, Volume 79, Issue 10, pp 1147–1156 | Cite as

Damoctocog Alfa Pegol: A Review in Haemophilia A

  • Julia PaikEmail author
  • Emma D. Deeks
Adis Drug Evaluation


Damoctocog alfa pegol (Jivi®) is approved in the USA, EU, Japan and Canada for the treatment and prophylaxis of previously treated patients aged ≥ 12 years with haemophilia A. Formulated with a 60 kDa polyethylene glycol (PEG) moiety, damoctocog alfa pegol is an intravenously (IV) administered recombinant factor VIII (rFVIII) product with a longer terminal half-life than non-PEGylated FVIII and rFVIII products. In the multinational phase II/III PROTECT VIII trial, prophylaxis with damoctocog alfa pegol reduced the likelihood of bleeding in previously treated patients aged ≥ 12 years with severe haemophilia A, with dosing schedules ranging from twice weekly to once every 7 days. Interim data from the ongoing extension phase indicated that the reduced annualized bleeding rates (ABRs) were maintained for up to 5.2 years of prophylaxis with damoctocog alfa pegol. Damoctocog alfa pegol was also effective in treating bleeding episodes and in providing haemostatic control during surgery. Damoctocog alfa pegol was generally well tolerated in adult and adolescent patients with severe haemophilia A, with most adverse events considered to be unrelated to treatment. There were no new or confirmed cases of FVIII inhibitor development and anti-PEG antibodies, observed in some patients, were of low titre and transient. Damoctocog alfa pegol extends the available treatment options in previously treated adults and adolescents with haemophilia A, offering the possibility of up to once-weekly administration for suitable patients.



During the peer review process, the manufacturer of damoctocog alfa pegol was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards


The preparation of this review was not supported by any external funding.

Conflicts of interest

Julia Paik and Emma Deeks are salaried employees of Adis International Ltd/Springer Nature, are responsible for the article content and declare no relevant conflicts of interest.


