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The availability of new drugs for hemophilia treatment

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References

  • Tagliaferri A, Rivolta GF, Iorio A, et al. Mortality and causes of death in Italian persons with haemophilia, 1990-2007. Haemophilia. 2010;16:437–446.
  • Mazepa MA, Monahan PE, Baker JR, et al. Men with severe hemophilia in the United States: birth cohort analysis of a large national database. Blood. 2016;127:3073–3081.
  • High KH, Nathwani A, Spencer T, et al. Current status of haemophilia gene therapy. Haemophilia. 2014;20(Suppl 4):43–49.
  • Lieuw K. Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches? J Blood Med. 2017;8:67–73.
  • Franchini M, Mannucci PM. Non-factor replacement therapy for haemophilia: a current update. Blood Transfus. 2018;16:457–461.
  • Turecek PL, Bossard MJ, Graninger M, et al. BAX 855, a PEGylated rFVIII product with prolonged half-life: development, functional and structural characterisation. Hamostaseologie. 2012;32(Suppl 1):S29–38.
  • Konkle BA, Stasyshyn O, Chowdary P, et al. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015;126:1078–1085.
  • Mullins ES, Stasyshyn O, Alvarez-Román MT, et al. Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A. Haemophilia. 2017;23:238–246.
  • Carcao MD, Chelle P, Clarke E, et al. Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: is there a difference? J. Thromb Haemost. 2019;17:1085–1096.
  • Schmidbauer S, Witzel R, Robbel L, et al. Physicochemical characterisation of rVIII-SingleChain, a novel recombinant single-chain factor VIII. Thromb Res. 2015;136:388–395.
  • Zollner S, Raquet E, Claar P, et al. Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain, a novel recombinant single-chain factor VIII. Thromb Res. 2014;134:125–131.
  • Klamroth R, Simpson M, von Depka-prondzinski M, et al. Comparative pharmacokinetics of rVIII-SingleChain and octocog alfa (Advate(®)) in patients with severe haemophilia A. Haemophilia. 2016;22:730–738.
  • Zhang Y, Roberts J, Tortorici M, et al. Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A. J Thromb Haemost. 2017;15:1106–1114.
  • Mahlangu J, Kuliczkowski K, Karim FA, et al. Efficacy and safety of rVIII-Singlechain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A. Blood. 2016;128:630–637.
  • Stasyshyn O, Djambas Khayat C, Iosava G, et al. Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial. J Thromb Haemost. 2017;15:636–644.
  • Lillicrap D. Novel Approaches for Immune tolerance Induction. Presentation at 64th Annual meeting of the SSC of ISTH. Dubllin. 2018 July :21–28.
  • Lencer WI, Blumberg RS. A passionate kiss, then run: exocytosis and recycling of IgG by FcRn. Trends Cell Biol Elsevier Ltd. 2005;15:5–9.
  • Tang L, Leong L, Sim D, et al. von Willebrand factor contributes to longer half-life of PEGylated factor VIII in vivo. Haemophilia. 2013;19:539–545.
  • Van Der Flier A, Liu Z, Tan S, et al. FcRn rescues recombinant factor VIII Fc fusion protein from a VWF independent FVIII clearance pathway in mouse hepatocytes. PLoS One. 2015;10:e0124930.
  • Dumont JA, Liu T, Low SC, et al. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs. Blood. 2012;119:3024–3030.
  • Powell JS, Josephson NC, Quon D, et al. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood. 2012;119:3031–3037.
  • Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014;123:317–325.
  • Young G, Mahlangu J, Kulkarni R, et al. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A. J Thromb Haemost. 2015;13:967–977.
  • Mei B, Pan C, Jiang H, et al. Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment. Blood. 2010;116:270–279.
  • Shah A, Solms A, Wiegmann S, et al. Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A. Ann.Hematol. 2019;98:2035–2044.
  • Reding MT, Ng HJ, Poulsen LH, et al. Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII. J Thromb Haemost. 2017;15:411–419.
