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Human Immunoglobulin 10 % with Recombinant Human Hyaluronidase: Replacement Therapy in Patients with Primary Immunodeficiency Disorders

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Abstract

Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.

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References

  1. Boyle JM, Buckley RH. Population prevalence of diagnosed immunodeficiency diseases in the United States. J Clin Immunol. 2007;27(5):497–502.

    Article  CAS  PubMed  Google Scholar 

  2. Eley B. An update of the primary antibody disorders. Curr Allergy Clin Immunol. 2008;21(1):13–9.

    Google Scholar 

  3. Wasserman RL. Progress in gamma globulin therapy for immunodeficiency: from subcutaneous to intravenous infusions and back again. J Clin Immunol. 2012;32(6):1153–64.

    Article  CAS  PubMed  Google Scholar 

  4. McCormack PL. Immune globulin subcutaneous (human) 20 %: in primary immunodeficiency disorders. Drugs. 2012;72:1087–97.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. McCormack PL. Immune globulin (human) 10 % liquid: a review of its use in primary immunodeficiency disorders. Biodrugs. 2013;27(4):303–400.

    Article  Google Scholar 

  6. Lucas M, Lee M, Lortan J, et al. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol. 2010;125(6):1354–60.

    Article  CAS  PubMed  Google Scholar 

  7. Jolles S, Sewell WAC, Misbah SA. Clinical uses of intravenous immunoglobulin. Clin Exp Immunol. 2005;142(1):1–11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Wasserman RL. Overview of recombinant human hyaluronidase-facilitated subcutaneous infusion of IgG in primary immunodeficiencies. Immunotherapy. 2014;6(5):553–67.

    Article  CAS  PubMed  Google Scholar 

  9. Bookbinder LH, Hofer A, Haller MF, et al. A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release. 2006;114(2):230–41.

    Article  CAS  PubMed  Google Scholar 

  10. Baxter Healthcare. HyQvia (human normal immunoglobulin with recombinant human hyaluronidase) 100 mg/mL solution for infusion for subcutaneous use: summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002491/WC500143851.pdf. Accessed 5 June 2014.

  11. Baxter Healthcare. Gammagard Liquid [immune globulin infusion (human)] 10 %: US prescribing information. 2013. http://www.baxter.com/products/biopharmaceuticals/downloads/gamliquid_PI.pdf. Accessed 5 June 2014.

  12. Spandorfer PR, Mace SE, Okada PJ, et al. A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department. Clin Ther. 2012;34(11):2232–45.

    Article  CAS  PubMed  Google Scholar 

  13. Muchmore DB, Vaughn DE. Accelerating and improving the consistency of rapid-acting analog insulin absorption and action for both subcutaneous injection and continuous subcutaneous infusion using recombinant human hyaluronidase. J Diabetes Sci Tech. 2012;6(4):764–72.

    Article  Google Scholar 

  14. Shpilberg O, Jackisch C. Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase. Br J Cancer. 2013;109(6):1556–61.

    Article  CAS  PubMed  Google Scholar 

  15. Misbah S, Sturzenegger MH, Borte M, et al. Subcutaneous immunoglobulin: opportunities and outlook. Clin Exp Immunol. 2009;158(Suppl 1):51–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Rosengren S, Huang L, Wei G, et al. Characterization of antibodies reactive with recombinant human hyaluronidase (rHuPH20) from treatment naive plasma donors and PID subjects treated with IGHy [abstract]. 2014 Clinical Immunology Society Annual Meeting; 10–13 April 2014; Baltimore (MD).

  17. Melamed I, Wasserman RL, Stein M, et al. Long-term tolerability and safety of facilitated-subcutaneous infusion of human immunoglobulin G, 10 %, and recombinant human hyaluronidase: a phase 3 extension study in patients with primary immunodeficiencies [abstract no. 621]. J Allergy Clin Immunol. 2014;132(2):AB180. Plus poster presented at the Annual Meeting of the American Academy of Allergy, Asthma, and Immunology 28 February-4 March 2014, San Diego, CA.

  18. Wasserman RL, Melamed I, Stein MR, et al. Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. J Allergy Clin Immunol. 2012;130(4):951–7.e11.

  19. European Medicines Agency. Committee for Medicinal Products for Human Use assessment report HyQvia (human normal immunoglobulin). 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002491/WC500143854.pdf. Accessed 5 June 2014.

  20. Stein M, Wasserman RL, Melamed I, et al. Tolerability/efficacy/pharmacokinetics of facilitated-subcutaneous infusion of human immune globulin G, 10 %, and recombinant human hyaluronidase in adults with primary immunodeficiency: phase III study [abstract]. International Primary Immunodeficiencies Congress 2013; 7–8 November, 2013; Lisbon.

  21. Wasserman RL, Melamed I, Stein M, et al. Tolerability and efficacy of facilitated-subcutaneous infusion of immune globulin (human), 10 % and recombinant human hyaluronidase (IGHy) in a subset of study patients with primary immunodeficiency disease (PIDD) [abstract no. 56]. J Allergy Clin Immunol. 2012;129(2):AB15.

  22. Iyer R, Luo M, Li-McLeod J. Modeled economic impact of facilitated-subcutaneous infusion of immune globulin (human), 10 % with recombinant human hyaluronidase (IGHy) or intravenous immunoglobulin (IGIV) in primary immunodeficiency (PI) patients [abstract]. J Clin Immunol. 2012;32:397.

    Google Scholar 

  23. Tamma P. Vaccines in immunocompromised patients. Pediatr Rev. 2010;31(1):38–40.

    Article  PubMed  Google Scholar 

  24. Baxter International, Inc. Baxter confirms receipt of Complete Response Letter on HyQ [media release]. 1 Aug 2012. http://www.baxter.com/press_releases/2012/08_01_12_hyq.html.

  25. European Medicines Agency. Guideline on the clinical investigation of human normal immunoglobulin for subcutaneous and/or intramuscular administration (SCIg/IMIg) (draft). 2012. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/12/WC500135705.pdf. Accessed 5 June 2014.

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Disclosure

The preparation of this review was not supported by any external funding. Mark Sanford is a salaried employee of Adis/Springer. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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  1. Adis, Level 1, 5 The Warehouse Way, Northcote 0627; Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Mark Sanford

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  1. Mark Sanford
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Correspondence to Mark Sanford.

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The manuscript was reviewed by: P. Atkinson, Division of Pediatric Allergy and Immunology, University of Alabama at Birmingham, Birmingham, AL, USA; A. Fasth, Department of Pediatrics, The Queen Silvia Children’s Hospital and University of Gothenburg, Gothenburg, Sweden; W.A.C. Sewell, Department of Immunology, Scunthorpe General Hospital and University of Lincoln, Scunthorpe, UK; R.S. Shapiro, Midwest Immunology Clinic and Infusion Center, Minneapolis, MN, USA.

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Sanford, M. Human Immunoglobulin 10 % with Recombinant Human Hyaluronidase: Replacement Therapy in Patients with Primary Immunodeficiency Disorders. BioDrugs 28, 411–420 (2014). https://doi.org/10.1007/s40259-014-0104-3

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