- |||||||||| montelukast / Generic mfg.
Preclinical, Journal: Discovery of the Low-Hemorrhagic Antithrombotic Effect of Montelukast by Targeting FXIa in Mice. (Pubmed Central) - Mar 27, 2025
Moreover, combination therapy with MK enhanced the antithrombotic effects of antiplatelets without an obvious increase of hemorrhage. This proof-of-concept study suggests the potent low-hemorrhage antithrombotic effect of MK by targeting FXIa and unveiling a new therapeutic application of MK.
- |||||||||| Undisclosed FXIa Inhibitor / University of California, Pfizer, warfarin / Generic mfg.
Review, Journal: Anticoagulation Management: Current Landscape and Future Trends. (Pubmed Central) - Mar 17, 2025
The introduction of warfarin in the 1950s revolutionized anticoagulation by offering long-term oral regimens...This review highlights the ongoing innovation in anticoagulant development, the need for precise management, and potential future avenues like factor XIa inhibitors. Additionally, artificial intelligence holds promise for improving patient outcomes and addressing the complexities of thrombotic disease management by personalizing therapy and reducing bleeding risks.
- |||||||||| Journal: Novel factors affecting fibrin clot formation and their clinical implications. (Pubmed Central) - Dec 19, 2024
These factors have been shown to be not only associated with ischemic stroke, myocardial infarction, pulmonary embolism, and cardiovascular death, but also with unfavorably altered fibrin clot characteristics, which underscores clinical relevance of fibrin clot properties. Given preclinical or ongoing studies aimed at modifying some of these factors, in particular FXI / FXIa inhibitors, recent findings might expand our knowledge on fibrin-related mechanisms of emerging therapeutic agents tested and stimulate further research into new targets for future therapeutic interventions to prevent thromboembolic events.
- |||||||||| milvexian (BMS-986177) / BMS, J&J
Reversal of the Anticoagulant Effect of Milvexian By 4-Factor PCC and rFVIIa in Healthy Participants (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_6790;
Discussion/Conclusion : Anticoagulant effect of milvexian was successfully reversed by two commonly available, non-specific reversal agents - 4F-PCC and a low dose of rFVIIa. This may provide clinicians with additional data to assess treatment options in cases of active bleeding or the need for urgent surgical interventions in patients treated with milvexian.
- |||||||||| Praxbind (idarucizumab) / Boehringer Ingelheim, AndexXa (coagulation factor Xa (recombinant), inactivated -zhzo) / Daiichi Sankyo, AstraZeneca
Clinical guideline, Journal: Reversal of direct oral anticoagulants: Guidance from the SSC of the ISTH: R1. (Pubmed Central) - Sep 21, 2024
The established method provides a key technique for the sensitive detection, high-throughput analysis, and screening of the FXIa inhibitors. Andexanet
- |||||||||| asundexian (BAY 2433334) / Bayer, milvexian (BMS-986177) / BMS, J&J
Journal: Laboratory Evaluation of Interferences Associated with Factor XIa Inhibitors Asundexian and Milvexian in Routine Coagulation Assays. (Pubmed Central) - Sep 14, 2024
Asundexian and milvexian induce concentration-dependent prolongations in APTT-based assays with curvilinear regressions, which may be suitable for the measurement of pharmacodynamic effects at peak levels ex vivo. We also report differential sensitivities of APTT-based assays-particularly at higher FXIa inhibitor concentrations-highlighting the clinical need for an extensive evaluation of interferences associated with FXIa inhibitors in coagulation assays.
- |||||||||| milvexian (BMS-986177) / BMS, J&J
Review, Journal: Milvexian: evaluating the factor XIa inhibitor for the treatment of acute coronary syndrome. (Pubmed Central) - Aug 20, 2024
The ongoing LIBREXIA-ACS trial is the large-scale study currently investigating milvexian in patients with ACS. This study may support the proof of concept of differentiating physiological hemostasis and pathological thrombosis and achieving maximum antithrombotic efficacy with minimum bleeding risk when used on top of DAPT with potent P2Y12 receptor blockers.
- |||||||||| asundexian (BAY 2433334) / Bayer
Clinical, PK/PD data, Journal: Pharmacokinetics, pharmacodynamics, and safety of asundexian in healthy Chinese and Japanese volunteers, and comparison with Caucasian data. (Pubmed Central) - Jul 31, 2024
Asundexian induced dose-dependent prolongation of activated partial thromboplastin time and inhibition of FXIa activity, with no effects on prothrombin time or FXI concentration in Japanese participants. There were no clinically relevant interethnic differences in PK profile across the Japanese, Chinese, and Caucasian (data from the previous phase I study) participants and no clinically relevant difference in PD response between Japanese and Caucasian participants.
