Changes in the amino acid sequence of the recombinant human factor VIIa analog, vatreptacog alfa, are associated with clinical immunogenicity

Journal of Thrombosis and Haemostasis

Volumn 13, Issue 11, 2015, Pages 1989-1998

  Mahlangu, J N ^a   Weldingh, K N ^b   Lentz, S R ^c   Kaicker, S ^d   Karim, F A ^e   Matsushita, T ^f   Recht, M ^g   Tomczak, W ^h   Windyga, J ⁱ   Ehrenforth, S ^b   Knobe, K ^b   Weltermann, Ansgar ^j   de Paula, E ^j   Cerqueira, Monica ^j   Zupancic Salek, Silva ^j   Katsarou, Olga ^j   Economou, Marina ^j   Nemes, Laszlo ^j   Boda, Zoltan ^j   Santagostino, Elena ^j   Tagariello, Giuseppe ^j   Hanabusa, Hideji ^j   Fukutake, Katsuyuki ^j   Shima, Midori ^j   Serban, Margit ^j   Elezo vic, I ^j   Savic, Aleksandar ^j   Shen, Ming ^j   Chuansumrit, Ampaiwan ^j   Angchaisuksiri, Pantep ^j   Kavakli, Kaan ^j   Sasmaz, Ilgen ^j   Madan, Bella ^j   Giangrande, Paul ^j   Kempton, Christine ^j   Young, Guy ^j   Quon, Doris ^j   Ameri, Afshin ^j   Kuriakose, Philip ^j   Obzut, Dana ^j   Wang, Michael ^j   Ortiz, Idith ^j   more..

^a UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^b NOVO NORDISK A S   (Denmark)

^c UNIVERSITY OF IOWA   (United States)

^d MAIMONIDES MEDICAL CENTER   (United States)

^e National Blood Centre   (Malaysia)

^f NAGOYA UNIVERSITY HOSPITAL   (Japan)

^g OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^h MEDICAL UNIVERSITY OF LUBLIN   (Poland)

ⁱ INSTITUTE OF HEMATOLOGY AND TRANSFUSION MEDICINE   (Poland)

^j NONE   (United States)

more..

Author keywords

Antibodies; Antibody formation; Hemophilia; Immunoglobulin isotypes; Recombinant factor VIIa; Vatreptacog alfa

Indexed keywords

DRUG ANTIBODY; IMMUNOGLOBULIN G; RECOMBINANT BLOOD CLOTTING FACTOR 7A; ALLOANTIBODY; BLOOD CLOTTING FACTOR 7A; EPITOPE; HLA D ANTIGEN; RECOMBINANT PROTEIN;

ADOLESCENT; ADULT; AMINO ACID SEQUENCE; ANTIBODY PRODUCTION; ANTIBODY SPECIFICITY; ARTICLE; CLINICAL ARTICLE; CROSS REACTION; DRUG ELIMINATION; DRUG EXPOSURE; ENZYME LINKED IMMUNOSORBENT ASSAY; EPITOPE MAPPING; FOLLOW UP; HEMOPHILIA A; HEMOPHILIA B; HLA TYPING; HUMAN; IMMUNOGENICITY; IMMUNOGLOBULIN ISOTYPING; MALE; MULTICENTER STUDY (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POST HOC ANALYSIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SEROLOGY; AMINO ACID SUBSTITUTION; ANTIGEN ANTIBODY REACTION; BIOSYNTHESIS; BLOOD; CHEMISTRY; CLINICAL TRIAL; COMPARATIVE STUDY; CONTROLLED STUDY; GENETICS; HEMORRHAGE; IMMUNOLOGY; PHASE 3 CLINICAL TRIAL; PROTEIN TERTIARY STRUCTURE; RANDOMIZED CONTROLLED TRIAL; SERODIAGNOSIS; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANTIBODY SPECIFICITY; ANTIGEN-ANTIBODY REACTIONS; CROSS REACTIONS; EPITOPES; FACTOR VIIA; HEMOPHILIA A; HEMORRHAGE; HLA-D ANTIGENS; HUMANS; IMMUNOGLOBULIN G; ISOANTIBODIES; NEUTRALIZATION TESTS; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84946593161     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.13141     Document Type: Article

References (28)