  • Lalezari S, Reding MT, Pabinger I, et al. BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results. Haemophilia. 2019;25:1011–1019.
  • DeFrees S, Wang ZG, Xing R, et al. GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli. Glycobiology. 2006;16:833–843.
  • Stennicke HR, Ostergaard H, Bayer RJ, et al. Generation and biochemical characterization of glycoPEGylated factor VIIa derivatives. Thromb Haemost. 2008;100:920–928.
  • Thim L, Vandahl B, Karlsson J, et al. Purification and characterization of a new recombinant factor VIII (N8). Haemophilia. 2010;16:349–359.
  • Martinowitz U, Bjerre J, Brand B, et al. Bioequivalence between two serum-free recombinant factor VIII preparations (N8 and ADVATE ®) - an open-label, sequential dosing pharmacokinetic study in patients with severe haemophilia A. Haemophilia. 2011;17:854–859.
  • Stennicke HR, Kjalke M, Karpf DM, et al. A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models. Blood. 2013;121:2108–2116.
  • Tiede A, Brand B, Fischer R, et al. 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;11:670–678.
  • Giangrande P, Andreeva T, Chowdary P, et al. Clinical evaluation of glycoPEGylated recombinant FVIII : efficacy and safety in severe haemophilia A. Thromb Haemost. 2017;117:252–261.
  • Curry N, Albayrak C, Escobar M, et al. Once ‐ weekly prophylaxis with glycoPEGylated recombinant factor VIII (N8 ‐ GP) in severe haemophilia A : safety and efficacy results from pathfinder 2 (randomized phase III trial). Haemophilia. 2019;25:373–381.
  • Meunier S, Alamelu J, Ehrenforth S, et al. Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A. Thromb Haemost. 2017;117:1705–1713.
  • Kannicht C, Ramström M, Kohla G, et al. Characterisation of the post-translational modifications of a novel, human cell line-derived recombinant human factor VIII. Thromb Res. 2013;131:78–88.
  • Sandberg H, Kannicht C, Stenlund P, et al. Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII. Thromb Res. 2012;130:808–817.
  • Klukowska A, Szczepański T, Vdovin V, et al. Novel, human cell line-derived recombinant factor VIII (Human-cl rhFVIII, Nuwiq®) in children with severe haemophilia A: efficacy, safety and pharmacokinetics. Haemophilia. 2016;22:232–239.
  • Shah A, Solms A, Wiegmann S, et al. Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A. Haemophilia. 2019;25:1011–1019.
  • Tiede A, Oldenburg J, Lissitchkov T, et al. Prophylaxis vs. on-demand treatment with Nuwiq® (Human-cl rhFVIII) in adults with severe haemophilia A. Haemophilia. 2016;22:374–380.
  • Liesner RJ, Abashidze M, Aleinikova O, et al. Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study. Haemophilia. 2018;24:211–220.
  • Klukowska A, Szczepański T, Vdovin V, et al. Long-term tolerability, immunogenicity and efficacy of Nuwiq® (human-cl rhFVIII) in children with severe haemophilia A. Haemophilia. 2018;24:595–603.
  • Peters RT, Low SC, Kamphaus GD, et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood. 2010;115:2057–2064.
  • Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007;7:715–725.
  • Ghetie V, Ward ES. Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Annu Rev Immunol. 2000;18:739–766.
  • Shapiro AD, Ragni MV, Valentino LA, et al. Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. Blood. 2012;119:666–672.
  • Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 Study of Recombinant Factor IX Fc Fusion Protein in Hemophilia B. N Engl J Med. 2013;369:2313–23.
  • Diao L, Li S, Ludden T, et al. Population pharmacokinetic modelling of recombinant factor IX Fc fusion protein (rFIXFc) in patients with haemophilia B. Clin Pharmacokine. 2014;53:467–477.
  • Fischer K, Kulkarni R, Nolan B, et al. Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study. Lancet Haematol. 2017;4:e75–e82.
