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Lonoctocog alfa (rVIII-SingleChain) for the treatment of haemophilia A.

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Raso, Simona Hermans, Cédric [UCL]

The administration of factor VIII (FVIII) concentrates on-demand or on long-term prophylaxis is the effective and safe standard of care of patients with hemophilia A (HA). Development of neutralizing antibodies against exogenous FVIII and the short half-life of the current available products remain major challenges. There is currently a great interest towards newer FVIII products with the goal of reducing the inhibitor risk and increasing the half-life. Area covered: In this review, the authors describe the efficacy and safety of rVIII-SingleChain (Lonoctocog alfa), the first and only single chain recombinant FVIII (rFVIII) molecule developed for the prevention and treatment of bleeding episodes in HA patients. The pre-clinical and clinical studies of rVIII-SingleChain as well as the results of the AFFINITY trial program in previously treated patients both adults and pediatric are presented and discussed. Expert opinion: The results from PTP studies document the efficacy and safety profile of the rVIII-SingleChain. However, even if rFVIII-SingleChain presents advantageous pharmacokinetic features compared to conventional rFVIII, it should not be considered as an EHL-FVIII while its immunogenicity is currently being studied in PUPs. The slightly better PK profile of rFVIII-SingleChain could however allow a small number of selected patients to be treated with a less intensive regimen.

Document type Article de périodique (Journal article) – Synthèse de littérature
Publication date 2018
Language Anglais
Journal information "Expert Opinion on Biological Therapy" - Vol. 18, no.1, p. 87-94 (2018)
Peer reviewed yes
Publisher Taylor & Francis ((United Kingdom) Oxford)
issn 1471-2598
e-issn 1744-7682
Publication status Publié
Affiliations UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire
UCL - (SLuc) Service d'hématologie
MESH Subject Clinical Trials as Topic ; Coagulants ; Factor VIII ; Half-Life ; Hemophilia A ; Humans ; Recombinant Proteins
Keywords Haemophilia ; factor VIII ; single-chain
Links
  1. Franchini Massimo, Mannucci Pier, The History of Hemophilia, 10.1055/s-0034-1381232
  2. Franchini Massimo, Mannucci Pier Mannuccio, Hemophilia A in the third millennium, 10.1016/j.blre.2013.06.002
  3. Berntorp E., Prophylactic therapy for haemophilia: early experience, 10.1046/j.1365-2516.9.s1.3.x
  4. Oldenburg J., Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens, 10.1182/blood-2015-01-528414
  5. DE MOERLOOSE P., URBANCIK W., VAN DEN BERG H. M., RICHARDS M., A survey of adherence to haemophilia therapy in six European countries: results and recommendations, 10.1111/j.1365-2516.2008.01843.x
  6. DUNCAN N., SHAPIRO A., YE X., EPSTEIN J., LUO M. P., Treatment patterns, health-related quality of life and adherence to prophylaxis among haemophilia A patients in the United States : TREATMENT PATTERNS, QUALITY OF LIFE AND ADHERENCE, 10.1111/j.1365-2516.2012.02813.x
  7. Dumont J. A., Liu T., Low S. C., Zhang X., Kamphaus G., Sakorafas P., Fraley C., Drager D., Reidy T., McCue J., Franck H. W. G., Merricks E. P., Nichols T. C., Bitonti A. J., Pierce G. F., Jiang H., Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs, 10.1182/blood-2011-08-367813
  8. Stennicke H. R., Kjalke M., Karpf D. M., Balling K. W., Johansen P. B., Elm T., Ovlisen K., Moller F., Holmberg H. L., Gudme C. N., Persson E., Hilden I., Pelzer H., Rahbek-Nielsen H., Jespersgaard C., Bogsnes A., Pedersen A. A., Kristensen A. K., Peschke B., Kappers W., Rode F., Thim L., Tranholm M., Ezban M., Olsen E. H. N., Bjorn S. E., A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models, 10.1182/blood-2012-01-407494
  9. Ragni Margaret V., New and Emerging Agents for the Treatment of Hemophilia: Focus on Extended Half-Life Recombinant Clotting Proteins, 10.1007/s40265-015-0451-5
