A bispecific antibody demonstrates limited measurability in routine coagulation assays.
Journal
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
ISSN: 1473-5733
Titre abrégé: Blood Coagul Fibrinolysis
Pays: England
ID NLM: 9102551
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
30
5
2020
medline:
7
4
2021
entrez:
30
5
2020
Statut:
ppublish
Résumé
: Accurate monitoring of coagulation, needed for optimal management of patients with haemophilia A with inhibitors, presents a challenge for treating physicians. Although global haemostatic assays may be used in this population, their utility with nonfactor therapies has yet to be established in the clinical setting. The aim of this study was to assess options for potential haemostatic activity monitoring and feasibility for factor VIII (FVIII)-equivalency measurement with a sequence identical analogue (SIA) to emicizumab using different coagulation assays. SIA was analysed using five commercial chromogenic assays and activated partial thromboplastin time (aPTT) assays including clot waveform analysis using five different triggers. Recombinant FVIII served as a comparator in all assays. Thrombin generation in haemophilia A plasma was measured using extrinsic and intrinsic trigger conditions (tissue factor or Factor XIa). Of the five chromogenic assays, a concentration-dependent increase in Factor Xa was observed with one assay, with human Factor IXa and X reagents. The SIA dose-response signal plateaued at therapeutically relevant concentrations and was nonparallel with FVIII reference, thereby not permitting FVIII-equivalence assessment. aPTT varied between reagents, with aPTT normalization occurring at low and below-therapeutic SIA concentrations. SIA [600 nmol/l (90 μg/ml)] only partially restored thrombin generation in individual haemophilia A patient plasma. FVIII-equivalence of SIA could not be determined using standard FVIII protocols and was found to be highly influenced by assay type, analytical conditions and parameters used for calculation. New and/or modified methodology and standard reagents specific for use with nonfactor therapies are required for their utilization in the clinical setting.
Identifiants
pubmed: 32467424
doi: 10.1097/MBC.0000000000000921
pii: 00001721-202008000-00003
doi:
Substances chimiques
Antibodies, Bispecific
0
Antibodies, Monoclonal, Humanized
0
emicizumab
7NL2E3F6K3
F8 protein, human
839MOZ74GK
Factor VIII
9001-27-8
Factor X
9001-29-0
Factor Xa
EC 3.4.21.6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-365Références
Hoyer LW. Hemophilia A. N Engl J Med 1994; 330:38–47.
Coppola A, Di Capua M, Di Minno MN, Di Palo M, Marrone E, Ierano P, et al. Treatment of hemophilia: a review of current advances and ongoing issues. J Blood Med 2010; 1:183–195.
van Dijk K, van der Bom JG, Lenting PJ, de Groot PG, Mauser-Bunschoten EP, Roosendaal G, et al. Factor VIII half-life and clinical phenotype of severe hemophilia A. Haematologica 2005; 90:494–498.
Tiede A. Half-life extended factor VIII for the treatment of hemophilia A. J Thromb Haemost 2015; 13: (Suppl 1): S176–S179.
Powell JS. Longer-acting clotting factor concentrates for hemophilia. J Thromb Haemost 2015; 13: (Suppl 1): S167–S175.
Baxalta US Inc. ADYNOVATE, Antihemophilic factor (Recombinant), PEGylated lyophilized powder for solution for intravenous injection prescribing information. 2017. http://www.shirecontent.com/PI/PDFs/ADYNOVATE_USA_ENG.pdf. [Accessed 21 September 2017].
Bayer Healthcare LLC. KOVALTRY [Antihemophilic Factor (Recombinant)] lyophilized powder for solution for intravenous injection prescribing information. 2016. Available at: http://labeling.bayerhealthcare.com/html/products/pi/Kovaltry_PI.pdf. [Accessed 21 Sep 2017].
Bioverativ Therapeutics Inc. ELOCTATE [Antihemophilic Factor (Recombinant), Fc Fusion Protein] lyophilized powder for solution for intravenous injection prescribing information. 2017. https://www.eloctate.com/Pdfs/full-prescribing-information.pdf. [Accessed 21 Sep 2017].
Ewing N, Escuriola-Ettingshausen C, Kreuz W. Prophylaxis with FEIBA in paediatric patients with haemophilia A and inhibitors. Haemophilia 2015; 21:358–364.
Ju HY, Jang HL, Park YS. The efficacy of bypassing agents in surgery of hemophilia patients with inhibitors. Blood Res 2015; 50:173–178.
Hilden I, Lauritzen B, Sorensen BB, Clausen JT, Jespersgaard C, Krogh BO, et al. Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model. Blood 2012; 119:5871–5878.
Cardinal M, Kantaridis C, Zhu T, Sun P, Pittman DD, Murphy JE, et al. A first-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-06741086, an antitissue factor pathway inhibitor mAb, in healthy volunteers. J Thromb Haemost 2018; 16:1722–1731.
Gu JM, Zhao XY, Schwarz T, Schuhmacher J, Baumann A, Ho E, et al. Mechanistic modeling of the pharmacodynamic and pharmacokinetic relationship of tissue factor pathway inhibitor-neutralizing antibody (BAY 1093884) in cynomolgus monkeys. AAPS J 2017; 19:1186–1195.
Waters EK, Genga RM, Schwartz MC, Nelson JA, Schaub RG, Olson KA, et al. Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhibitor. Blood 2011; 117:5514–5522.