  1. 1.
    Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1–47.CrossRefGoogle Scholar
  2. 2.
    Srivastava A. Haemophilia care: beyond the treatment guidelines. Haemophilia. 2014;20(Suppl 4):4–10.CrossRefGoogle Scholar
  3. 3.
    Petrini P, Valentino LA, Gringeri A, et al. Individualizing prophylaxis in hemophilia: a review. Expert Rev Hematol. 2015;8(2):237–46.CrossRefGoogle Scholar
  4. 4.
    Bjorkman S, Folkesson A, Jonsson S. Pharmacokinetics and dose requirements of factor VIII over the age range 3-74 years: a population analysis based on 50 patients with long-term prophylactic treatment for haemophilia A. Eur J Clin Pharmacol. 2009;65(10):989–98.CrossRefGoogle Scholar
  5. 5.
    Saxena K. Barriers and perceived limitations to early treatment of hemophilia. J Blood Med. 2013;4:49–56.CrossRefGoogle Scholar
  6. 6.
    Scharrer I, Bray GL, Neutzling O. Incidence of inhibitors in haemophilia A patients: a review of recent studies of recombinant and plasma-derived factor VIII concentrates. Haemophilia. 1999;5(3):145–54.CrossRefGoogle Scholar
  7. 7.
    Witmer C, Young G. Factor VIII inhibitors in hemophilia A: rationale and latest evidence. Ther Adv Hematol. 2013;4(1):59–72.CrossRefGoogle Scholar
  8. 8.
    Lieuw K. Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches? J Blood Med. 2017;8:67–73.CrossRefGoogle Scholar
  9. 9.
    Miao HZ, Sirachainan N, Palmer L, et al. Bioengineering of coagulation factor VIII for improved secretion. Blood. 2004;103(9):3412–9.CrossRefGoogle Scholar
  10. 10.
    Ivens IA, Baumann A, McDonald TA, et al. PEGylated therapeutic proteins for haemophilia treatment: a review for haemophilia caregivers. Haemophilia. 2013;19(1):11–20.CrossRefGoogle Scholar
  11. 11.
    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(2):270–9.CrossRefGoogle Scholar
  12. 12.
    Ivens IA, Achanzar W, Baumann A, et al. PEGylated biopharmaceuticals: current experience and considerations for nonclinical development. Toxicol Pathol. 2015;43(7):959–83.CrossRefGoogle Scholar
  13. 13.
    US Food and Drug Administration. JIVI (antihemophilic factor (recombinant), PEGylated-aucl): clinical review. 2018. Accessed 6 June 2019.
  14. 14.
    European Medicines Agency. Damoctocog alfa pegol (Jivi): EU summary of product characteristics. 2018. Accessed 6 June 2019.
  15. 15.
    Pharmaceuticals and Medical Devices Agency. Jivi® for IV injection: Japanese prescribing information. 2018. Accessed 6 June 2019.
  16. 16.
    Bayer HealthCare LLC. JIVI® [antihemophilic factor (recombinant), B-domain deleted, PEGylated]: Canadian product monograph. 2018. Accessed 6 June 2019.
  17. 17.
    Bayer HealthCare LLC. JIVI® [antihemophilic factor (recombinant), PEGylated-aucl]: US prescribing information. 2018. Accessed 6 June 2019.
  18. 18.
    Saenko EL, Yakhyaev AV, Mikhailenko I, et al. Role of the low density lipoprotein-related protein receptor in mediation of factor VIII catabolism. J Biol Chem. 1999;274(53):37685–92.CrossRefGoogle Scholar
  19. 19.
    Lenting PJ, Neels JG, van den Berg BM, et al. The light chain of factor VIII comprises a binding site for low density lipoprotein receptor-related protein. J Biol Chem. 1999;274(34):23734–9.CrossRefGoogle Scholar
  20. 20.
    Bovenschen N, Boertjes RC, van Stempvoort G, et al. Low density lipoprotein receptor-related protein and factor IXa share structural requirements for binding to the A3 domain of coagulation factor VIII. J Biol Chem. 2003;278(11):9370–7.CrossRefGoogle Scholar
  21. 21.
    Chiu PL, Bou-Assaf GM, Chhabra ES, et al. Mapping the interaction between factor VIII and von Willebrand factor by electron microscopy and mass spectrometry. Blood. 2015;126(8):935–8.CrossRefGoogle Scholar
  22. 22.
    Weiss HJ, Sussman II, Hoyer LW. Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand’s disease. J Clin Invest. 1977;60(2):390–404.CrossRefGoogle Scholar
  23. 23.
    Yada K, Nogami K, Patel C, et al. A factor VIII with site-specific PEGylation attenuates the binding with inhibitors results in the retention of hemostatic effect [abstract]. Blood. 2015;126(23):1076.Google Scholar
  24. 24.
    Maas Enriquez M, Katterle Y, Baumann A, et al. BAY 94-9027 PROTECT VIII studies: observation of pharmacokinetic steady state for 60-kDa PEG demonstrates the existence of elimination processes for PEG [abstract no. T-FPMED02-002 (600)]. Haemophilia. 2018;24(Suppl 5):16.Google Scholar
  25. 25.
    Coyle TE, Reding MT, Lin JC, 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. J Thromb Haemost. 2014;12(4):488–96.CrossRefGoogle Scholar
  26. 26.
    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(3):411–9.CrossRefGoogle Scholar
