Pharmacokinetic and safety considerations when switching from standard to extended half-life clotting factor concentrates in hemophilia

References

• Mariani G, Di Paolantonio T, Baklaya R, et al. Prospective study of the evaluation of hepatitis C virus infectivity in a high-purity, solvent/detergent-treated factor VIII concentrate: parallel evaluation of other markers for lipid-enveloped and non-lipid-enveloped viruses. The Ad Hoc Study Group of the Fondazione of hemophilia. Transfusion. 1993;33:814–818.
   PubMed Web of Science ®Google Scholar
• Goedert JJ, Brown DL, Hoots K, et al. Human immunodeficiency and hepatitis virus infections and their associated conditions and treatments among people with hemophilia. Haemophilia. 2004;10(Suppl 4):205–210.
   PubMed Web of Science ®Google Scholar
• Gabrielsson J, Weiner D. PK and PD data analysis: concepts and applications. 4th ed. Stockholm, Sweden: Swedish Pharmaceutical Press; 2006.
   Google Scholar
• Morfini M, Gherardini S. Pharmacokinetic-based prediction of real-life dosing of extended half-life clotting factor concentrates on hemophilia. Ther Adv Hematol. 2018;9:149–162.
   PubMed Web of Science ®Google Scholar
• Collins P, Chalmers E, Chowdary P, et al. The use of enhanced half-life coagulation factor concentrates in routine clinical practice: guidance from UKHCDO. Haemophilia. 2016;22:487–498.
   PubMed Web of Science ®Google Scholar
• Den Uijl IE, Mauser Bunschoten EP, Roosendaal G, et al. Clinical severity of hemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011;17:849–853.
   PubMed Web of Science ®Google Scholar
• Valentino LA, Pipe SW, Collins PW, et al. Association of peak factor VIII levels and area under the curve with bleeding in patients with hemophilia A on every third day pharmacokinetic-guided prophylaxis. Haemophilia. 2016;22:514–520.
   PubMed Web of Science ®Google Scholar
• Warrier I, Baird-Cox K, Lusher JM. Use of central venous catheters in children with haemophilia: one haemophilia treatment centre experience. Haemophilia. 1997;3:194–198.
   PubMed Web of Science ®Google Scholar
• Furlan R, Krishnan S, Vietri J. Patient and parent preferences for characteristics of prophylactic treatment in hemophilia. Patient Prefer Adherence. 2015;9:1687–1694.
   PubMed Web of Science ®Google Scholar
• Von Mackensen S, Eldar-Lissai A, Auguste P, et al. Measurement properties of the Haem-A-QoL in haemophilia clinical trials. Haemophilia. 2017;23:383–391.
   PubMed Web of Science ®Google Scholar
• Mancuso ME, Santagostino E. Outcome of clinical trials with new extended half-life FVIII/IX concentrates. J Clin Med. 2017;6:E39.
   PubMed Web of Science ®Google Scholar
• Carcao M. Switching from current factor VIII (FVIII) to longer acting FVIII concentrates--what is the real potential benefit? Haemophilia. 2015;21:297–299.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hermans C, Mahlangu J, Booth J, et al. Pharmacokinetic modelling and validation of the half-life extension needed to reduce the burden of infusions compared with standard factor VIII. Haemophilia. 2018;24:376–384.
   PubMed Web of Science ®Google Scholar
• Berntorp E. Andersson NG. Prophylaxis for hemophilia in the era of extended half-life factor VIII/Factor IX products. Semin Thromb Hemost. 2016;42:518–525.
   PubMed Web of Science ®Google Scholar
• Björkman S, Shapiro AD, Berntorp E. Pharmacokinetics of recombinant factor IX in relation to age of the patient: implication for dosing in prophylaxis. Haemophilia. 2001;7:133–139.
   PubMed Web of Science ®Google Scholar
• Stafford DW. Extravascular FIX and coagulation. Thromb J. 2016;14(Suppl1):35.
   PubMedGoogle Scholar
• Metzner HJ, Weimer T, Kronthaler U, et al. Genetic fusion to albumin improves the pharmacokinetic properties of factor IX. Thromb Haemost. 2009;102:634–644.