- |||||||||| Journal: Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect. (Pubmed Central) - Jul 5, 2024
Here, analyses of activated partial thromboplastin time (aPTT) in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identify synergistic anticoagulation effects. Both an FeCl3-induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery (tMCAO) mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.
- |||||||||| asundexian (BAY 2433334) / Bayer, milvexian (BMS-986177) / BMS, J&J, abelacimab (MAA868) / Anthos Therap, Novartis, MorphoSys, Lonza
Journal: Factor XI inhibition in patients with acute coronary syndrome. (Pubmed Central) - Jun 13, 2024
The data on efficacy, however, showed neutral results, but it should be noted that the study did not have the adequate statistical power to evaluate this outcome. Valuable information could, therefore, derive in the future from the ongoing Phase 3 trial with milvexian, LIBREXIA-ACS (A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome) and from any future studies that could be started by testing different molecules.
- |||||||||| asundexian (BAY 2433334) / Bayer
Journal: Hemorrhagic Transformation in Noncardioembolic Acute Ischemic Stroke: MRI Analysis From PACIFIC-STROKE. (Pubmed Central) - May 24, 2024
In the phase 2 PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), asundexian, an oral factor XIa inhibitor, did not increase the risk of hemorrhagic transformation (HT)...About 28% of patients with noncardioembolic stroke had early HT, and 24% had late HT detectable by MRI. Given the high frequency of HT on MRI, more research is needed on how it influences treatment decisions and outcomes.
- |||||||||| PREVALENCE AND VENOUS THROMBOTIC RISK OF ARG67STOP POLYMORPHISM IN THE PROTEIN Z-DEPENDENT PROTEASE INHIBITOR () - May 15, 2024 - Abstract #EHA2024EHA_3312;
In our experience,the thrombotic profile observed** in heterozygous carriers of the SERPINA10 67Arg>Stop is fundamentallyvenous: recurrent lower limb DVT and isolated PE; these patients seem to be at greater risk of developing VTEfrom the age of 45 and when multiple CVD risk factors are present; however, no connection was found withother acquired or hereditary VTE risk factors, unlike what has been observed in other publications. Furtherstudies with an adequate number of patients are required for a better characterisation of the thromboticprofile of the carriers of this polymorphism.
- |||||||||| FXIa inhibition (Belgrade) - May 14, 2024 - Abstract #ESC2024ESC_1026;
- |||||||||| fondaparinux / Generic mfg., argatroban / Generic mfg.
Journal: New anticoagulants in 2024: Development of factor XI and XIa inhibitors (Pubmed Central) - Apr 23, 2024
Epidemiological and preclinical data on FXI deficiency make FXI a promising therapeutic target. The aim of this review is to summarize the results of the various clinical trials available that focus on FXI/FXIa inhibition, and to highlight the challenges that this new therapeutic class of anticoagulants will face.
- |||||||||| frunexian (EP-7041 Intravenous) / eXIthera Pharma
P1 data, PK/PD data, Journal: Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study. (Pubmed Central) - Apr 5, 2024
The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers...The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300?ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.
- |||||||||| abelacimab (MAA868) / Anthos Therap, Novartis, MorphoSys, Lonza
Review, Journal: Abelacimab: A leap forward in anticoagulation with FXI and FXIa Inhibition. (Pubmed Central) - Mar 28, 2024
The current evidence supporting its use and potential future research strengthening its position in anticoagulant therapy is also discussed. The objective is to enhance understanding and contribute to discussions around developing safer anticoagulants, particularly for patients at risk for thrombosis.
- |||||||||| STATE OF THE ART ON FXI AND FXII INHIBITOR DATA (Sheraton Ballroom IV-V; Virtual) - Mar 2, 2024 - Abstract #THSNA2024THSNA_156;
Milvexian will also be compared with a placebo on top of antiplatelet therapy in patients with acute coronary syndrome (ACS) in the LIBREXIA-ACS trial. These trials, which will enroll about 78,000 subjects, will determine the future of FXI
- |||||||||| warfarin / Generic mfg.