  10. Kepa S., Horvath B., Reitter-Pfoertner S., Schemper M., Quehenberger P., Grundbichler M., Heistinger M., Neumeister P., Mannhalter C., Pabinger I., Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A, 10.1111/hae.12592
  11. Vlot AJ, Blood, 87, 1809 (1996)
  12. Dasgupta S., Repesse Y., Bayry J., Navarrete A.-M., Wootla B., Delignat S., Irinopoulou T., Kamate C., Saint-Remy J.-M., Jacquemin M., Lenting P. J., Borel-Derlon A., Kaveri S. V., Lacroix-Desmazes S., VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors, 10.1182/blood-2006-05-022756
  13. MINNO M. N. D. DI, MINNO G. DI, CAPUA M. DI, CERBONE A. M., COPPOLA A., Cost of care of haemophilia with inhibitors, 10.1111/j.1365-2516.2009.02100.x
  14. DIMICHELE D. M., HOOTS W. K., PIPE S. W., RIVARD G. E., SANTAGOSTINO E., International workshop on immune tolerance induction: consensus recommendations, 10.1111/j.1365-2516.2007.01497.x
  15. ASTERMARK J., Inhibitor development: patient-determined risk factors : RISK FACTORS FOR INHIBITOR DEVELOPMENT, 10.1111/j.1365-2516.2008.01923.x
  16. SAENKO E. L., ANANYEVA N. M., Receptor-mediated clearance of factor VIII: implications for pharmacokinetic studies in individuals with haemophilia, 10.1111/j.1365-2516.2006.01329.x
  17. KAVERI S. V., DASGUPTA S., ANDRE S., NAVARRETE A.-M., REPESSÉ Y., WOOTLA B., LACROIX-DESMAZES S., Factor VIII inhibitors: role of von Willebrand factor on the uptake of factor VIII by dendritic cells : FACTOR VIII INHIBITORS, 10.1111/j.1365-2516.2007.01575.x
  18. Lacroix-Desmazes S., Navarrete A.-M., Andre S., Bayry J., Kaveri S. V., Dasgupta S., Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A, 10.1182/blood-2008-02-124941
  19. Pipe S. W., Montgomery R. R., Pratt K. P., Lenting P. J., Lillicrap D., Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A, 10.1182/blood-2016-04-713289
  20. ETTINGSHAUSEN C. ESCURIOLA, KREUZ W., Recombinant vs. plasma-derived products, especially those with intact VWF, regarding inhibitor development, 10.1111/j.1365-2516.2006.01373.x
  21. Behrmann M, Thromb Haemost, 88, 221 (2002)
  22. Goudemand Jenny, Laurian Yves, Calvez Thierry, Risk of inhibitors in haemophilia and the type of factor replacement : , 10.1097/01.moh.0000239702.40297.ec
  23. IORIO A., HALIMEH S., HOLZHAUER S., GOLDENBERG N., MARCHESINI E., MARCUCCI M., YOUNG G., BIDLINGMAIER C., BRANDAO L. R., ETTINGSHAUSEN C. E., GRINGERI A., KENET G., KNÖFLER R., KREUZ W., KURNIK K., MANNER D., SANTAGOSTINO E., MANNUCCI P. M., NOWAK-GÖTTL U., Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review : Inhibitor rate after plasma-derived or recombinant FVIII concentrates, 10.1111/j.1538-7836.2010.03823.x
  24. Goudemand J., Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A, 10.1182/blood-2005-04-1371
  25. Coppola Antonio, Rocino Angiola, Santagostino Elena, Tagliaferri Annarita, Zanon Ezio, Morfini Massimo, Franchini Massimo, , Systematic Review of the Role of FVIII Concentrates in Inhibitor Development in Previously Untreated Patients with Severe Hemophilia A: A 2013 Update, 10.1055/s-0033-1356715
  26. Gouw S. C., van der Bom J. G., Auerswald G., Ettinghausen C. E., Tedgard U., van den Berg H. M., , Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study, 10.1182/blood-2006-11-056317
  27. Peyvandi Flora, Mannucci Pier M., Garagiola Isabella, El-Beshlawy Amal, Elalfy Mohsen, Ramanan Vijay, Eshghi Peyman, Hanagavadi Suresh, Varadarajan Ramabadran, Karimi Mehran, Manglani Mamta V., Ross Cecil, Young Guy, Seth Tulika, Apte Shashikant, Nayak Dinesh M., Santagostino Elena, Mancuso Maria Elisa, Sandoval Gonzalez Adriana C., Mahlangu Johnny N., Bonanad Boix Santiago, Cerqueira Monica, Ewing Nadia P., Male Christoph, Owaidah Tarek, Soto Arellano Veronica, Kobrinsky Nathan L., Majumdar Suvankar, Perez Garrido Rosario, Sachdeva Anupam, Simpson Mindy, Thomas Mathew, Zanon Ezio, Antmen Bulent, Kavakli Kaan, Manco-Johnson Marilyn J., Martinez Monica, Marzouka Esperanza, Mazzucconi Maria G., Neme Daniela, Palomo Bravo Angeles, Paredes Aguilera Rogelio, Prezotti Alessandra, Schmitt Klaus, Wicklund Brian M., Zulfikar Bulent, Rosendaal Frits R., A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A, 10.1056/nejmoa1516437