   PubMed Web of Science ®Google Scholar
• Peters RT, Low SC, Kamphaus GD, et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood. 2010;115:2057–2064.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Powell JS, Pasi KJ, Ragni MV, et al. B-LONG investigators. phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013;369:2313–2323.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Broderick CR, Herbert RD, Latimer J, et al. Association between physical activity and risk of bleeding in children with haemophilia. JAMA. 2012;308:1452–1459.
   PubMed Web of Science ®Google Scholar
• Herbert RD, Broderick CR, Barnes C, et al. Optimization of prophylaxis for hemophilia A. PLoS One. 2018;13:e0192783.
   PubMed Web of Science ®Google Scholar
• Konkle BA, Stasyshyn O, Chowdary P, et al. Pegylated, full-length, recombinant factor VIII for the prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015;126:1078–1085.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Nolan B, Mahlangu J, Perry D, et al. Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A. Haemophilia. 2016;22:72–80.
   PubMed Web of Science ®Google Scholar
• Giangrande P, Chowdary P, Enhrenforth S, et al. Clinical evaluation of glycopPEGylated recombinant FVIII: efficay and safety in severe haemophilia A. J Thromb Haemost. 2017;117:252–256.
   Google Scholar
• 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;369:2313–2323.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Collins PW, Young G, Knobe K, et al. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational, randomized phase3 trial. Blood. 2014;124:3880–3886.
   PubMed Web of Science ®Google Scholar
• Gringeri A, Ewenstein B, Reininger A. The burden of bleeding in haemophilia: is one bleed too many? Haemophilia. 2014;20:459–463.
   PubMed Web of Science ®Google Scholar
• Mahlangu J. rFVIIIFC for hemophilia A prophylaxis. Expert Rev Hematol. 2018;11:937–943.
   PubMed Web of Science ®Google Scholar
• Santagostino E, Mancuso ME. GlycoPEGylated recombinant factor IX for hemophilia B in context. Drug Des Devel Ther. 2018;12:2933–2943.
   PubMed Web of Science ®Google Scholar
• Chowdary P, Kearney S, Regnault A, et al. Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product. Haemophilia. 2016;22:e267–74.
   PubMed Web of Science ®Google Scholar
• Von Mackensen S, Shah J, Seifert W, et al. Health-related quality of life in paediatric haemophilia B patients treated with rIX-FP. Haemophilia. 2018. DOI:10.1111/hae.13624
   Google Scholar
• Morfini M, Lee M, Messori A. The design and analysis of half-life and recovery studies for factor VIII and factor IX. Factor VIII/Factor IX scientific and standardization committee of the international society for thrombosis and haemostasis. Thromb Haemost. 1991;66:384–386.
   PubMed Web of Science ®Google Scholar
• Lee M, Morfini M, Schulman S, et al. The factor VIII/factor IX scientific and standardization committee of the ITSH the design and analysis of pharmacokinetic studies of coagulation factors. [cited 2019 Jun 14]. Available from: https://cdn.ymaws.com/www.isth.org/resource/group/d4a6f49a-f4ec-450f-9e0f- 7be9f0c2ab2e/official communications/fviiipharmaco.pdf
   Google Scholar
• Björkman S, Oh M, Spotts G, et al. Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight. Blood. 2012;119:612–618.
   PubMed Web of Science ®Google Scholar
• Iorio A, Keepanasseril A, Foster G, et al. Hemo co-investigator network. Development of a web-accessible population pharmacokinetic service-hemophilia (WAPPS-Hemo): study protocol. JMIR Res Protoc. 2016;5:e239.
   PubMed Web of Science ®Google Scholar
• Staibano P, McEnenyKing A, Morfini M, et al. Comparative assessment of the performance of pharmacokinetic tools for prophylactic dosing of antihemophilic factor recombinant plasma/albumin-free method (rAHF-PFM) concentrate in patients with hemophilia A. Blood. 2017;130:4934.
   Web of Science ®Google Scholar
• Blanchette VS, Tiseo L, Lillicrap D, et al. A practical, one clinic visit, population pharmacokinetic (PK) protocol for generation of pk profiles in subjects with severe hemophilia A abstract 2480. ASH. 2018.
   Google Scholar
• Di Paola J, Smith MP, Klamroth R, et al. ReFacto and Advate: a single-dose, randomized, two-period crossover pharmacokinetic study in subjects with haemophilia A. Haemophilia. 2007;13:124–130.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Carlsson M, Berntorp E, Björkman S, et al. Improved cost-effectiveness by pharmacokinetic dosing of factor VIII in prophylactic treatment of haemophilia A. Haemophilia. 1997;3:96–101.
