- |||||||||| Review, Journal: From the INVICTUS Trial to Current Considerations: It's Not Time to Retire Vitamin K Inhibitors Yet! (Pubmed Central) - Nov 27, 2024
In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death...Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility...Multiple agents (monoclonal antibodies-e.g., osocimab, anti-sense oligonucleotides-e.g., fesomersen, and small molecule inhibitors-e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.
- |||||||||| fesomersen (IONIS-FXI-LRx) / Ionis
Journal: Factor XI inhibition in hemodialysis patients: the safer anticoagulation? (Pubmed Central) - Jun 22, 2024
Factor XI inhibition may provide anticoagulation, with a low risk of bleeding, and several factor XI inhibitors, including fesomersen, an antisense oligonucleotide, are under development. Recently, a phase 2 study of fesomersen showed a good safety profile in chronic hemodialysis patients and suggested that clotting rates of the arteriovenous fistula and the dialysis circuit are lower.
- |||||||||| 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.).
- |||||||||| fesomersen (IONIS-FXI-LRx) / Ionis
PK/PD data, Journal: Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers. (Pubmed Central) - Apr 6, 2024
The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants.
- |||||||||| 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.
- |||||||||| 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.
- |||||||||| 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.
- |||||||||| fesomersen (IONIS-FXI-LRx) / Ionis
Enrollment closed: RE-THINc ESRD: Factor XI LICA to Reduce Events Such as Heart Attack and Stroke in Patients Whose Kidneys Are no Longer Able to Work as They Should and Require Treatment to Filter Wastes From the Blood: Focus is on the Safety of BAY2976217 and the Way the Body Absorbs, Distributes and Removes the Study Drug (clinicaltrials.gov) - Aug 4, 2021
P2, N=305, Active, not recruiting,
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. Recruiting --> Active, not recruiting
- |||||||||| fesomersen (IONIS-FXI-LRx) / Ionis
Enrollment closed: A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of IONIS FXI-LRx in up to 84 Healthy Volunteers (clinicaltrials.gov) - Jan 9, 2019
P1, N=66, Active, not recruiting,
Active, not recruiting --> Completed Recruiting --> Active, not recruiting
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