Bevyxxa (betrixaban) / AstraZeneca - LARVOL DELTA

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

An Update on Betrixaban, The Challenging Anticoagulant Agent for Extended Venous Thromboembolism Prophylaxis. (PubMed, J Cardiovasc Pharmacol) - "The current necessity revolves around the acquisition of a substantial volume of data to dispel the uncertainties associated with this drug due to its non-approval by the EMA. Consequently, we eagerly await the results of post-marketing pharmacovigilance efforts to provide further insights into the performance of betrixaban within the broader population."

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

RISK OF DIFFUSE ALVEOLAR HEMORRHAGE WITH DIRECT ORAL ANTICOAGULANTS: A 10-YEAR RETROSPECTIVE PHARMACOVIGILANCE REPORT FROM THE FAERS DATABASE (CHEST 2023) - "The five FDA-approved DOACs available in the US (apixaban, betrixaban, dabigatran, edoxaban and rivaroxaban) were included in analysis. The main findings are DOAC-associated DAH is higher in older adults, males and frequently required hospitalization and were life threatening. Among cases reported, the most common DOAC encountered was rivaroxaban. Lastly, the fact DOACs present nearly 13-fold increase associated with DAH is an important finding and cannot be ignored."

Adverse events • Retrospective data • Atrial Fibrillation • Cardiovascular • Critical care • Hematological Disorders • Pulmonary Embolism • Respiratory Diseases • Venous Thromboembolism

An Update on Betrixaban, The Challenging Anticoagulant Agent for Extended Venous Thromboembolism Prophylaxis. (PubMed, J Cardiovasc Pharmacol) - "Despite the availability of several anticoagulant drugs like vitamin K antagonists, heparinoids, rivaroxaban, apixaban, edoxaban, and dabigatran, none of them has received approval from the US Food and Drug Administration (FDA) for long-term thromboprophylaxis. Therefore, this article aims to explore the challenges faced during the approval process of betrixaban and provide a comprehensive review of the literature on its advantages and disadvantages as a long-term prophylaxis approach for VTE. Furthermore, we aim to identify the ambiguous points that require further investigation in future studies."

Journal • Cardiovascular • Venous Thromboembolism

An Evidence-Based Approach to Anticoagulation Therapy Comparing Direct Oral Anticoagulants and Vitamin K Antagonists in Patients With Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review, Meta-Analysis, and Network Meta-Analysis. (PubMed, Am J Cardiol) - "Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban, betrixaban, and dabigatran. However, no significant difference was observed in the incidence of gastrointestinal bleeding, major bleeding, thromboembolic events, and all-cause mortality. In addition, our network MA did not identify any specific DOAC treatment as more favorable than others."

Journal • Retrospective data • Review • Atrial Fibrillation • Cardiovascular • Gastroenterology • Gastrointestinal Disorder

Investigating Betrixaban Maleate drug degradation profiles, isolation and characterization of unknown degradation products by mass-triggered preparative HPLC, HRMS, and NMR. (PubMed, J Pharm Biomed Anal) - "Based on spectral and chromatographic data, it was firmly proven that these distinct degradation products were the betrixaban chemical's hydrolysis components. The formation of the degradants has been hypothesized through several possible mechanisms."

Journal

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: Apr 2033 ➔ Aug 2033 | Trial primary completion date: Apr 2028 ➔ Aug 2028

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