   PubMed Web of Science ®Google Scholar
• Carlsson M, Björkman S. Berntorp E Multidose pharmacokinetics of factor IX: implications for dosing in prophylaxis. Haemophilia. 1998;4:83–88.
   PubMed Web of Science ®Google Scholar
• Hassan S, Cannavò A, Gouw SC, et al. Factor VIII products and inhibitor development in previously treated patients with severe or moderately severe hemophilia A: a systematic review. Thromb Haemost. 2018;16:1055–1068.
   Web of Science ®Google Scholar
• Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products. [cited 2019 Jun 14]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/06/WC500187409.pdf
   Google Scholar
• Guideline on clinical investigation of recombinant and human plasma-derived factor IX products. [cited 2019 Jun 14]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/06/WC500187413.pdf
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Lillicrap D. Novel approaches for immune tolerance induction. Abstracts of the 64th Annual Meeting of the SSC of ISTH, July 18–21, 2018. J Thromb Haemost 2019;17:7.
   Google Scholar
• Hay CR. The 2000 United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO) inhibitor guidelines. Pathophysiol Haemost Thromb. 2002;32(Suppl 1):19–21.
   PubMedGoogle Scholar
• Gringeri A, Lundin B, von Mackensen S, et al. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). J Thromb Haemost. 2011;9:700–710.
   PubMed Web of Science ®Google Scholar
• Pradelli L, Villa S, Castaman G. Albutrepenonacog alfa (Idelvion R) for the treatment of Italian patients with haemophilia B: a budget impact model Farmeconomia. Health Econ Ther Pathways. 2018;19:1–10.
   Web of Science ®Google Scholar
• Tortella BJ, Alvir J, McDonald M, et al. Real-world analysis of dispensed IUs of coagulation factor IX and resultant expenditures in hemophilia B patients receiving standard half-life versus extended half-life products and those switching from standard half-life to extended half-life products. J Manag Care Spec Pharm. 2018;24:643–653.
   PubMed Web of Science ®Google Scholar
• Pool JG, Hink JH. Experiences in the preparation of AHG concentrates from human plasma. Bibl Haematol. 1964;19:146–150.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Waters EK, Sigh J, Friedrich U, et al. Concizumab, an anti-tissue factor pathway inhibitor antibody induces increased thrombin generation in plasma from haemophilia patients and healthy subjects measured by the thrombin generation assay. Haemophilia. 2017;23:769–776.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Brummel-Ziedins KE, Whelihan MF, Rivard GE, et al. Activated protein C inhibitor for correction of thrombin generation in hemophilia A blood and plasma1. J Thromb Haemost. 2011;9:2262–2267.
   PubMed Web of Science ®Google Scholar
• Shima M, Hanabusa H, Taki M, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med. 2016;374:2044–2053.
   PubMed Web of Science ®Google Scholar
• Minami H, Nogami K, Soeda T, et al. The factor VIII heavy chain improves emicizumab-tenase assembly to enhance the factor VIII-mimicking cofactor activity. Thromb Res. 2018;166:77–79.
   PubMed Web of Science ®Google Scholar
• Shima M, Lillicrap D, Kruse-Jarres R. Alternative therapies for the management of inhibitors. Haemophilia. 2016;22(Suppl 5):36–41.
   PubMed Web of Science ®Google Scholar
• An expanded access program of emicizumab in participants with hemophilia A with inhibitors. ClinicalTrials.gov Identifier: NCT03154437. [cited 2019 Jun 14]. Available from: https://clinicaltrials.gov/ ct2/show/NCT03154437
   Google Scholar
• Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357:535–544.
   PubMed Web of Science ®Google Scholar
• Guidance for industry-exposure-response relationships - study design, data analysis, and regulatory applications. [cited 2019 Jun 14]. Available from: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072109.pdf
   Google Scholar
• Drager D, Patarroyo-White S, Chao H, et al. Recombinant FVIIIFc-VWF-XTEN demonstrates significant bioavailability following subcutaneous administration in hemophilia A mice. Abstract at 57th ASH annual meeting. Blood. 3492;23:126.
   Google Scholar