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Eftrenonacog Alfa: A Review in Haemophilia B

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Abstract

Eftrenonacog alfa (Alprolix™) is a recombinant fusion protein comprising human factor IX (FIX) covalently linked to the constant region (Fc) domain of human IgG1 (i.e. rFIXFc). The presence of the Fc domain extends the terminal half-life (t½) of rFIXFc, permitting prolonged treatment intervals. rFIXFc is available for intravenous use for the prophylaxis and treatment of bleeding in patients with haemophilia B. In two multinational, phase III studies in previously treated children, adolescents and adults with severe haemophilia B, rFIXFc prophylaxis resulted in low median annualized bleeding rates (ABRs), and was associated with reductions in median weekly factor consumption and dosing frequency compared with pre-study FIX regimens. Preliminary data from an extension of both studies indicated sustained efficacy, as demonstrated by low median ABRs, with longer-term rFIXFc prophylaxis. rFIXFc was also effective in the treatment of bleeding episodes and when used in the perioperative setting in all age groups. rFIXFc was well tolerated in clinical studies in previously treated patients, with the majority of treatment-emergent adverse events considered to be unrelated to rFIXFc; there were no reports of inhibitor development. In conclusion, rFIXFc provides an effective alternative to plasma-derived and recombinant FIX products for the management of patients with haemophilia B, with its extended t½ permitting a less frequent administration schedule and potentially providing a prolonged protective haemostatic effect, which eases the treatment burden on the patient.

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References

  1. Peyvandi F, Garagiola I, Biguzzi E. Advances in the treatment of bleeding disorders. J Thromb Haemost. 2016;14(11):2095–106.

    Article  CAS  PubMed  Google Scholar 

  2. Makris M. Prophylaxis in haemophilia should be life-long. Blood Transfus. 2012;10(2):165–8.

    PubMed  PubMed Central  Google Scholar 

  3. Nazeef M, Sheehan JP. New developments in the management of moderate-to-severe hemophilia B. J Blood Med. 2016;7:27–38.

    PubMed  PubMed Central  Google Scholar 

  4. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1–47.

    Article  CAS  PubMed  Google Scholar 

  5. Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016;388(10040):187–97.

    Article  PubMed  Google Scholar 

  6. Sobi. ALPROLIX (eftrenonacog alfa): EU summary of product characteristics. 2016. http://www.ema.europa.eu/. Accessed 19 May 2017.

  7. Biogen Idec Inc. ALPROLIX™ [coagulation factor IX (recombinant), Fc fusion protein]: US prescribing information. 2014. http://www.fda.gov/. Accessed 19 May 2017.

  8. Rath T, Baker K, Dumont JA, et al. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol. 2015;35(2):235–54.

    Article  CAS  PubMed  Google Scholar 

  9. Peters RT, Low SC, Kamphaus GD, et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood. 2010;115(10):2057–64.

    Article  CAS  PubMed  Google Scholar 

  10. McCue J, Osborne D, Dumont J, et al. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein. Haemophilia. 2014;20(4):e327–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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(24):2313–23.

    Article  CAS  PubMed  Google Scholar 

  12. 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 Haematology. 2017;4(2):e75–82.

    Article  PubMed  Google Scholar 

  13. European Medicines Agency. Alprolix (eftrenonacog alfa): EU assessment report. 2016. http://www.ema.europa.eu/. Accessed 19 May 2017.

  14. 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(3):666–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. US FDA. Recombinant coagulation factor IX Fc fusion protein (rFIXFc, ALPROLIX™): clinical pharmacology BLA review. 2013. http://www.fda.gov/. Accessed 19 May 2017.

  16. 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 Pharmacokinet. 2014;53(5):467–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shima M, Fukutake K, Hanabusa H, et al. Japanese subject subpopulation analysis of B-LONG: a Phase 3 study of long-acting recombinant factor IX Fc fusion protein. Jpn J Thromb Hemost. 2015;26(4):420–9.

    Article  Google Scholar 

  18. Pasi KJ, Fischer K, Ragni M, et al. Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B. Thromb Haemost. 2017;117(3):508–18.

    Article  PubMed  Google Scholar 

  19. Mahlangu JN, Shapiro AD, Pasi KJ, et al. Individualised prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in adults/adolescents with haemophilia B: updated interim results of the B-YOND extension study [abstract no. P094 plus poster]. Haemophilia. 2017;23(Suppl 2):85.

    Google Scholar 

  20. Matsushita T, Mahlangu J, Shapiro AD. Clinical outcomes in adults/adolescents with hemophilia B treated long term with recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis: interim results of the B-YOND extension study [abstract no. 1416]. In: 58th Annual Meeting of ASH. 2016.

  21. Ducore JM, Fischer K, Kulkarni R, et al. Long term safety and efficacy of recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis in children with hemophilia B: interim results of the B-YOND extension study [abstract]. Blood. 2016;128(22):4976.

