Longer-acting clotting factor concentrates for hemophilia

Journal of Thrombosis and Haemostasis

Volumn 13, Issue S1, 2015, Pages S167-S175

  Powell, J S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Blood coagulation factors; Factor IX; Factor VIIa; Factor VIII; Pharmacokinetics; Prophylaxis

Indexed keywords

ACE 910; BLOOD CLOTTING FACTOR; N9 GP; RECOMBINANT BLOOD CLOTTING FACTOR 7A; RECOMBINANT BLOOD CLOTTING FACTOR 8; RECOMBINANT BLOOD CLOTTING FACTOR 8 FC FUSION PROTEIN; RECOMBINANT BLOOD CLOTTING FACTOR 9; RECOMBINANT PROTEIN; TISSUE FACTOR PATHWAY INHIBITOR; UNCLASSIFIED DRUG; HEMOSTATIC AGENT; HYBRID PROTEIN; NEW DRUG;

BLOOD CLOTTING; CHEMICAL MODIFICATION; CLINICAL STUDY; DIAPHORESIS; DRUG ACTIVITY; DRUG APPROVAL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; FACE DISORDER; HEMOPHILIA; HEMOPHILIA B; HUMAN; MEDICATION COMPLIANCE; MULTICENTER STUDY (TOPIC); NAUSEA; NONHUMAN; PARESTHESIA; PEGYLATION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROPHYLAXIS; PROTEIN DOMAIN; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SWEAT GLAND DISEASE; SWELLING; VOMITING; ANIMAL; BLOOD; DRUG DEVELOPMENT; DRUG EFFECTS; HEMOPHILIA A; HEMORRHAGE; HEMOSTASIS; TREATMENT OUTCOME;

ANIMALS; BLOOD COAGULATION FACTORS; DRUG DISCOVERY; DRUGS, INVESTIGATIONAL; HEMOPHILIA A; HEMORRHAGE; HEMOSTASIS; HEMOSTATICS; HUMANS; RECOMBINANT FUSION PROTEINS; TREATMENT OUTCOME;

EID: 84931308974     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.12912     Document Type: Review

References (69)

