Recombinant factor VIIa analog in the management of hemophilia with inhibitors: Results from a multicenter, randomized, controlled trial of vatreptacog alfa

Journal of Thrombosis and Haemostasis

Volumn 12, Issue 8, 2014, Pages 1244-1253

  Lentz, S R ^a,g   Ehrenforth, S ^b   Abdul Karim, F ^c   Matsushita, T ^d   Weldingh, K N ^b   Windyga, J ^e   Mahlangu, J N ^f   Weltermann, A ^g   de Paula, E ^g   Cerqueira, M ^g   Zupancic Salek, S ^g   Katsarou, O ^g   Economou, M ^g   Nemes, L ^g   Boda, Z ^g   Santagostino E , ^g   Tagariello, G ^g   Hanabusa, H ^g   Fukutake, K ^g   Taki, M ^g   Shima, M ^g   Gorska Kosicka, M ^g   Serban, M ^g   Andreeva, T ^g   Savic, A ^g   Elezovic, I ^g   Mahlangu, J ^g   Tsay, W ^g   Shen, M ^g   Chuansumrit, A ^g   Angchaisuksiri, P ^g   Kavakli, K ^g   Kupesiz, A ^g   Sasmaz, I ^g   Madan, B ^g   Rangarajan, S ^g   Giangrande, P ^g   Saxena, K ^g   Recht, M ^g   Kempton, C ^g   Barrett, J ^g   Young, G ^g   Quon, D ^g   Stopeck, A ^g   Lin, J ^g   Ameri, A ^g   Kaicker, S ^g   Kuriakose, P ^g   Obzut, D ^g   Wang, M ^g   Ortiz, I ^g   Sori, A ^g   more..

^a UNIVERSITY OF IOWA   (United States)

^b NOVO NORDISK A S   (Denmark)

^c National Blood Centre   (Malaysia)

^d NAGOYA UNIVERSITY HOSPITAL   (Japan)

^e INSTITUTE OF HEMATOLOGY AND TRANSFUSION MEDICINE   (Poland)

^f UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^g NONE

Author keywords

Antibodies; Clinical trial, phase III; Hemophilia; Inhibitors; Recombinant factor VIIa

Indexed keywords

BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 9; DRUG ANTIBODY; RECOMBINANT BLOOD CLOTTING FACTOR 7A; BLOOD CLOTTING FACTOR 7A; RECOMBINANT PROTEIN;

AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; CROSS REACTION; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG ACTIVITY; DRUG EFFICACY; DRUG SAFETY; DRUG SCREENING; DRUG SURVEILLANCE PROGRAM; FEMALE; HEALTH CARE QUALITY; HEMOPHILIA A; HEMOPHILIA B; HUMAN; IMMUNOGENICITY; MAJOR CLINICAL STUDY; MULTICENTER STUDY; OUTCOME ASSESSMENT; PAIN ASSESSMENT; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RISK ASSESSMENT; SINGLE DRUG DOSE; THROMBOEMBOLISM; TREATMENT FAILURE; ADOLESCENT; ADULT; AGED; CHILD; CLINICAL TRIAL; MALE; MIDDLE AGED; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; CHILD; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; FACTOR VIIA; HEMOPHILIA A; HUMANS; MALE; MIDDLE AGED; RECOMBINANT PROTEINS; YOUNG ADULT;

EID: 84905669201     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12634     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. Kavakli K, Makris M, Zulfikar B, Erhardtsen E, Abrams ZS, Kenet G, NovoSeven trial (F7HAEM-1510) investigators. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Persson E, Olsen OH, Bjørn SE, Ezban M. Vatreptacog alfa from conception to clinical proof of concept. Semin Thromb Hemost 2012; 38: 274-81.
8. 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.
9. Brophy DF, Martin EJ, Nolte ME, Kuhn JG, Barrett J, 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.
10. ™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.
11. 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.
12. 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.
13. Yatuv R, Dayan I, Carmel-Goren L, Robinson M, Aviv I, Goldenberg-Furmanov M, Baru M. Enhancement of factor VIIa haemostatic efficacy by formulation with PEGylated liposomes. Haemophilia 2008; 14: 476-83.
14. Moss J, Rosholm A, Lauren A. Safety and pharmacokinetics of a glycoPEGylated recombinant activated factor VII derivative: a randomized first human dose trial in healthy subjects. J Thromb Haemost 2011; 9: 1368-74.
15. ™1 Investigators. 40K glycoPEGylated, recombinant FVIIa: 3-month, double-blind, randomized trial of safety, pharmacokinetics and preliminary efficacy in hemophilia patients with inhibitors. J Thromb Haemost 2013; 11: 1260-8.
16. Dickneite G, Zollner S, Weimer T, Schürmann D, Schmidbauer S, Raquet E, Mueller-Cohrs J, Pragst I, Schulte S. Prolonged serum half-life of a recombinant fusion protein linking activated coagulation factor VII with albumin (FVIIa-FP) in different preclinical species. J Thromb Haemost 2011; 9(Suppl. 2): 385.
17. Golor G, Bensen-Kennedy D, Haffner S, Easton R, Jung K, Moises T, Lawo J-P, Joch C, Veldman A. Safety and pharmacokinetics of a recombinant fusion protein linking coagulation factor VIIa with albumin in healthy volunteers. J Thromb Haemost 2013; 11: 1977-85.
18. Toso R, Bernardi F, Tidd T, Pinotti M, Camire RM, Marchetti G, High KA, Pollak ES. Factor VII mutant V154G models a zymogen-like form of factor VIIa. Biochem J 2003; 369: 563-71.
19. Sim DS, Koellnberger M, Gu JM, Bornaes C, Kragh M, Clausen SK, Murphy JE, Haaning J. BAY 86-6150, a novel recombinant factor VIIa variant, has a significantly higher therapeutic index than eptacog alfa (activated) in rabbit bleeding and thrombosis models. J Thromb Haemost 2011; 9(Suppl. 2): 297.
20. 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.
21. Schneiderman J, Rubin E, Nugent DJ, Young G. Sequential therapy with activated prothrombin complex concentrates and recombinant FVIIa in patients with severe haemophilia and inhibitors: update of our previous experience. Haemophilia 2007; 13: 244-8.
22. Abshire T, Kenet G. Safety update on the use of recombinant factor VIIa and the treatment of congenital and acquired deficiency of factor VIII or IX with inhibitors. Haemophilia 2008; 14: 898-902.
23. Salaj P, Ovesna P, Penka M, Hedner U. Analyses of recombinant activated factor VII treatments from clinical practice for rapid bleeding and acute pain control in haemophilia patients with inhibitors. Haemophilia 2012; 18: e409-11.
24. Chambost H, Santagostino E, Laffan M, Kavakli K, ONE Registry Steering Committee on behalf of the investigators. Real-world outcomes with recombinant factor VIIa treatment of acute bleeds in haemophilia patients with inhibitors: results from the international ONE registry. Haemophilia 2013; 19: 571-7.
25. Tamilvanan S, Raja NL, Sa B, Basu SK. Clinical concerns of immunogenicity produced at the cellular level by biopharmaceuticals following their parenteral administration in human body. J Drug Target 2010; 18: 489-98.
26. Sommer C, Norbert Jørgensen P, 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.
27. Møss J, Scharling B, Ezban M, Møller Sørensen T. 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.
28. Bayer Investor News: Bayer Provides Update on Phase II/III Trial of BAY 86-6150. BayerNews-20130503_0256. http://press.healthcare.bayer.com/en/press/news-details-page.php/15013/2013-0256. Accessed 25 June 2014.