    Google Scholar 

  22. Fischer K, Kulkarni R, Nolan B, et al. Individualised prophylaxis in children with haemophilia B treated long term with recombinant factor IX Fc fusion protein (rFIXFc): updated interim results of the B-YOND extension study [abstract no. P108 plus poster]. Haemophilia. 2017;23(Suppl 2):94.

    Google Scholar 

  23. Shapiro AD, Perry DJ, Baker RI. Analysis of target joint bleeding with prophylactic use of recombinant factor IX Fc fusion protein in patients with severe hemophilia B [abstract]. Blood. 2015;126(23):2294.

    Google Scholar 

  24. Shapiro AD, Kulkarni R, Windyga J, et al. Increase or maintenance of physical activity in patients treated with recombinant factor IX Fc fusion protein (rFIXFc) in the B-LONG and Kids B-LONG studies [abstract no. CRCT11]. In: 67th Annual Meeting of NHF. 2015.

  25. Kulkarni R, Shapiro AD, Windyga J, et al. Low bleeding rates with increase or maintenance of physical activity in patients treated with recombinant factor IX Fc fusion protein (rFIXFc) in the B-LONG and Kids B-LONG studies [abstract]. Blood. 2015;126(23):2307.

    Google Scholar 

  26. Powell J, Shapiro A, Ragni M, et al. Switching to recombinant factor IX Fc fusion protein prophylaxis results in fewer infusions, decreased factor IX consumption and lower bleeding rates. Br J Haematol. 2015;168(1):113–23.

    Article  CAS  PubMed  Google Scholar 

  27. Shapiro AD, Kulkarni R, Ozelo M, et al. Analysis of annualized bleeding rates and baseline characteristics in subjects with a 14-day or longer dosing interval in the phase 3 B-long study of recombinant factor IX Fc fusion protein [abstract plus poster]. Am J Hematol. 2016;91(9):E406.

    Google Scholar 

  28. Wyrwich KW, Krishnan S, Auguste P, et al. Changes in health-related quality of life with treatment of longer-acting clotting factors: results in the A-LONG and B-LONG clinical studies. Haemophilia. 2016;22(6):866–72.

    Article  CAS  PubMed  Google Scholar 

  29. Kulkarni R, Pasi KJ, Liesner R, et al. Post hoc analysis to evaluate the effect of recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis in adults and adolescents with target joints and hemophilia B [abstract]. Haemophilia. 2016;22(Suppl 4):44.

    Google Scholar 

  30. Powell JS, Apte S, Chambost H, et al. Long-acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B-LONG study. Br J Haematol. 2015;168(1):124–34.

    Article  CAS  PubMed  Google Scholar 

  31. Ozelo MC, Mahlangu J, Chan G, et al. Perioperative management of hemostasis with recombinant FIX Fc fusion protein in subjects undergoing surgery in the B-YOND study [abstract]. Blood. 2015;126(23):1083.

    Google Scholar 

  32. Biogen Canada Inc. ALPROLIX® [coagulation factor IX (recombinant), Fc fusion protein]: Canadian product monograph. 2016. http://www.hc-sc.gc.ca/. Accessed 19 May 2017.

  33. Pharmaceuticals and Medical Devices Agency. Alprolix for intravenous injection: Japanese prescribing information. 2017. http://www.pmda.go.jp/. Accessed 20 Mar 2017.

  34. Nolan B, Pipe S, Manco-Johnson M, et al. Study design of a phase 3, open-label trial of the safety and efficacy of recombinant factor IX Fc fusion protein for the prevention and treatment of bleeding episodes in previously untreated patients with severe hemophilia B [abstract no. 0050]. In: 66th Annual Meeting of NHF. 2014.

  35. CSL Behring GmbH. IDELVION (albutrepenonacog alfa): EU summary of product characteristics. 2016. http://www.ema.europa.eu/. Accessed 19 May 2017.

  36. CSL Behring LLC. IDELVION [coagulation factor IX (recombinant), albumin fusion protein]: US prescribing information. 2016. http://www.fda.gov/. Accessed 19 May 2017.

  37. CSL Behring Canada Inc. IDELVION™ [coagulation factor IX (recombinant), albumin fusion protein (rIX-FP)]: Canadian product monograph. 2017. http://www.hc-sc.gc.ca/. Accessed 19 May 2017.

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Acknowledgements

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

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  1. Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Sheridan M. Hoy

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  1. Sheridan M. Hoy
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Correspondence to Sheridan M. Hoy.

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Funding

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

Conflict of interest

Sheridan Hoy is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/E698F060304983F9.

Additional information

The manuscript was reviewed by: J. N. Mahlangu, Haemophilia Comprehensive Care Centre, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; M. E. Mancuso, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy; M. Morfini, Past President of Italian Association of Haemophilia (AICE), Florence, Italy.

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Hoy, S.M. Eftrenonacog Alfa: A Review in Haemophilia B. Drugs 77, 1235–1246 (2017). https://doi.org/10.1007/s40265-017-0778-1

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