Efficacy, Safety, and Pharmacokinetics of a 10% Liquid Immune Globulin Preparation (GAMMAGARD LIQUID, 10%) Administered Subcutaneously in Subjects with Primary Immunodeficiency Disease

Wasserman, Richard L.; Melamed, Isaac; Kobrynski, Lisa; Strausbaugh, Steven; Stein, Mark R.; Sharkhawy, Marlies; Engl, Werner; Leibl, Heinz; Sobolevsky, Luba; Gelmont, David; Schiff, Richard I.; Grossman, William

doi:10.1007/s10875-011-9512-z

Cited by 71 publications

(95 citation statements)

References 22 publications

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“…In summary, SCIG clinical trials have shown relatively high IgG trough levels when compared with IVIG in the same study (Wasserman , 2011.…”

Section: Subcutaneous Immunoglobulin Therapymentioning

confidence: 66%

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The history and evolution of immunoglobulin products and their clinical indications

Hooper¹

2015

LymphoSign Journal

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The history of providing antibodies to treat diseases began in the 19th century with the discovery of tetanus and diphtheria toxins and the demonstration that immunity to tetanus and diphtheria infections could be transferred by immune sera. Characterization of the mediators of this immunity resulted in the discovery that antibodies are proteins that can be isolated and used to protect against infectious diseases. Development of a method to isolate antibodies from human plasma that could be safely injected into people initiated the development of human gamma globulin preparations to provide antibodies to patients with inherited antibody deficiencies. To overcome the limitations imposed by intramuscular injection of gamma globulin, intravenous gamma globulin preparations were developed that began to be used in a wide variety of clinical conditions. Thus the original clinical indication for infection prevention was expanded to several other indications that employ large doses to suppress inflammatory and autoimmune disorders. The most recent development in immunoglobulin therapy is the production of concentrated immune globulins for subcutaneous injection. Home infusions of subcutaneous immunoglobulin are increasingly used to treat immunodeficient patients and are being studied for other clinical applications.

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“…In summary, SCIG clinical trials have shown relatively high IgG trough levels when compared with IVIG in the same study (Wasserman , 2011.…”

Section: Subcutaneous Immunoglobulin Therapymentioning

confidence: 66%

“…Subcutaneous administration of Gammagard Liquid was also studied in an open-label trial of 49 patients with PID (Wasserman et al 2011). All subjects received IV infusions of Gammagard Liquid for 13 weeks.…”

Section: Subcutaneous Immunoglobulin Therapymentioning

confidence: 99%

The history and evolution of immunoglobulin products and their clinical indications

Hooper¹

2015

LymphoSign Journal

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“…In this study, 87 adults and children 4-78 years of age with PIDD received IVIG every 3 or 4 weeks for 3 months, and 83 patients were then treated with IGHy for approximately 14-18 months. Of the 83 patients, 31 received 3 months of IVIG followed by 12 months of conventional SCIG without rHuPH20 in a previous study (NCT00546871) [38] and then were enrolled to receive IGHy for 14-18 months in the Phase III study [16]. All patients received IGHy at the same dose and frequency as their prestudy IVIG.…”

Section: Phase III and Extension Studies Study Design And Patientsmentioning

confidence: 99%

Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Wasserman

2017

Immunotherapy

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Most primary immunodeficiency diseases (PIDDs) resulting in antibody deficiency require intravenous or subcutaneous immunoglobulin G (SCIG) replacement therapy. The flow and distribution of SCIG to the vasculature is impeded by the glycosaminoglycan hyaluronan in the extracellular matrix, which limits the infusion rate and volume per site, necessitating frequent infusions and multiple infusion sites. Hyaluronidase depolymerizes hyaluronan and is a spreading factor for injectable biologics. Recombinant human hyaluronidase (rHuPH20) increases SCIG absorption and dispersion. In patients with PIDD, SCIG facilitated with rHuPH20 (IGHy) has been shown to prevent infections, be well-tolerated and reduce infusion frequency and number of infusion sites as compared with conventional SCIG. This article reviews IGHy clinical studies and real-world practice data in patients with PIDD.

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“…Adjusting the dose to achieve the same AUC is considered necessary because of presumed differences in the bioavailability of IgG and similar proteins when given by the intramuscular (IM) or subcutaneous (SC) routes as compared with the intravenous (IV) route [2]. Dose adjustments of 120 % to 153 % have been used in different studies of polyclonal SCIG, implying that the different products have different bioavailabilities [3][4][5][6]. However, "non-inferiority" designs, which accept a margin of ±20 % of AUC, have been employed, so the derived dose adjustments may not reflect the actual bioavailability of different products [1].…”

Section: Introductionmentioning

confidence: 99%

Bioavailability of IgG Administered by the Subcutaneous Route

Berger¹,

Jolles²,

Sleasman³

2012

Journal of Allergy and Clinical Immunology

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Purpose US licensing studies of subcutaneous IgG (SCIG) calculate dose adjustments necessary to achieve area under the curve (AUC) of serum IgG vs. time on SCIG that is noninferior to that on intravenous IgG (IVIG), within the FDAset limit of ±20 %. The results are interpreted as showing that different SCIGs differ in bioavailability. We used three approaches to determine if the bioavailabilities were actually different. Methods Dose adjustments and AUCs from published licensing studies were used to calculate bioavailabilities using the formula: Bioavailability (% of IVIG) = AUC(SCIG) ÷ AUC(IVIG) x 1/Dose Adjustment. We also compared the increment in serum IgG concentration achieved with varying doses of SCIG in recent meta-analyses with the increment with different doses of IVIG, and determined the serum IgG concentrations when patients switched SCIG products at the same dose. Results The actual bioavailabilities were: Gamunex® 65.0 %, Hizentra® 65.5 %, Gammagard® 67.2 %, Vivaglobin® 69.0 %. Regression analyses of serum IgG vs. dose showed that the mean increase in serum IgG resulting from a 100 mg/kg/month increment in SCIG dosing was 69.4 % of the increase with the same increment in IVIG dosing (84 mg/dL vs. 121 mg/dL). Patients switching SCIG preparations at the same dose had no change in serum IgG levels, confirming that bioavailabilities of the SCIG preparations did not differ.Conclusions Decreased bioavailability appears to be a basic property of SCIG and not a result of any manufacturing process or concentration. Because serum IgG levels do not vary with different SCIG products at the same dose, adjustments are not necessary when switching products.

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Efficacy, Safety, and Pharmacokinetics of a 10% Liquid Immune Globulin Preparation (GAMMAGARD LIQUID, 10%) Administered Subcutaneously in Subjects with Primary Immunodeficiency Disease

Cited by 71 publications

References 22 publications

The history and evolution of immunoglobulin products and their clinical indications

The history and evolution of immunoglobulin products and their clinical indications

Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Bioavailability of IgG Administered by the Subcutaneous Route

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