1. Powell JS, Rogers GM. Inherited coagulation disorders. In: Greer JP, Arber DA, Glader B, List AF, Means RT, Paraskevas F, Rodgers GM, Foerster J, eds. Wintrobe's Clinical Hematology. Phildelphia, PA: Lippincott Williams & Wilkins, 2014: 1143-85.
2. Giangrande P. Haemophilia B: Christmas disease. Expert Opin Pharmacother 2005; 6: 1517-24.
3. Mannucci PM, Mendolicchio L, Gringeri A. Use of prophylaxis to prevent complications of hemophilia. Adv Exp Med Biol 2001; 489: 59-64.
4. Nilsson IM, Berntorp E, Lofqvist T, Pettersson H. Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 1992; 232: 25-32.
5. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, Ingram JD, Manco-Johnson ML, Funk S, Jacobson L, Valentino LA, Hoots WK, Buchanan GR, DiMichele D, Recht M, Brown D, Leissinger C, Bleak S, Cohen A, Mathew P, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357: 535-44.
6. Darby SC, Kan SW, Spooner RJ, Giangrande PL, Hill FG, Hay CR, Lee CA, Ludlam CA, Williams M. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood 2007; 110: 815-25.
7. White GC 2nd, Courter S, Bray GL, Lee M, Gomperts ED. A multicenter study of recombinant factor VIII (Recombinate) in previously treated patients with hemophilia A. The Recombinate Previously Treated Patient Study Group. Thromb Haemost 1997; 77: 660-7.
8. Feldman BM, Pai M, Rivard GE, Israels S, Poon MC, Demers C, Robinson S, Luke KH, Wu JK, Gill K, Lillicrap D, Babyn P, McLimont M, Blanchette VS. Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study. J Thromb Haemost 2006; 4: 1228-36.
9. Hacker MR, Geraghty S, Manco-Johnson MJ. Barriers to compliance with prophylaxis therapy in haemophilia. Haemophilia 2001; 7: 392-6.
10. Manco-Johnson MJ, Riske B, Kasper CK. Advances in care of children with hemophilia. Semin Thromb Haemost 2003; 29: 585-94.
11. Gater A, Thomson TA, Strandberg-Larsen M. Haemophilia B: impact on patients and economic burden of disease. Thromb Haemost 2011; 106: 398-404.
12. Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Della Peruta M, Lheriteau E, Patel N, Raj D, Riddell A, Pie J, Rangarajan S, Bevan D, Recht M, Shen YM, Halka KG, Basner-Tschakarjan E, Mingozzi F, High KA, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 2014; 371: 1994-2004.
13. Collins PW, Young G, Knobe K, Karim FA, Angchaisuksiri P, Banner C, Gürsel T, Mahlangu J, Matsushita T, Mauser-Bunschoten EP, Oldenburg J, Walsh CE, Negrier C, paradigm 2 Investigators. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood 2014; 124: 3880-6.
14. Martinowitz U, Shapiro A, Quon DV, Escobar M, Kempton C, Collins PW, Chowdary P, Makris M, Mannucci PM, Morfini M, Valentino LA, Gomperts E, Lee M. Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis. Haemophilia 2012; 18: 881-7.
15. Shapiro AD, Ragni MV, Valentino LA, Key NS, Josephson NC, Powell JS, Cheng G, Thompson AR, Goyal J, Tubridy KL, Peters RT, Dumont JA, Euwart D, Li L, Hallén B, Gozzi P, Bitonti AJ, Jiang H, Luk A, Pierce GF. Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. Blood 2012; 119: 666-72.
16. Metzner HJ, Pipe SW, Weimer T, Schulte S. Extending the pharmacokinetic half-life of coagulation factors by fusion to recombinant albumin. Thromb Haemost 2013; 110: 931-9.
17. Peters RT, Low SC, Kamphaus GD, Dumont JA, Amari JV, Lu Q, Zarbis-Papastoitsis G, Reidy TJ, Merricks EP, Nichols TC, Bitonti AJ. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood 2010; 115: 2057-64.
18. Santagostino E, Negrier C, Klamroth R, Tiede A, Pabinger-Fasching I, Voigt C, Jacobs I, Morfini M. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood 2012; 120: 2405-11.
19. Schmidt SR. Fusion-proteins as biopharmaceuticals-applications and challenges. Curr Opin Drug Discov Devel 2009; 12: 284-95.
20. Huang C. Receptor-Fc fusion therapeutics, traps, and MIMETIBODY technology. Curr Opin Biotechnol 2009; 20: 692-9.
21. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007; 7: 715-25.
22. Rath T, Baker K, Dumont JA, Peters RT, Jiang H, Qiao SW, Lencer WI, Pierce GF, Blumberg RS. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol 2013; 1-20.
23. Kontermann RE. Strategies for extended serum half-life of protein therapeutics. Curr Opin Biotechnol 2011; 22: 868-76.
24. Lusson J, Vieau D, Hamelin J, Day R, Chrétien M, Seidah NG. cDNA structure of the mouse and rat subtilisin/kexin-like PC5: a candidate proprotein convertase expressed in endocrine and nonendocrine cells. Proc Natl Acad Sci USA 1993; 90: 6691-5.