  27. 27.
    Shah A, Coyle T, Lalezari S, et al. BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life and higher area under the curve in patients with severe haemophilia A: comprehensive pharmacokinetic assessment from clinical studies. Haemophilia. 2018;24(5):733–40.CrossRefGoogle Scholar
  28. 28.
    Ahsman M, Vis P, Shah A, et al. Predictable and reliable individualized pharmacokinetic profiling with BAY 94-9027: integrated population pharmacokinetics analysis [abstract no. T-P-092 (372)]. Haemophilia. 2018;24(Suppl 5):89–90.Google Scholar
  29. 29.
    Thomson G, Holme PA, Wang M, et al. Effective protection for > 5 years with BAY 94-9027 prophylaxis: interim results from the PROTECT VIII extension trial [abstract plus poster]. In: The 11th Annual Congress of the European Association for Haemophilia and Allied Disorders. 2018.Google Scholar
  30. 30.
    Santagostino E, Lalezari S, Ducore J, et al. BAY 94-9027 is efficacious in maintaining hemostasis during major surgery in adults and adolescents with severe hemophilia A: PROTECT VIII results [abstract no. P079]. Haemophilia. 2018;24(Suppl 1):69.Google Scholar
  31. 31.
    European Medicines Agency. Jivi (damoctocog alfa pegol): public assessment report. 2019. Accessed 6 June 2019.
  32. 32.
    Oldenburg J, Michaels LA, Wang M, et al. PROTECT VIII: can patient characteristics predict eligibility for less frequent prophylaxis dosing regimens? [abstract no. PB 1818]. Res Pract Thromb Haemost. 2017;1(Suppl 1):807–8.Google Scholar
  33. 33.
    Holme PA, Wang M, Saxena K, et al. Predictors of patients with 0 bleeds during every-7-days prophylaxis with BAY 94-9027 in PROTECT VIII [abstract no. PB 1780]. Res Pract Thromb Haemost. 2017;1(Suppl 1):786–7.Google Scholar
  34. 34.
    Santagostino E, Kerlin BA, Negrier C, et al. Characteristics of bleed-free patients on every-5-day dosing in the PROTECT VIII (BAY 94–9027) study [abstract]. Blood. 2018;132(Suppl 1):2486.Google Scholar
  35. 35.
    Linardi C, Enriquez MM, Lalezari S. BAY 94-9027 prophylaxis improves quality of life: Haemo-QoL-A data from the PROTECT VIII study [abstract no. W-P-010 (737)]. Haemophilia. 2018;24(Suppl 5):21–2.Google Scholar
  36. 36.
    Kerlin BA, Simpson ML, Reding MT, et al. Comparison of bleeding rates before and during BAY 94-9027 prophylaxis: data from the PROTECT VIII study and extension [abstract plus poster]. In: 4th Biennial Summit of the Thrombosis and Hemostasis Societies of North America. 2018.Google Scholar
  37. 37.
    Pabinger I, Oldenburg J, Huth-Kuhne A, et al. Prophylaxis with extended dosing of BAY 94-9027 decreases overall and joint bleeding rates with consistent consumption for over 4 years of treatment [abstract no. P09-5]. In: Annual Meeting of the Society of Thrombosis and Haemostasis Research. 2019.Google Scholar
  38. 38.
    Reding MT, Ng HJ, Tseneklidou-Stoefer D, et al. Safety of long-term prophylaxis with BAY 94-9027: interim results of >5 years of treatment in the PROTECT VIII extension trial [abstract no. W-P-001 (404)]. Haemophilia. 2018;24(Suppl 5):17–8.Google Scholar
  39. 39.
    Hanley J, McKernan A, Creagh MD, et al. Guidelines for the management of acute joint bleeds and chronic synovitis in haemophilia: a United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO) guideline. Haemophilia. 2017.
  40. 40.
    Schwartz CE, Powell VE, Su J, et al. The impact of extended half-life versus conventional factor product on hemophilia caregiver burden. Qual Life Res. 2018;27(5):1335–45.CrossRefGoogle Scholar
  41. 41.
    Baxalta US Inc. ADYNOVATE®: US prescribing information. 2016. Accessed 6 June 2019.
  42. 42.
    European Medicines Agency. Rurioctocog alfa pegol (Adynovi®): EU summary of product characteristics. 2019. Accessed 6 June 2019.
  43. 43.
    Novo Nordisk Inc. ESPEROCT® [antihemophilic factor (recombinant), glycopegylated-exei]: US prescribing information. 2019. Accessed 6 June 2019.
  44. 44.
    Ayyagari R, Deschaseaux C, Vashi PB, et al. Matching-adjusted indirect comparisons (MAICs) of efficacy and consumption of bay 94-9027 versus three recombinant factor VIII (rFVIII) for prophylaxis of severe hemophilia A [abstract no. PSY12]. Value Health. 2018;21(Suppl 1):S246.CrossRefGoogle Scholar
  45. 45.
    Shah A, Solms A, Wiegmann S, et al. BAY 94-9027 and recombinant factor VIII Fc fusion protein: a head-to-head, randomized, crossover, pharmacokinetic study in patients with severe haemophilia A [abstract no. P020]. Haemophilia. 2019;25(Suppl 1):45.Google Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Springer NatureAucklandNew Zealand

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