Application in the Binding of Direct Oral Anticoagulants. (PubMed, J Am Chem Soc) - "This new functionality enables more noncovalent interactions and strong affinity toward guests, which we demonstrate using the direct oral anticoagulants (DOACs) dabigatran, betrixaban, and edoxaban. This functionalization also introduces new fluorescent properties to the sulfo-pillar[6]arene family via an incorporated p-terphenyl (A1A2sP6). We show that these new hosts have ultrahigh affinity toward dabigatran (Kd = 27 nM, A1A2sP6) in salty solutions and that the A1A2sP6 analogue can bind betrixaban in bovine plasma with a physiologically relevant Kd (7 μM)."

Journal • Thrombosis

Epidemiology of pulmonary embolism diagnosis and management among United States emergency departments over an eight-year period. (PubMed, Am J Emerg Med) - "This study highlights significant shifts in the epidemiology and management of PE within the ED setting. Overall rates of PE rose, while a larger proportion were discharged. Direct oral anticoagulants have become the predominant therapy with the majority of patients receiving apixaban. Thrombolytic use occurs in a small subset and has been declining over time. CTPA rates have risen, while the overall diagnostic yield has declined."

Journal • Cardiovascular • Pulmonary Embolism • Respiratory Diseases • Venous Thromboembolism

CORRAL-AF: Can the Lambre Device Occlude IRRegular And Large Appendages in Patients With Non-Valvular AF (clinicaltrials.gov) - P=N/A | N=2931 | Not yet recruiting | Sponsor: Brian O'Neill MD | Trial completion date: Dec 2033 ➔ Dec 2034 | Trial primary completion date: Dec 2028 ➔ Dec 2029

Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombosis

Biomarker Stratified CaboZantinib and NivOlumab (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants with Advanced Solid Tumors (IO refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers (An immunoMATCH Pilot Study) (SWOG-Spring 2024) - "Participants must not require concomitant anticoagulation with coumarin agents, direct thrombin inhibitors, direct factor Xa inhibitor betrixaban, or platelet inhibitors...There was one treatment related death due to oral hemorrhage. There were no Grade 4 treatment-related toxicities."

Biomarker • Clinical • IO biomarker • Metastases • P2 data • Tumor mutational burden • Cardiovascular • Eye Cancer • Gastrointestinal Disorder • Head and Neck Cancer • Hematological Disorders • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TMB

Novel Thiourea and Oxime Ether Isosteviol-Based Anticoagulants: MD Simulation and ADMET Prediction. (PubMed, Pharmaceuticals (Basel)) - "It is reversibly inhibited by nonvitamin K antagonist oral anticoagulants (NOACs) such as apixaban, betrixaban, edoxaban, and rivaroxaban. One of these derivatives, E24, displays favorable pharmacokinetic properties, positioning it as the most promising drug candidate. This, along with the other three derivatives, can undergo further chemical synthesis and bioassessment."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Study Evaluating Betrixaban in Pediatric Participants (clinicaltrials.gov) - P1 | N=21 | Terminated | Sponsor: Alexion Pharmaceuticals, Inc. | Completed ➔ Terminated; After completion of Part 1 and prior to initiating Part 2, the Sponsor decided to cease developing betrixaban, prompting early study closure.

Trial termination • Pediatrics

CORRAL-AF: Can the Lambre Device Occlude IRRegular And Large Appendages in Patients With Non-Valvular AF (clinicaltrials.gov) - P=N/A | N=2931 | Not yet recruiting | Sponsor: Brian O'Neill MD | Trial completion date: Aug 2033 ➔ Dec 2033 | Trial primary completion date: Aug 2028 ➔ Dec 2028

Trial completion date • Trial primary completion date • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombosis

Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab (NSC#748726) (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants with Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study. (SWOG-Fall 2023) - "Participants must not require concomitant anticoagulation with coumarin agents, direct thrombin inhibitors, direct factor Xa inhibitor betrixaban, or platelet inhibitors...Feasibility interim analysis for the primary endpoint will be evaluated at the end of Stage I. Interim futility analyses for the ORR are also planned. Summary Statement For the current status of this study, please refer to the Precision Medicine chapter."

Biomarker • Clinical • IO biomarker • Metastases • P2 data • Tumor mutational burden • Cardiovascular • Eye Cancer • Gastrointestinal Disorder • Head and Neck Cancer • Hematological Disorders • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TMB