433
Views
0
CrossRef citations to date
0
Altmetric
Review

A review of emerging factor XI inhibitors

, ORCID Icon &
Pages 43-53 | Received 22 Nov 2022, Accepted 15 Mar 2023, Published online: 21 Mar 2023

References

  • Raskob GE, Angchaisuksiri P, Blanco AN, et al. Thrombosis: a major contributor to global disease burden. Thromb Res. 2014;134(5):931–938.
  • Gale AJ. Current understanding of hemostasis. Toxicol Pathol. 2011;39:273.
  • Umerah CO, II M. Anticoagulation. decision-making in orthopedic and regional anesthesiology: a case-based approach [Internet]. 2022 [cited 2022 Aug 6];47–52. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560651/.
  • LaPelusa A, Dave HD. Physiology, Hemostasis. StatPearls [Internet]. 2022 [cited 2022 Aug 5]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK545263/.
  • Solari F, Varacallo M. Low molecular weight heparin (LMWH). StatPearls [Internet]. 2022 [cited 2022 Aug 6]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK525957/.
  • Levine M, Gresham C, Ruha A-M. Toxicology case files case files of the medical toxicology fellowship at banner good Samaritan Medical Center in phoenix, AZ: a non-warfarin anticoagulant overdose CASE PRESENTATION. J Med Toxical. 2009;5.
  • Baugh CW, Levine M, Cornutt D, et al. Anticoagulant reversal strategies in the emergency department setting: recommendations of a multidisciplinary expert panel. Ann Emerg Med. 2020;76:470–485.
  • Harter K, Levine M, Henderson S. Anticoagulation Drug Therapy: a Review. West J Emerg Med. 2015;16:11–17.
  • Georgi B, Mielke J, Chaffin M, et al. Leveraging human genetics to estimate clinical risk reductions achievable by inhibiting factor XI. Stroke. 2019;50:3004–3012.
  • Fredenburgh JC, Weitz JI. Factor XI as a target for new anticoagulants. Hamostaseologie. 2021;41:104–110.
  • Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke. 1991;22:983–988.
  • Farge D, Frere C, Connors JM, et al. international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol. 2022;2022(23):e334–e347.
  • Weitz JI, Haas S, Ageno W, et al. Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE. J Thromb Thrombolysis. 2020;50:267–277.
  • Cheung CYS, Parikh J, Farrell A, et al. Direct oral anticoagulant use in chronic kidney disease and dialysis patients with venous thromboembolism: a systematic review of thrombosis and bleeding outcomes. Ann Pharmacother. 2021;55:711–722.
  • Kuno T, Takagi H, Ando T, et al. Oral anticoagulation for patients with atrial fibrillation on long-term dialysis. J Am Coll Cardiol. 2020;75:273–285.
  • Székely O, Borgi M, Lip GYH. Factor XI inhibition fulfilling the optimal expectations for ideal anticoagulation. Expert Opin Emerg Drugs.2019;24(1):55–61.
  • Franchini M, Liumbruno GM, Bonfanti C, et al. The evolution of anticoagulant therapy. Blood Transfus. 2016;14:175–184.
  • Chen A, Stecker E, Warden B A. Direct oral anticoagulant use: a practical guide to common clinical challenges. J Am Heart Assoc. 2020;9(13): 1–18 .
  • Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev. 2003;17:S1–S5.
  • Ho KM, Pavey W. Applying the cell-based coagulation model in the management of critical bleeding. Anaesth Intensive Care. 2017;45:166–176.
  • Fredenburgh JC, Weitz JI. Factor XI as a target for new anticoagulants. hamostaseologie [Internet]. 2021 [cited 2022 Aug 9];41:104–110. Available from: https://pubmed.ncbi.nlm.nih.gov/33860518/.
  • Key NS. Epidemiologic and clinical data linking factors XI and XII to thrombosis. Hematology. 2014;2014:66–70.
  • Puy C, Rigg RA, McCarty OJT. The hemostatic role of factor XI. Thromb Res. 2016;141:S8–S11.
  • Bolton-Maggs PHB, Novel A. Assay for determining bleeding risk in factor XI deficiency. Thromb Haemost [Internet]. 2021 [cited 2022 Nov 13];121:121
  • Sharman Moser S, Chodick G, Ni YG, et al. The association between factor XI deficiency and the risk of bleeding, cardiovascular, and venous thromboembolic events. Thromb Haemost. 2022;122:808–817.
  • Zadra G, Asselta R, Tenchini ML, et al. Simultaneous genotyping of coagulation factor XI type II and type III mutations by multiplex real-time polymerase chain reaction to determine their prevalence in healthy and factor XI-deficient Italians. Haematologica. 2008;93:715–721.
  • Peyvandi F, Palla R, Menegatti M, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European network of rare bleeding disorders. J Thromb Haemost. 2012;10:615–621.
  • Wang X, Cheng Q, Xu L, et al. Effects of factor IX or factor XI deficiency on ferric chloride‐induced carotid artery occlusion in mice. J Thromb Haemost. 2005;3:695–702.
  • Weitz JI, Fredenburgh JC. Factors XI and XII as targets for new anticoagulants. Front Med (Lausanne). 2017;4:19.