  • Metzner HJ, Weimer T, Kronthaler U, et al. Genetic fusion to albumin improves the pharmacokinetic properties of factor IX. Thromb Haemost. 2009;102:634–44.
  • Nolte MW, Nichols TC, Mueller-Cohrs J, et al. Improved kinetics of rIX-FP, a recombinant fusion protein linking factor IX with albumin, in cynomolgus monkeys and hemophilia B dogs. J Thromb Haemost. 2012;10:1591–1599.
  • Herzog E, Harris S, Henson C, et al. Biodistribution of the recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in rats. Thromb Res. 2014;133:900–907.
  • Chaudhury C, Mehnaz S, Robinson JM, et al. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med. 2003;197:315–322.
  • Chaudhury C, Brooks CL, Carter DC, et al. Albumin binding to FcRn: distinct from the FcRn-IgG interaction. Biochemistry. 2006;45:4983–4990.
  • Kim J, Bronson CL, Hayton WL, et al. Albumin turnover: fcRn-mediated recycling saves as much albumin from degradation as the liver produces. Am J Physiol Gastrointest Liver Physiol. 2006;290:G352–60.
  • Santagostino E, Negrier C, Klamroth R, et al. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood. 2012;120:2405–2411.
  • Martinowitz U, Lissitchkov T, Lubetsky A, et al. Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients. Haemophilia. 2015;21:784–790.
  • Martinowitz U, Lubetsky A. Phase I/II, open-label, multicenter, safety, efficacy and PK study of a recombinant coagulation factor IX albumin fusion protein (rIX-FP) in subjects with hemophilia B. Thromb Res. 2013;131(Suppl 2):S11–14.
  • Santagostino E, Martinowitz U, Lissitchkov T, et al. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial. Blood. 2016;127:1761–1769.
  • Zhang Y, Roberts J, Bensen-Kennedy D, et al. Population pharmacokinetics of a new long-acting recombinant coagulation factor IX albumin fusion protein for patients with severe hemophilia B. J Thromb Haemost. 2016;14:2132–2140.
  • Kenet G, Chambost H, Male C, et al. Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children: results of a phase 3 trial. Thromb Haemost. 2016;116:659–668.
  • Østergaard H, Bjelke JR, Hansen L, et al. Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide. Blood. 2011;118:2333–2341.
  • Negrier C, Knobe K, Tiede A, et al. Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood. 2011;118:2695–2701.
  • Collins PW, Young G, Knobe K, et al. Recombinant long-acting glycoPEGylated factor IX in hemophilia B : a multinational randomized phase 3 trial. Blood. 2014;124:3880–3886.
  • Carcao M, Zak M, Karim FA, et al. Nonacog beta pegol in previously treated children with hemophilia B : results from an international open-label phase 3 trial. J Thromb Haemost. 2016:1521–1529.
  • Pasi KJ, Rangarajan S, Georgiev P, 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, 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.
  • Lauritzen B, Hilden I. Concizumab promotes haemostasis via a tissue factor-factor VIIa–dependent mechanism supporting prophylactic treatment of haemophilia: results from a rabbit haemophilia bleeding model. Haemophilia. 2019;25:e379–e382.
  • Broze GJ, Warren LA, Novotny WF, et al. The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood. 1988;71:335–343.
  • Baugh RJ, Broze GJ, Krishnaswamy S. Regulation of extrinsic pathway factor Xa formation by tissue factor pathway inhibitor. J Biol Chem. 1998;273:4378–4386.
  • Agersø H, Overgaard RV, Petersen MB, et al. 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;56:65–69.
  • Erhardtsen E, Ezban M, Madsen MT, et al. Blocking of tissue factor pathway inhibitor (TFPI) shortens the bleeding time in rabbits with antibody induced haemophilia A. Blood Coagul Fibrinolysis. 1995;6:388–394.