25. Powell JS, Pasi KJ, Ragni MV, Ozelo MC, Valentino LA, Mahlangu JN, Josephson NC, Perry D, Manco-Johnson MJ, Apte S, Baker RI, Chan GC, Novitzky N, Wong RS, Krassova S, Allen G, Jiang H, Innes A, Li S, Cristiano LM, et al. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med 2013; 369: 2313-23.
26. Lambert T, Recht M, Valentino LA, Powell JS, Udata C, Sullivan ST, Roth DA. Reformulated BeneFix: efficacy and safety in previously treated patients with moderately severe to severe haemophilia B. Haemophilia 2007; 13: 233-43 Erratum in: Haemophilia 2007; 13:450.
27. Roth DA, Kessler CM, Pasi KJ, Rup B, Courter SG, Tubridy KL, Recombinant Factor IX Study Group. Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood 2001; 98: 3600-6.
28. Powell JS, Josephson NC, Quon D, Ragni MV, Cheng G, Li E, Jiang H, Li L, Dumont JA, Goyal J, Zhang X, Sommer J, McCue J, Barbetti M, Luk A, Pierce GF. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood 2012; 119: 3031-7.
29. Mahlangu J, Powell JS, Ragni MV, Chowdary P, Josephson NC, Pabinger I, Hanabusa H, Gupta N, Kulkarni R, Fogarty P, Perry D, Shapiro A, Pasi KJ, Apte S, Nestorov I, Jiang H, Li S, Neelakantan S, Cristiano LM, Goyal J, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood 2014; 123: 317-25.
30. Shapiro AD, Ragni MV, Kulkarni R, Oldenberg J, Srivastava A, Quon DV, Pasi KJ, Hanabusa H, Pabinger I, Mahlangu J, Fogarty P, Lillicrap D, Kulke S, Potts J, Neelakantan S, Nestorov I, Li S, Dumont JA, Jiang H, Brennan A, et al. Recombinant factor VIII Fc fusion protein: extended-interval dosing maintains low bleeding rates and correlates with von Willebrand factor levels. J Thromb Haemost 2014; 12: 1788-800.
31. Sommer JM, Moore N, McGuffie-Valentine B, Bardan S, Buyue Y, Kamphaus GD, Konkle BA, Pierce GF. Comparative field study evaluating the activity of recombinant factor VIII Fc fusion protein in plasma samples at clinical haemostasis laboratories. Haemophilia 2014; 20: 294-300.
32. Kisker CT, Eisberg A, Schwartz B, Mononine Study Group. Prophylaxis in factor IX deficiency product and patient variation. Haemophilia 2003; 9: 279-84.
33. Bjorkman S. Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective. Haemophilia 2003; 9: 101-8 discussion 109-10.
34. Ahnström J, Berntorp E, Lindvall K, Björkman S. A 6-year follow-up of dosing, coagulation factor levels and bleedings in relation to joint status in the prophylactic treatment of haemophilia. Haemophilia 2004; 10: 689-97.
35. Weimer T, Wormsbächer W, Kronthaler U, Lang W, Liebing U, Schulte S. Prolonged in-vivo half-life of factor VIIa by fusion to albumin. Thromb Haemost 2008; 99: 659-67.
36. Schulte S. Innovative coagulation factors: albumin fusion technology and recombinant single-chain factor VIII. Thromb Res 2013; 131: S2-6.
37. Santagostino E. PROLONG-9FP clinical development program-phase I results of recombinant fusion protein linking coagulation factor IX with recombinant albumin (rIX-FP). Thromb Res 2013; 131: S7-10.
38. Gui T, Lin HF, Jin DY, Hoffman M, Straight D, Roberts HR, Darrel W, Stafford DW. Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo. Blood 2002; 100: 153-8.
39. Abuchowski A, van Es T, Palczuk NC, Davis FF. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem 1977; 252: 3578-81.
40. Caliceti P, Veronese FM. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 2003; 55: 1261-77.
41. Shen BW, Spiegel PC, Chang CH, Huh JW, Lee JS, Kim J, Kim YH, Stoddard BL. The tertiary structure and domain organization of coagulation factor VIII. Blood 2008; 111: 1240-7.
42. Ngo JC, Huang M, Roth DA, Furie BC, Furie B. Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex. Structure 2008; 16: 597-606.
43. Mei B, Pan C, Jiang H, Tjandra H, Strauss J, Chen Y, Liu T, Zhang X, Severs J, Newgren J, Chen J, Gu JM, Subramanyam B, Fournel MA, Pierce GF, Murphy JE. Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment. Blood 2010; 116: 270-9.
44. Horton S, Walsh C, Emery P. Certolizumab pegol for the treatment of rheumatoid arthritis. Expert Opin Biol Ther 2012; 12: 235-49.
45. Alconcel SNS, Baas AS, Maynard HD. FDA-approved poly(ethylene glycol)-protein conjugate drugs. Polym Chem 2011; 2: 1442-8.
46. Ivens IA, Baumann A, McDonald TA, Humphries TJ, Michaels LA, Mathew P. PEGylated therapeutic proteins for haemophilia treatment: a review for haemophilia caregivers. Haemophilia 2013; 19: 11-20.
47. Tang L, Leong L, Sim D, Ho E, Gu JM, Schneider D, Feldman RI, Monteclaro F, Jiang H, Murphy JE. von Willebrand factor contributes to longer half-life of PEGylated factor VIII in vivo. Haemophilia 2013; 19: 539-45.