  • Mullard A. FDA approves 100th monoclonal antibody product. Nat Rev Drug Discov. 2021;20:491–495.
  • Koch AW, Schiering N, Melkko S, et al. MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans. Blood. 2019;133:1507–1516.
  • Yi BA, Freedholm D, Widener N, et al. Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of factor XI and Factor XIa. J Thromb Haemost. 2022;20:307–315.
  • Verhamme P, Yi BA, Segers A, et al. Abelacimab for prevention of venous thromboembolism. N Engl J Med. 2021;385:609–617.
  • Thomas D, Thelen K, Kraff S, et al. BAY 1213790, a fully human IgG1 antibody targeting coagulation factor XIa: first evaluation of safety, pharmacodynamics, and pharmacokinetics. Res Pract Thromb Haemost. 2019;3:242–253.
  • Weitz JI, Bauersachs R, Becker B, et al. Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthroplasty: the FOXTROT randomized clinical trial. JAMA. 2020;323:130–139.
  • Nowotny B, Thomas D, Schwers S, et al. First randomized evaluation of safety, pharmacodynamics, and pharmacokinetics of BAY 1831865, an antibody targeting coagulation factor XI and factor XIa, in healthy men. J Thromb Haemost. 2022;20:1684–1695.
  • Lorentz CU, Verbout NG, Wallisch M, et al. Contact activation inhibitor and factor XI antibody, AB023, produces safe, dose-dependent anticoagulation in a phase 1 first-in-human trial. Arterioscler Thromb Vasc Biol. 2019;39:799–809.
  • Lorentz CU, Tucker EI, Verbout NG, et al. The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial. Blood. 2021;138:2173–2184.
  • Thomas D, Kanefendt F, Schwers S, et al. First evaluation of the safety, pharmacokinetics, and pharmacodynamics of BAY 2433334, a small molecule targeting coagulation factor XIa. J Thromb Haemost. 2021;19:2407–2416.
  • Piccini JP, Caso V, Connolly SJ, et al. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. Lancet. 2022;399:1383–1390.
  • Rao SV, Kirsch B, DL B, et al. A multicenter, phase 2, randomized, placebo-controlled, double-blind, parallel-group, dose-finding trial of the oral factor xia inhibitor asundexian to prevent adverse cardiovascular outcomes after acute myocardial infarction. Circulation. 2022;146:1196–1206.
  • Shoamanesh A, Mundl H, Smith EE, et al. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022;400:997–1007.
  • Perera V, Wang Z, Luettgen J, et al. First‐in‐human study of milvexian, an oral, direct, small molecule factor XIa inhibitor. Clin Transl Sci. 2022;15:330–342.
  • Perera V, Abelian G, Li D, et al. Single-dose pharmacokinetics of milvexian in participants with mild or moderate hepatic impairment compared with healthy participants. Clin Pharmacokinet. 2022;61:857–867.
  • Perera V, Wang Z, Lubin S, et al. Effects of itraconazole and diltiazem on the pharmacokinetics and pharmacodynamics of milvexian, a factor xia inhibitor. Cardiol Ther. 2022;11:407–419.
  • Weitz JI, Strony J, Ageno W, et al. Milvexian for the prevention of venous thromboembolism. N Engl J Med. 2021;385:2161–2172.
  • Kumbhani DJ. Antithrombotic treatment with factor xia inhibition to optimize management of acute thromboembolic events for secondary stroke prevention - AXIOMATIC-SSP [Internet]. [cited 2022 Nov 2]. Available from: https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2022/08/27/04/12/AXIOMATIC-SSP.
  • Crooke ST, Liang X-H, Baker BF, et al. Antisense technology: a review. J Biol Chem. 2021;296:100416.
  • Liu Q, Bethune C, Dessouki E, et al. ISIS-FXIRx, A novel and specific antisense inhibitor of factor XI, caused significant reduction in FXI antigen and activity and increased aPTT without causing bleeding in healthy volunteers. Blood. 2011;118: 209–209.
  • Büller HR, Bethune C, Bhanot S, et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015;372:232–240.
  • Walsh M, Bethune C, Smyth A, et al. Phase 2 study of the factor XI antisense inhibitor IONIS-FXIRx in patients with ESRD. Kidney Int Rep. 2022;7:200–209.
  • Willmann S, Marostica E, Snelder N, et al. PK/PD modeling of FXI antisense oligonucleotides to bridge the dose‐FXI activity relation from healthy volunteers to end‐stage renal disease patients. CPT Pharmacometrics Syst Pharmacol. 2021;10:890–901.
  • Pharmaceuticals I. Ionis announces positive topline results from Phase 2b clinical study of fesomersen, a potential novel anti-thrombotic treatment [Internet]. [cited 2023 Feb 12]. Available from: https://www.prnewswire.com/news-releases/ionis-announces-positive-topline-results-from-phase-2b-clinical-study-of-fesomersen-a-potential-novel-anti-thrombotic-treatment-301594902.html.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.