  • Eichler H, Angchaisuksiri P, Kavakli K, et al. A randomized trial of safety, pharmacokinetics and pharmacodynamics of concizumab in people with hemophilia A. J Thromb Haemost. 2018;16:2184–2195.
  • Shapiro AD, Angchaisuksiri P, Astermark J, et al. Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results. Blood. 2019;134:1973–1982.
  • Kitazawa T, Igawa T, Sampei Z, et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med. 2012;18:1570–1574.
  • Sampei Z, Igawa T, Soeda T, et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One. 2013;8:e57479.
  • Muto A, Yoshihashi K, Takeda M, et al. Anti-factor IXa/X bispecific antibody (ACE910): hemostatic. J Thromb Haemost. 2014;12:206–213.
  • Muto A, Yoshihashi K, Takeda M, et al. Anti-factor 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, 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.
  • Shima M, Lillicrap D, Kruse-Jarres R. Alternative therapies for the management of inhibitors. Haemophilia. 2016;22:36–41.
  • Oldenburg J, Mahlangu JN, Bujan W, et al. The effect of emicizumab prophylaxis on health-related outcomes in persons with haemophilia A with inhibitors: HAVEN 1 Study. Haemophilia. 2019;25:33–44.
  • Le Quellec S. Clinical Evidence and Safety Profile of Emicizumab for the Management of Children with Hemophilia A. Drug Des Devel Ther. 2020;14:469–481.
  • Okamoto S, Suzuki N, Suzuki A, et al. Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors. TH Open. 2019;03:e364–e366.
  • Seaman CD, Ragni MV. Emicizumab use in major orthopedic surgery. Blood Adv. 2019;3:1722–1724.
  • Batsuli G, Zimowski KL, Tickle K, et al. Immune tolerance induction in paediatric patients with haemophilia A and inhibitors receiving emicizumab prophylaxis. Haemophilia. 2019;25:789–796.
  • Collins PW, Liesner R, Makris M, et al. Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee. Haemophilia. 2018;24:344–347.
  • Castaman G, Santoro C, Coppola A, et al. Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET. Blood Transfus. 2020;18:143–151.
  • Susen S, Gruel Y, Godier A, et al. Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra®): proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP). Haemophilia. 2019;25:731–737.
  • 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.
  • Leksa NC, Aleman MM, Goodman AG, et al. Intrinsic differences between FVIIIa mimetic bispecific antibodies and FVIII prevent assignment of FVIII-equivalence. J Thromb Haemost. 2019;17:1044–1052.
  • Tripodi A, Chantarangkul V, Novembrino C, et al. Advances in the Treatment of Hemophilia: implications for Laboratory Testing. Clin Chem. 2019;65:254–262.
  • Biron‐Andreani C, Diaz‐Cau I, Ranc A, et al. Major surgery management in patients with haemophilia A and inhibitors on emicizumab prophylaxis without global coagulation monitoring. Br J Haematol. 2020;189:e100–e103.
  • Sehgal A, Barros S, Ivanciu L, et al. An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia. Nat Med. 2015;21:492–497.
  • Peyvandi F, Mannucci PM, Garagiola I, et al. A randomized trial of factor VIII and neutralizing antibodies in hemophilia. A N Engl J Med. 2016;374:2054–2064.
  • Andersson NG, Chalmers EA, Kenet G, et al. Mode of delivery in hemophilia: vaginal delivery and Cesarean section carry similar risks for intracranial hemorrhages and other major bleeds. Haematologica. 2019;104:2100–2106.
  • Chalmers EA, Alamelu J, Collins PW, et al. Intracranial haemorrhage in children with inherited bleeding disorders in the UK 2003-2015: A national cohort study. Haemophilia. 2018;24:641–647.
  • Ljung R, Petrini P, Nilsson IM. Diagnostic symptoms of severe and moderate haemophilia A and B. A survey of 140 cases. Acta Paediatr Scand. 1990;79:196–200.

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