Journal: Targeting Factor XI and Factor XIa to Prevent Thrombosis. (Pubmed Central) - Dec 24, 2023
Direct oral anticoagulants (DOACs) that inhibit the coagulation proteases thrombin or factor Xa have replaced warfarin and other vitamin K antagonists (VKA) for most indications requiring long-term anticoagulation...Based on these early results, phase 3 trials have been initiated that compare drugs targeting FXI and FXIa to standard treatments or placebo. Here we review the contributions of FXI to normal and abnormal coagulation and discuss results from pre-clinical, nonclinical, and clinical studies of FXI and FXIa inhibitors.
- |||||||||| Review, Journal: Unresolved issues in the use of direct acting oral anticoagulants. (Pubmed Central) - Dec 17, 2023
Impediments to use include concerns for bleeding and cost. The newly developed FXIa and FXIIa inhibitors have the potential to be safer than current anticoagulants, but phase 3 trials are needed to confirm their clinical efficacy and safety.
- |||||||||| Kalbitor (ecallantide) / Takeda
Journal: Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis. (Pubmed Central) - Nov 28, 2023
The newly developed FXIa and FXIIa inhibitors have the potential to be safer than current anticoagulants, but phase 3 trials are needed to confirm their clinical efficacy and safety. Here, we designed the FXIa inhibitory peptide DX-88mut by replacing Loop1 (DGPCRAAHPR) and Loop2 (IYGGC) in DX-88, which is a clinical drug targeting PKa for the treatment of hereditary angioedema, using Loop1 (TGPCRAMISR) and Loop2 (FYGGC) in the FXIa inhibitory peptide PN2KPI, respectively...Additionally, DX-88mut did not show a significant bleeding risk at a dose of 5
- |||||||||| BMS-262084 / BMS, Innohep (tinzaparin) / LEO Pharma
Effect of factor XI/XIa inhibition in an in-vitro model of tumor cell-induced coagulation activation (X1) - Sep 30, 2023 - Abstract #DGHO2023DGHO_903;
In this entity, however, dysregulated FXI synthesis can contribute to a hypercoagulable state and may critically affect the efficacy of FXI/FXIa-directed anticoagulation. Taken together, our study indicates that FXI/FXIa inhibition might be a promising approach in CAT prophylaxis and treatment, especially in tumors with weak TF PCA expression.
- |||||||||| Factor XI - From Bleeding to Thrombosis (Room 31 (San Diego Convention Center)) - Sep 23, 2023 - Abstract #ASH2023ASH_159;
In patients with cardiovascular disease, FXIa inhibition caused less clinically significant bleeding than direct oral anticoagulants and did not appear to increase bleeding when superimposed on anti-platelet therapy. Eight phase 3 trials involving nearly 80,000 patients are currently underway to establish the efficacy of FXI/FXIa inhibition compared to current standards of care in a variety of clinical situations.
- |||||||||| asundexian (BAY 2433334) / Bayer, milvexian (BMS-986177) / BMS, J&J
Review, Journal: Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis. (Pubmed Central) - Jul 20, 2023
Other orally active FXIa inhibitors also produce antithrombotic activity in vivo with low bleeding risk. Therefore, FXIa inhibitors might represent a new class of direct-acting oral anticoagulants (DOACs) for the treatment of thrombosis, although the explicit clinical positions of asundexian and milvexian in patients with ischemic stroke, high-risk TIA, and coronary artery disease require confirmation from the outcomes of ongoing phase 3 trials.
- |||||||||| enoxaparin sodium / Generic mfg.
Review, Journal: Factor XIa Inhibitors as a Novel Anticoagulation Target: Recent Clinical Research Advances. (Pubmed Central) - Jun 28, 2023
SHR2285 exhibited a predictable pharmacokinetic profile and an exposure-related pharmacodynamic profile. Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants.
- |||||||||| Review, Journal: News at XI: Moving Beyond Factor Xa Inhibitors. (Pubmed Central) - Jun 19, 2023
Currently available DOACs include dabigatran, which inhibits thrombin, and apixaban, edoxaban, and rivaroxaban, which inhibit factor (F) Xa...These new DOACs, which include asundexian and milvexian, inhibit FXIa, which is positioned in the intrinsic pathway of coagulation...These include fesomersen, an antisense oligonucleotide that reduces the hepatic synthesis of FXI, abelacimab, an antibody that binds FXI and blocks its activation, and osocimab, an FXIa inhibitory antibody. Focusing on these new agents, this paper (a) describes the unmet needs in oral anticoagulation therapy, (b) explains why FXI is a promising target for new oral anticoagulants, (c) reviews the phase 2 clinical data with the new agents and describes the ongoing phase 3 trials, and (d) provides perspective on the opportunities and challenges for FXI inhibitors.
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