1. Abshire T, Kenet G. Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost 2004; 2: 899-909.
2. Astermark J, Donfield SM, DiMichele DM, Gringeri A, Gilbert SA, Waters J, Berntorp E. A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study. Blood 2007; 109: 546-51.
3. Kavakli K, Makris M, Zulfikar B, Erhardtsen E, Abrams ZS, Kenet G. Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors. A multi-centre, randomised, double-blind, cross-over trial. Thromb Haemost 2006; 95: 600-5.
4. Parameswaran R, Shapiro AD, Gill JC, Kessler CM; HTRS Registry Investigators. Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Hemophilia and Thrombosis Research Society Registry. Haemophilia 2005; 11: 100-6.
5. Young G, Shafer FE, Rojas P, Seremetis S. Single 270 microg kg(-1)-dose rFVIIa vs. standard 90 microg kg(-1)-dose rFVIIa and APCC for home treatment of joint bleeds in haemophilia patients with inhibitors: a randomized comparison. Haemophilia 2008; 14: 287-94.
6. Mahlangu JN, Coetzee MJ, Laffan M, Windyga J, Yee TT, Schroeder J, Haaning J, Siegel JE, Lemm G. Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the recombinant factor VIIa variant BAY 86-6150 in hemophilia. J Thromb Haemost 2012; 10: 773-80.
7. Zollner S, Schuermann D, Raquet E, Mueller-Cohrs J, Weimer T, Pragst I, Dickneite G, Schulte S. Pharmacological characteristics of a novel, recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP). J Thromb Haemost 2014; 12: 220-8.
8. Persson E, Kjalke M, Olsen OH. Rational design of coagulation factor VIIa variants with substantially increased intrinsic activity. Proc Natl Acad Sci USA 2001; 98: 13583-8.
9. Ludlam CA, Smith MP, Morfini M, Gringeri A, Santagostino E, Savidge GF. A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation. Br J Haematol 2003; 120: 808-13.
10. Tiede A, Friedrich U, Stenmo C, Allen G, Giangrande P, Goudemand J, Hay C, Holmström M, Klamroth R, Lethagen S, McKenzie S, Miesbach W, Negrier C, Yuste VJ, Berntorp E. Safety and pharmacokinetics of subcutaneously administered recombinant activated factor VII (rFVIIa). J Thromb Haemost 2011; 9: 1191-9.
11. Brophy DF, Martin EJ, Nolte ME, Kuhn JG, Barrett JC, Ezban M. Factor VIIa analog has marked effects on platelet function and clot kinetics in blood from patients with hemophilia A. Blood Coagul Fibrinolysis 2010; 21: 539-46.
12. Ghosh S, Ezban M, Persson E, Pendurthi U, Hedner U, Rao LV. Activity and regulation of factor VIIa analogs with increased potency at the endothelial cell surface. J Thromb Haemost 2007; 5: 336-46.
13. Persson E, Olsen OH, Bjorn SE, Ezban M. Vatreptacog alfa from conception to clinical proof of concept. Semin Thromb Hemost 2012; 38: 274-81.
14. Sommer C, Norbert JP, Salanti Z, Clausen JT, Jensen LB. Immunogenicity of novel recombinant human activated factor VII analogues on factor VII neonatally-tolerized rats. Thromb Haemost 2007; 98: 721-5.
15. Møss J, Scharling B, Ezban M, Møller ST. Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects. J Thromb Haemost 2009; 7: 299-305.
16. ™1) Investigators. Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: a randomized controlled trial. J Thromb Haemost 2012; 10: 81-9.
17. Lentz SR, Ehrenforth S, Karim FA, Matsushita T, Weldingh KN, Windyga J, Mahlangu JN; adept™2 Investigators. Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa. J Thromb Haemost 2014; 12: 1244-53.
18. Sorensen BB, Persson E, Freskgârd PO, Kjalke M, Ezban M, Williams T, Rao LV. Incorporation of an active site inhibitor in factor VIIa alters the affinity for tissue factor. J Biol Chem 1997; 272: 11863-8.
19. Rand KD, Andersen MD, Olsen OH, Jørgensen TJ, Ostergaard H, Jensen ON, Stennicke HR, Persson E. The origins of enhanced activity in factor VIIa analogs and the interplay between key allosteric sites revealed by hydrogen exchange mass spectrometry. J Biol Chem 2008; 283: 13378-87.
20. de van Weert M, Horn Møller E, eds. Immunogenicity of Biopharmaceuticals. Copenhagen: Springer, 2008.
21. Shankar G, Pendley C, Stein KE. A risk-based bioanalytical strategy for the assessment of antibody immune responses against biological drugs. Nat Biotechnol 2007; 25: 555-61.
22. Whelan SF, Hofbauer CJ, Horling FM, Allacher P, Wolfsegger MJ, Oldenburg J, Male C, Windyga J, Tiede A, Schwarz HP, Scheiflinger F, Reipert BM. Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients. Blood 2013; 121: 1039-48.
23. Brinks V, Weinbuch D, Baker M, Dean Y, Stas P, Kostense S, Rup B, Jiskoot W. Preclinical models used for immunogenicity prediction of therapeutic proteins. Pharm Res 2013; 30: 1719-28.
24. Ponce R, Abad L, Amaravadi L, Gelzleichter T, Gore E, Green J, Gupta S, Herzyk D, Hurst C, Ivens IA, Kawabata T, Maier C, Mounho B, Rup B, Shankar G, Smith H, Thomas P, Wierda D. Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies. Regul Toxicol Pharmacol 2009; 54: 164-82.
25. Pavlova A, Delev D, Lacroix-Desmazes S, Schwaab R, Mende M, Fimmers R, Astermark J, Oldenburg J. Impact of polymorphisms of the major histocompatibility complex class II, interleukin-10, tumor necrosis factor-alpha and cytotoxic T-lymphocyte antigen-4 genes on inhibitor development in severe hemophilia A. J Thromb Haemost 2009; 7: 2006-15.
26. Schwarz J, Astermark J, Menius ED, Carrington M, Donfield SM, Gomperts ED, Nelson GW, Oldenburg J, Pavlova A, Shapiro AD, Winkler CA, Berntorp E. F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort. Haemophilia 2013; 19: 113-8.
27. Shepherd AJ, Skelton S, Sansom CE, Gomez K, Moss DS, Hart DP. A large-scale computational study of inhibitor risk in non-severe haemophilia A. Br J Haematol 2015; 168: 413-20.
28. Sauna ZE, Ameri A, Kim B, Yanover C, Viel KR, Rajalingam R, Cole SA, Howard TE. Observations regarding the immunogenicity of BDD-rFVIII derived from a mechanistic personalized medicine perspective. J Thromb Haemost 2012; 10: 1961-5.