Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency

Wasserman, Richard L.; Melamed, Isaac; Stein, Mark R.; Gupta, Sudhir; Puck, Jennifer M.; Engl, Werner; Leibl, Heinz; McCoy, Barbara; Empson, Victoria; Gelmont, David; Schiff, Richard I.

doi:10.1016/j.jaci.2012.06.021

Cited by 112 publications

(144 citation statements)

References 31 publications

(43 reference statements)

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“…The primary end point was the annual rate of acute serious bacterial infections [16]. 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.…”

Section: Phase III and Extension Studies Study Design And Patientsmentioning

confidence: 99%

“…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%

“…All patients received IGHy at the same dose and frequency as their prestudy IVIG. Patients received rHuPH20 at a dose of 75 U/g IgG administered through a 24-gauge high-flow subcutaneous needle followed by IgG 10% at 108% of the weekly IVIG equivalent dose, using the same subcutaneous needle and infusion line [16]. The 108% dose of IgG was based on the finding from the Phase I/II study that the bioavailability of IGHy was 92% of the IVIG dose [37].…”

Section: Phase III and Extension Studies Study Design And Patientsmentioning

confidence: 99%

“…One strategy that effectively overcomes many of the limitations of conventional SCIG involves preceding the subcutaneous infusion of IgG with an infusion of hyaluronidase, an enzyme that catalyzes depolymerization of hyaluronan, resulting in enhanced drug delivery by increasing dispersion and absorption of IgG from the subcutaneous tissues, allowing larger volumes to be infused in each infusion site [16]. Recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous infusion of IgG (IGHy) is commercially available as HyQvia (Baxalta US, Inc., CA, USA, now part of Shire).…”

mentioning

confidence: 99%

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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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Section: Phase III and Extension Studies Study Design And Patientsmentioning

confidence: 99%

Section: Phase III and Extension Studies Study Design And Patientsmentioning

confidence: 99%

Section: Phase III and Extension Studies Study Design And Patientsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Wasserman

2017

Immunotherapy

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“…Subcutaneous infusion is now a frequently selected infusion route used for opioid drugs in hospitals (Herndon & Fike, 2001;Justad, 2009), and it is also an effective way in treating diabetes (Hirsch et al, 2005;Fujikawa et al, 2012), cancer (Leahy et al, 1992;Befon et al, 2000), bacterial infections (Champoux et al, 1996), gastrointestinal obstruction (De Conno et al, 1991) and primary immunodeficiency deficiencies (Kirmse 2009;Wasserman et al, 2012). Such administration way, allowing patients to manage their own infusions at home, is also very suitable for ambulatory outpatients.…”

Section: Introductionmentioning

confidence: 99%

The development and evaluation of a subcutaneous infusion delivery system based on osmotic pump control and gas drive

Xie

Yang²,

Yang³

et al. 2014

Drug Delivery

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(2016) The development and evaluation of a subcutaneous infusion delivery system based on osmotic pump control and gas drive, Drug Delivery, 23:7, 2193-2204, DOI: 10.3109/10717544.2014 AbstractA novel, self-administration drug delivery system for subcutaneous infusion was developed and evaluated. The device includes two main components: an osmotic tablet controlled gas actuator and a syringe catheter system. The sodium carbonate in the osmotic pump tablet will release into the surround citric acid solution and produce CO 2 gas, which will drive the drug solution into subcutaneous tissue. The key formulation factors of the osmotic tablet that would influence the infusion profiles of the device were investigated by single factor exploration. The formulation was optimized via a response surface methodology. With an 18 ± 4 min of lag time, the delivery system was able to infuse at an approximate zero-order up to 5.90 ± 0.37 h with a precision of 9.0% RSD (n ¼ 6). A linear correlation was found for the infusion profile and the fitting equation was Y ¼ 0.014X À 0.004 (r ¼ 0.998). A temperature change of 4 C was found to modify the flow rate by about 12.0%. In vivo results demonstrated that the present subcutaneous infusion device was similar to the commercial infusion pump, and it could bring a long and constant ampicillin plasma level with minimized fluctuations.

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Safety, Tolerability, and Pharmacokinetics of High‐Volume Subcutaneous Crenezumab, With and Without Recombinant Human Hyaluronidase in Healthy Volunteers

Dolton¹,

Chesterman²,

Moein³

et al. 2021

Clin Pharma and Therapeutics

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Compared with intravenous formulations, subcutaneous (s.c.) formulations of therapeutic monoclonal antibodies may provide increased patient access and more convenient administration options, although historically highvolume s.c. administration (> 10-15 mL) has been challenging. We report results from two phase I studies in healthy participants (GP29523 and GP40201) that evaluated s.c. crenezumab, an anti-Aβ monoclonal antibody in development for individuals at risk for autosomal-dominant Alzheimer's disease. GP29523 assessed safety, tolerability, and pharmacokinetics (PK) in 68 participants (aged 50-80 years) who received single ascending doses (600-7,200 mg) of crenezumab or placebo (4-40 mL). GP40201 assessed safety, tolerability, and PK in 72 participants (aged 18-80 years) who received different combinations of dose (1,700-6,800 mg), infusion volume (10-40 mL), and flow rate (2-4 mL/minute), with/without recombinant human hyaluronidase (rHuPH20). There were no serious or dose-limiting adverse events in either study. There were no meaningful differences in pain scores among reference placebo (4 mL), test placebo (4-40 mL), or crenezumab (600-7,200 mg) in GP29523, or across treatments with varying infusion volume, flow rate, dose, or rHuPH20 co-administration or concentration in GP40201. Transient erythema was the most common infusion site reaction in both studies. In GP40201 at volumes of ≥ 20 mL, rHuPH20 co-administration appeared to reduce infusion site swelling incidence, but, in some cases, was associated with larger areas of infusion site erythema. Crenezumab exhibited approximately doseproportional PK, and s.c. bioavailability was 66% and independent of dose or rHuPH20 co-administration. High-dose, high-concentration, high-volume s.c. crenezumab formulated with/without rHuPH20 was well-tolerated in healthy participants, with an acceptable safety profile.

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Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency

Cited by 112 publications

References 31 publications

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

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

The development and evaluation of a subcutaneous infusion delivery system based on osmotic pump control and gas drive

Safety, Tolerability, and Pharmacokinetics of High‐Volume Subcutaneous Crenezumab, With and Without Recombinant Human Hyaluronidase in Healthy Volunteers

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