- |||||||||| Review, Journal: Therapeutic Potential of FXI Inhibitors: Hype or Hope? (Pubmed Central) - Sep 28, 2024
Moreover, the largest phase 3 randomized trial designed to test the efficacy of asundexian over apixaban in patients with atrial fibrillation, the OCEANIC-AF, has been prematurely stopped as a result of the inferior efficacy of asundexian. In this review we discuss the pharmacological properties and available evidence generated thus far for factor XI inhibitors, providing a perspective on the current state of these drugs.
- |||||||||| fesomersen (IONIS-FXI-LRx) / Ionis, IONIS-FXIRx / Bayer, osocimab (BAY 1213790) / Bayer
Safety of factor XI inhibitors in patients with end-stage kidney disease on hemodialysis: A meta-analysis of randomized controlled trials (Plenary Hall) - May 17, 2024 - Abstract #ISTH2024ISTH_1949;
Of those, one study was still ongoing, resulting in five studies investigating FXI inhibitors (IONIS-FXIRx, xisomab, fesomersen, osocimab) encompassing 1,270 patients included in our meta-analysis (table). FXI inhibitors were associated with an OR of 0.80 (95% CI, 0.49-1.32) for the occurrence of CRB compared to placebo (Fig.).
- |||||||||| Review, Journal: Drug-Drug Interactions of FXI Inhibitors: Clinical Relevance. (Pubmed Central) - Mar 27, 2024
These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.
- |||||||||| Retrospective data, Review, Journal: Factor XI inhibitors in early clinical trials: a meta-analysis. (Pubmed Central) - May 25, 2023
?Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy.
- |||||||||| Factor XI inhibitors in early clinical trials: a meta-analysis (Station 9) - May 13, 2023 - Abstract #ESC2023ESC_3856;
Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy.
- |||||||||| Journal: Pharmacotherapy for stroke prevention in nonvalvular atrial fibrillation: current strategies and future directions. (Pubmed Central) - Nov 19, 2022
Several oral (asundexian, milvexian) and parenteral (abelacimab, osocimab, xisomab, IONIS-FXI, fesomersen) factor XIa inhibitors are under development...Non-anticoagulant drugs, such as colchicine, metformin and dronedarone, also being investigated to reduce the burden of NVAF and cardioembolic stroke. Additional clinical data are needed to more clearly define the role of these drugs for stroke prevention in NVAF.
- |||||||||| fesomersen (IONIS-FXI-LRx) / Ionis, Bayer, IONIS-FXIRx / Bayer
Clinical, PK/PD data, Journal: PK/PD modelling of FXI antisense oligonucleotides to bridge the dose-FXI activity relation from healthy volunteers to end-stage renal disease patients. (Pubmed Central) - Feb 1, 2022
FXI-LICA (BAY2976217) shares the same RNA sequence as IONIS-FXI but contains a GalNAc-conjugation that facilitates asialoglycoprotein receptor (ASGPR)-mediated uptake into hepatocytes...The model was then used to predict dose dependent steady-state FXI activity following repeat once-monthly doses of FXI-LICA in a virtual ESRD patient population. Under the assumption of similar ASGPR expression in ESRD patients and healthy volunteers, doses of 40mg, 80mg, and 120mg FXI-LICA are expected to cover the target range of clinical interest for steady-state FXI activity in the Phase 2b study of FXI-LICA in ESRD patients undergoing hemodialysis.
- |||||||||| Clinical, Journal: The Safety and Efficacy of Novel Agents Targeting Factors XI and XII in Early Phase Human Trials. (Pubmed Central) - Dec 20, 2019
Other benefits of some of these drugs include once-monthly dosing and safety in patients with renal or hepatic impairment, while others offer quickly metabolized parenteral options, thus providing more convenient and widely available anticoagulation options. Though still far from the marketplace, drugs targeting FXI and FXII have the potential to usher in a new era of anticoagulation therapy.
- |||||||||| Xarelto (rivaroxaban) / Bayer, J&J, aspirin / Generic Mfg., IONIS-FXIRx / Bayer
Journal: Antithrombotic Agents. (Pubmed Central) - Nov 21, 2019
The aims of this article are to review the results of recent trials aimed at enhancing the benefit-risk profile of antithrombotic therapy and explain how these findings are changing our approach to the management of arterial and venous thrombosis. Focusing on these 2 aspects of thrombosis management, this article discusses 4 advances: (1) the observation that in some indications, lowering the dose of some direct oral anticoagulants reduces the risk of bleeding without compromising efficacy, (2) the recognition that aspirin is not only effective for secondary prevention of atherothrombosis but also for prevention of venous thromboembolism, (3) the finding that dual pathway inhibition with the combination of low-dose rivaroxaban to attenuate thrombin generation plus aspirin to reduce thromboxane A2-mediated platelet activation is superior to aspirin or rivaroxaban alone for prevention of atherothrombosis in patients with coronary or peripheral artery disease, and (4) the development of inhibitors of factor XI or XII as potentially safer anticoagulants.
- |||||||||| IONIS-FXIRx / Bayer
Inhibition of Coagulation Factor XI Suppress Progression of Atherosclerosis (111AB) - Sep 20, 2019 - Abstract #AHA2019AHA_8438;
We administered saline (control), anti-FXI antibody that inhibits FXI activation by FXII (14E11; 4mg/kg), or GalNAc-conjugated FXI antisense oligonucleotide that reduces FXI synthesis (FXI-ASO; 7.5mg/kg) weekly to 8-week-old LDLR -/- mice fed a high-fat diet (HFD) for 8 weeks...Our data support a scenario whereby FXI activation induces structural changes in endothelial cells to increase their permeability. Increased endothelial permeability has been shown to enhance infiltration of cellular and acellular material into the artery wall, which can promote early plaque formation, and contribute to the pathogenesis of atherosclerosis.
|