48. Turecek PL, Bossard MJ, Graninger M, Gritsch H, Höllriegl W, Kaliwoda M, Matthiessen P, Mitterer A, Muchitsch EM, Purtscher M, Rottensteiner H, Schiviz A, Schrenk G, Siekmann J, Varadi K, Riley T, Ehrlich HJ, Schwarz HP, Scheiflinger F. BAX, 855, a PEGylated rFVIII product with prolonged half-life. Development, functional and structural characterisation. Hamostaseologie 2012; 32: S29-38.
49. Tiede A, Brand B, Fischer R, Kavakli K, Lentz SR, Matsushita T, Rea C, Knobe K, Viuff D. Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A. J Thromb Haemost 2013; 11: 670-8.
50. Sandberg H, Kannicht C, Stenlund P, Dadaian M, Oswaldsson U, Cordula C, Walter O. Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII. Thromb Res 2012; 130: 808-17.
51. Kannicht C, Ramstrom M, Kohla G, Tiemeyer M, Casademunt E, Walter O, Sandberg H. Characterisation of the post-translational modifications of a novel, human cell line-derived recombinant human factor VIII. Thromb Res 2013; 131: 78-88.
52. Schulte S. Challenges for new haemophilia products from a manufacturer's perspective. Thromb Res 2014; 134: S72-6.
53. Zollner SB, Raquet E, Müller-Cohrs J, Metzner HJ, Weimer T, Pragst I, Dickneite G, Schulte S. Preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII. Thromb Res 2013; 132: 280-7.
54. 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.
55. Kitazawa T, Igawa T, Sampei Z, Muto A, Kojima T, Soeda T, Yoshihashi K, Okuyama-Nishida Y, Saito H, Tsunoda H, Suzuki T, Adachi H, Miyazaki T, Ishii S, Kamata-Sakurai M, Iida T, Harada A, Esaki K, Funaki M, Moriyama C, et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med 2012; 18: 1570-4.
56. Muto A, Yoshihashi K, Takeda M, Kitazawa T, Soeda T, Igawa T, Sakamoto Y, Haraya K, Kawabe Y, Shima M, Yoshioka A, Hattori K. Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation. J Thromb Haemost 2014; 2: 206-13.
57. Shima M, Hermans C, de Moerloose P. Novel products for haemostasis. Haemophilia 2014; 20: 29-35.
58. Hilden I, Lauritzen B, Sørensen BB, Clausen JT, Jespersgaard C, Krogh BO, Bowler AN, Breinholt J, Gruhler A, Svensson LA, Petersen HH, Petersen LC, Balling KW, Hansen L, Hermit MB, Egebjerg T, Friederichsen B, Ezban M, Bjørn SE. Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model. Blood 2012; 119: 5871-8.
59. Agersø H, Overgaard RV, Petersen MB, Hansen L, Hermit MB, Sørensen MH, Petersen LC, Hilden I. Pharmacokinetics of an anti-TFPI monoclonal antibody (concizumab) blocking the TFPI interaction with the active site of FXa in Cynomolgus monkeys after iv and sc administration. Eur J Pharm Sci 2014; 56: 65-9.
60. Gorczyca ME, Nair SC, Jilma B, Priya S, Male C, Reitter S, Knoebl P, Gilbert JC, Schaub RG, Dockal M, McGinness KE, Pabinger I, Srivastava A. Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves clotting of hemophilic blood and plasma. J Thromb Haemost 2012; 10: 1581-90.
61. Prasad S, Lillicrap D, Labelle A, Knappe S, Keller T, Burnett E, Powell S, Johnson KW. Efficacy and safety of a new-class hemostatic drug candidate, AV513, in dogs with hemophilia A. Blood 2008; 111: 672-9.
62. Knappe S, Gorczyca ME, Jilma B, Derhaschnig U, Hartmann R, Palige M, Scheiflinger F, Dockal M. Plasmatic tissue factor pathway inhibitor is a major determinant of clotting in factor VIII inhibited plasma or blood. Thromb Haemost 2013; 109: 450-7.
63. Peraramelli S, Thomassen S, Heinzmann A, Rosing J, Hackeng TM, Hartmann R, Scheiflinger F, Dockal M. Direct inhibition of factor VIIa by TFPI and TFPI constructs. J Thromb Haemost 2013; 11: 704-14.
64. Dockal M, Brandstetter J, Ludwiczek M, Kontaxix G, Prohaska K, Hofbauer A, Kammlander W, Hartmann R, Ehrilich H, Scheiflinger F. Peptides binding to kunitz domain 1 of tissue factor pathway inhibitor inhibit the interaction with factor Xa. J Thromb Haemost 2011; 9: 29-30.
65. Peyvandi F, Garagiola I, Seregni S. Future of coagulation factor replacement therapy. J Thromb Haemost 2013; 11: 84-98.
66. Sehgal A, Vaishnaw A, Fitzgerald K. Liver as a target for oligonucleotide therapeutics. J Hepatol 2013; 59: 1354-9.
67. Haussecker D. Current issues of RNAi therapeutics delivery and development. J Control Release 2014; 195: 49-54.
68. Dahlman JE, Barnes C, Khan OF, Thiriot A, Jhunjunwala S, Shaw TE, Xing Y, Sager HB, Sahay G, Speciner L, Bader A, Bogorad RL, Yin H, Racie T, Dong Y, Jiang S, Seedorf D, Dave A, Singh Sandhu K, Webber MJ, et al. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. Nat Nanotechnol 2014; 9: 648-55.
69. Konkle BA, Ebbesen LS, Erhardtsen E, Bianco RP, Lissitchkov T, Rusen L, Serban MA. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors. J Thromb Haemost 2007; 5: 1904-13.