  28. Fischer K., Blatny J., Do the SIPPET study results apply to the patients I treat?, 10.1111/hae.13133
  29. Gouw S. C., van den Berg H. M., Fischer K., Auerswald G., Carcao M., Chalmers E., Chambost H., Kurnik K., Liesner R., Petrini P., Platokouki H., Altisent C., Oldenburg J., Nolan B., Garrido R. P., Mancuso M. E., Rafowicz A., Williams M., Clausen N., Middelburg R. A., Ljung R., van der Bom J. G., , Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study, 10.1182/blood-2012-09-457036
  30. Schmidbauer Stefan, Witzel Reinhild, Robbel Lars, Sebastian Petra, Grammel Nicolas, Metzner Hubert J., Schulte Stefan, Physicochemical characterisation of rVIII-SingleChain, a novel recombinant single-chain factor VIII, 10.1016/j.thromres.2015.05.005
  31. Sawamoto Y, Thromb Haemost, 79, 62 (1998)
  32. Zollner Sabine, Raquet Elmar, Claar Philipp, Müller-Cohrs Jochen, Metzner Hubert J., Weimer Thomas, Pragst Ingo, Dickneite Gerhard, Schulte Stefan, Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain, a novel recombinant single-chain factor VIII, 10.1016/j.thromres.2014.03.028
  33. Zollner Sabine B., Raquet Elmar, Müller-Cohrs Jochen, Metzner Hubert J., Weimer Thomas, Pragst Ingo, Dickneite Gerhard, Schulte Stefan, Preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII, 10.1016/j.thromres.2013.06.017
  34. Mahlangu J., Kuliczkowski K., Karim F. A., Stasyshyn O., Kosinova M. V., Lepatan L. M., Skotnicki A., Boggio L. N., Klamroth R., Oldenburg J., Hellmann A., Santagostino E., Baker R. I., Fischer K., Gill J. C., PNg S., Chowdary P., Escobar M. A., Khayat C. D., Rusen L., Bensen-Kennedy D., Blackman N., Limsakun T., Veldman A., St. Ledger K., Pabinger I., , Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A, 10.1182/blood-2016-01-687434
  35. Stasyshyn O., Djambas Khayat C., Iosava G., Ong J., Abdul Karim F., Fischer K., Veldman A., Blackman N., St. Ledger K., Pabinger I., Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial, 10.1111/jth.13647
  36. Tiede A., Brand B., Fischer R., Kavakli K., Lentz S. R., 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, 10.1111/jth.12161
  37. Powell J. S., Josephson N. C., Quon D., Ragni M. V., Cheng G., Li E., Jiang H., Li L., Dumont J. A., Goyal J., Zhang X., Sommer J., McCue J., Barbetti M., Luk A., Pierce G. F., Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients, 10.1182/blood-2011-09-382846
  38. Coyle T. E., Reding M. T., Lin J. C., Michaels L. A., Shah A., Powell J., 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, 10.1111/jth.12506
  39. Carlsson M., Berntorp E., Björkman S., Lindvall K., Pharmacokinetic dosing in prophylactic treatment of hemophilia A, 10.1111/j.1600-0609.1993.tb00638.x
  40. Steele M. R., Nagel K., Chan A. K. C., Pharmacokinetics of recombinant and plasma-derived factor VIII products in paediatric patients with severe haemophilia A, 10.1111/hae.12310
  41. BLANCHETTE V. S., SHAPIRO A. D., LIESNER R. J., HERNNDEZ NAVARRO F., WARRIER I., SCHROTH P. C., SPOTTS G., EWENSTEIN B. M., , Plasma and albumin-free recombinant factorVIII: pharmacokinetics, efficacy and safety in previously treated pediatric patients, 10.1111/j.1538-7836.2008.03032.x
  42. Bj??rkman Sven, Berntorp Erik, Pharmacokinetics of Coagulation Factors : Clinical Relevance for Patients with Haemophilia, 10.2165/00003088-200140110-00003
  43. Zhang Y., Roberts J., Tortorici M., Veldman A., St Ledger K., Feussner A., Sidhu J., Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A, 10.1111/jth.13662
  44. Cannavò Antonino, Valsecchi Carla, Garagiola Isabella, Palla Roberta, Mannucci Pier Mannuccio, Rosendaal Frits R., Peyvandi Flora, Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A, 10.1182/blood-2016-06-720086
  45. St Ledger K, Haemophilia, 22, 59 (2016)
  46. Morfini M., Cinotti S., Bellatreccia A., Paladino E., Gringeri A., Mannucci P. M., , A multicenter pharmacokinetic study of the B-domain deleted recombinant factor VIII concentrate using different assays and standards, 10.1046/j.1538-7836.2003.00481.x