Waters EK, Genga RM, Thomson HA, Kurz JC, Schaub RG, Scheiflinger F, et al. Aptamer BAX 499 mediates inhibition of tissue factor pathway inhibitor via interaction with multiple domains of the protein. J Thromb Haemost 2013; 11:1137–1145.
Dockal M, Hartmann R, Fries M, Thomassen MC, Heinzmann A, Ehrlich H, et al. Small peptides blocking inhibition of factor Xa and tissue factor-factor VIIa by tissue factor pathway inhibitor (TFPI). J Biol Chem 2014; 289:1732–1741.
Sehgal A, Barros S, Ivanciu L, Cooley B, Qin J, Racie T, et al. An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia. Nat Med 2015; 21:492–497.
Genetech Inc. Hemlibra prescribing information. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761083s002s004lbl.pdf. [Accessed 10 May 2019].
Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med 2016; 374:2044–2053.
Nogami K. A bispecific antibody mimicking factor VIII in hemophilia A therapy. Rinsho Ketsueki 2016; 57:709–714.
Nogami K. Bispecific antibody mimicking factor VIII. Thromb Res 2016; 141: (Suppl 2): S34–S35.
Kitazawa T, Esaki K, Tachibana T, Ishii S, Soeda T, Muto A, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost 2017; 117:1348–1357.
Muto A, Yoshihashi K, Takeda M, Kitazawa T, Soeda T, Igawa T, et al. Antifactor IXa/X bispecific antibody ACE910 prevents joint bleeds in a long-term primate model of acquired hemophilia A. Blood 2014; 124:3165–3171.
Uchida N, Sambe T, Yoneyama K, Fukazawa N, Kawanishi T, Kobayashi S, et al. A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood 2016; 127:1633–1641.
Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med 2018; 379:811–822.
Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med 2017; 377:809–818.
Lenting PJ, Denis CV, Christophe OD. Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII? Blood 2017; 130:2463–2468.
White GC 2nd, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001; 85:560.
Viuff D, Barrowcliffe T, Saugstrup T, Ezban M, Lillicrap D. International comparative field study of N8 evaluating factor VIII assay performance. Haemophilia 2011; 17:695–702.
Trossaert M, Regnault V, Sigaud M, Boisseau P, Fressinaud E, Lecompte T. Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype. J Thromb Haemost 2008; 6:486–493.
Rodgers S, Duncan E. Chromogenic factor VIII assays for improved diagnosis of hemophilia A. Methods Mol Biol 2017; 1646:265–276.
Pickering W, Hansen M, Kjalke M, Ezban M. Factor VIII chromogenic assays can be used for potency labeling and postadministration monitoring of N8-GP. J Thromb Haemost 2016; 14:1579–1587.
Turecek PL, Romeder-Finger S, Apostol C, Bauer A, Crocker-Buque A, Burger DA, et al. A world-wide survey and field study in clinical haemostasis laboratories to evaluate FVIII:C activity assay variability of ADYNOVATE and OBIZUR in comparison with ADVATE. Haemophilia 2016; 22:957–965.
Kitchen S, Kershaw G, Tiefenbacher S. Recombinant to modified factor VIII and factor IX: chromogenic and one-stage assays issues. Haemophilia 2016; 22: (Suppl 5): 72–77.
Kenet G, Stenmo CB, Blemings A, Wegert W, Goudemand J, Krause M, et al. Intra-patient variability of thromboelastographic parameters following in vivo and ex vivo administration of recombinant activated factor VII in haemophilia patients. A multicentre, randomised trial. Thromb Haemost 2010; 103:351–359.
Sommer JM, Buyue Y, Bardan S, Peters RT, Jiang H, Kamphaus GD, et al. Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity. Thromb Haemost 2014; 112:932–940.
Shima M, Thachil J, Nair SC, Srivastava A, Scientific and Standardization Committee. Towards standardization of clot waveform analysis and recommendations for its clinical applications. J Thromb Haemost 2013; 11:1417–1420.
Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysio Haemost Thromb 2003; 33:4–15.
Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, et al. Targeting of antithrombin in hemophilia A or B with RNAi therapy. N Engl J Med 2017; 377:819–828.
Chowdary P, Lethagen S, Friedrich U, Brand B, Hay C, Abdul Karim F, et al. Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial. J Thromb Haemost 2015; 13:743–754.
National Hemophilia Association. MASAC update on the approval and availability of the new treatment. 2018. https://www.hemophilia.org/Newsroom/Medical-News/MASAC-Safety-Information-Update-on-Emicizumab-HEMLIBRA. [Accessed 10 May 2019].
Matsumoto T, Nogami K, Tabuchi Y, Yada K, Ogiwara K, Kurono H, et al. Clot waveform analysis using CS-2000i distinguishes between very low and absent levels of factor VIII activity in patients with severe haemophilia A. Haemophilia 2017; 23:e427–e435.
van Veen JJ, Gatt A, Bowyer AE, Cooper PC, Kitchen S, Makris M. Calibrated automated thrombin generation and modified thromboelastometry in haemophilia A. Thromb Res 2009; 123:895–901.
Young G, Sorensen B, Dargaud Y, Negrier C, Brummel-Ziedins K, Key NS. Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives. Blood 2013; 121:1944–1950.
Adamkewicz JI, Chen DC, Paz-Priel I. Effects and interferences of emicizumab, a humanised bispecific antibody mimicking activated factor VIII cofactor function, on coagulation assays. Thromb Haemost 2019; 119:1084–1093.
Peyvandi F, Oldenburg J, Friedman KD. A critical appraisal of one-stage and chromogenic assays of factor VIII activity. J Thromb Haemost 2016; 14:248–261.