  47. Ingerslev J., Jankowski M. A., Weston S. B., Charles L. A., the ReFacto Field Study Participant, Collaborative field study on the utility of a BDD factor VIII concentrate standard in the estimation of BDDr Factor VIII:C activity in hemophilic plasma using one-stage clotting assays, 10.1111/j.1538-7836.2004.00657.x
  48. Lentz S. R., Misgav M., Ozelo M., Šalek S. Z., Veljkovic D., Recht M., Cerqueira M., Tiede A., Brand B., Mancuso M. E., Seremetis S., Lindblom A., Martinowitz U., Results from a large multinational clinical trial (guardian™1) using prophylactic treatment with turoctocog alfa in adolescent and adult patients with severe haemophilia A: safety and efficacy, 10.1111/hae.12159
  49. Pouplard C., Ternisien C., Desconclois C., Lasne D., Aillaud M.-F., Caron C., Discrepancies between one stage assay and chromogenic substrate assay in patients treated with recombinant or plasma-derived FVIII and usefulness of a specific standard in ReFacto AF®-treated patients, 10.1111/hae.12867
  50. Valentino L. A., Negrier C., Kohla G., Tiede A., Liesner R., Hart D., Knaub S., The first recombinant FVIII produced in human cells - an update on its clinical development programme, 10.1111/hae.12322
  51. Tarantino M. D., Collins P. W., Hay C. R. M., Shapiro A.D., Gruppo R. A., Berntorp E., Bray G. L., Tonetta S. A., Schroth P. C., Retzios A. D., Rogy S. S., Sensel M. G., Ewenstein B. M., , Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A1, 10.1111/j.1365-2516.2004.00932.x
  52. Mahlangu J., Powell J. S., Ragni M. V., Chowdary P., Josephson N. C., Pabinger I., Hanabusa H., Gupta N., Kulkarni R., Fogarty P., Perry D., Shapiro A., Pasi K. J., Apte S., Nestorov I., Jiang H., Li S., Neelakantan S., Cristiano L. M., Goyal J., Sommer J. M., Dumont J. A., Dodd N., Nugent K., Vigliani G., Luk A., Brennan A., Pierce G. F., , Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A, 10.1182/blood-2013-10-529974
  53. Konkle B. A., Stasyshyn O., Chowdary P., Bevan D. H., Mant T., Shima M., Engl W., Dyck-Jones J., Fuerlinger M., Patrone L., Ewenstein B., Abbuehl B., Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A, 10.1182/blood-2015-03-630897
  54. Kitchen S., Kershaw G., Tiefenbacher S., Recombinant to modified factor VIII and factor IX - chromogenic and one-stage assays issues, 10.1111/hae.13012
  55. Collins P., Chalmers E., Chowdary P., Keeling D., Mathias M., O'Donnell J., Pasi K. J., Rangarajan S., Thomas A., The use of enhanced half-life coagulation factor concentrates in routine clinical practice: guidance from UKHCDO, 10.1111/hae.13013
  56. Maraskovsky AE, Blood, 128, 4960 Absract (2016)
  57. Auerswald G, Haematologica, 88(6) (2003)
  58. Ettingshausen Carmen Escuriola, Kreuz Wolfhart, Role of von Willebrand factor in immune tolerance induction : , 10.1097/01.mbc.0000167660.30886.e9
  59. Kreuz W., Escuriola Ettingshausen C., Vdovin V., Zozulya N., Plyushch O., Svirin P., Andreeva T., Bubanská E., Campos M., Benedik-Dolničar M., Jiménez-Yuste V., Kitanovski L., Klukowska A., Momot A., Osmulskaya N., Prieto M., Šalek S. Z., Velasco F., Pavlova A., Oldenburg J., Knaub S., Jansen M., Belyanskaya L., Walter O., , First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study, 10.1111/hae.12774
  60. Robertson Jeremy D., Higgins Pauline, Price Jamie, Dunkley Scott, Barrese Giulio, Curtin Julie, Immune tolerance induction using a factor VIII/von Willebrand factor concentrate (BIOSTATE®), with or without immunosuppression, in Australian paediatric severe haemophilia A patients with high titre inhibitors: A multicentre, retrospective study, 10.1016/j.thromres.2014.09.010
  61. Wight J., Paisley S., Knight C., Immune tolerance induction in patients with haemophilia A with inhibitors: a systematic review, 10.1046/j.1365-2516.2003.00781.x
Bibliographic reference Raso, Simona ; Hermans, Cédric. Lonoctocog alfa (rVIII-SingleChain) for the treatment of haemophilia A.. In: Expert Opinion on Biological Therapy, Vol. 18, no.1, p. 87-94 (2018)
Permanent URL http://hdl.handle.net/2078.1/208141