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Brand Name
hylenex recombinant
Generic Name
Hyaluronidase human injection
Therapeutic Class
Tissue Permeability Modifier
Pharmacology
Hyaluronidase is a spreading or diffusing enzyme that increases the permeability of connective tissue through the hydrolysis of hyaluronan (hyaluronic acid), a polysaccharide found in the intercellular matrix of connective tissue. Hyaluronan acts as a barrier to drug and fluid dispersion. Hyaluronidase hydrolyzes hyaluronan by splitting the glucosaminidic bond between C1 of an N-acetylglucosamine moiety and C4 of a glucuronic acid moiety. The hydrolysis of hyaluronan temporarily decreases the viscosity of the intercellular matrix and promotes diffusion of injected fluids or of localized transudates or exudates.1
Hyaluronidase increases dispersion in the interstitial matrix provided local pressure is adequate to furnish the necessary mechanical impulse. Such impulse is normally initiated by injected solutions. The rate of diffusion is proportionate to the amount of enzyme. The extent of diffusion is proportionate to the volume of solution.
At 24 hours, the restoration of the hyaluronan barrier is incomplete and inversely related to the dosage of the enzyme. At 48 hours, the barrier is completely restored.
The protein is inactivated and metabolized within minutes when it enters the bloodstream.1
Allergenicity Trial2
Assessment and Implication of the Allergic Sensitivity to a Single Dose of Recombinant Human Hyaluronidase (rHuPH20) Injection
In support of FDA approval, an allergenicity trial with 100 healthy volunteers was conducted to evaluate the sensitivity of healthy volunteer subjects to a single dose of recombinant human hyaluronidase (hylenex recombinant). Subjects were injected with 0.1 ml (15U) of the hylenex recombinant intradermally in the volar forearm and with 0.1 ml of 0.9% sodium chloride injection USP (saline) in the contralateral forearm (control arm). The injection sites were evaluated at approximately 1-minute intervals for the first 5 minutes after injection and then at 30 minutes after injection. The subjects were followed-up by telephone or a visit at 24 hours after injection. 100 subjects (75 women and 25 men) of mean age 37 years (range, 18-70 years) were enrolled in the study. All 100 subjects received both treatments and completed all of the scheduled evaluations.
Incidence of observations within 5 minutes after injection
| Observation |
hylenex recombinant
(N=100) |
Saline Placebo
(N=100) |
| Allergic Reaction* |
0% |
0% |
Any observation
within 5 minutes |
78% |
84% |
| Wheal |
32% |
30% |
| Pseudopods |
0% |
0% |
| Localized Itching |
2% |
8% |
*Occurrence of a wheal with pseudopods within 5 minutes of injection that persisted for at least 20 minutes and that was accompanied by localized itching
At 5 minutes after injection:
- The incidence of wheal was comparable for hylenex recombinant and saline.
- The incidence of itching was 4 times higher for saline than for hylenex recombinant.
- No pseudopods were observed with either treatment.
Incidence of observations within 30 minutes of injection
Click Graph to Enlarge
At 30 minutes after injection:
- The incidences of erythema and wheal were comparable for hylenex recombinant and saline.
- The incidence of ecchymosis and localized itching were higher for saline than for hylenex recombinant.
- The incidence of any symptom of discomfort was significantly higher for saline than for hylenex recombinant.
Incidence of observations at 48 hours after injection
| Observation |
hylenex recombinant
(N=100) |
Saline Placebo
(N=100) |
| Any Observation* |
65% |
27% |
| Ecchymosis |
62% |
27% |
| Discoloration |
3% |
0% |
| Erythema |
1% |
0% |
| Bruising |
1% |
0% |
*Subjects may have had more than 1 symptom per forearm.
At 48 hours after injection:
- The incidence of any injection site observation was higher for hylenex recombinant than for saline primarily caused by a higher incidence of ecchymosis at injection sites.
Click here to see full article.
INFUSE (INcreased Flow Utilizing Subcutaneously-Enabled)
Clinical Trial3
Subsequent to the Allergenicity Trial, Baxter Healthcare Corporation and Halozyme Therapeutics, Inc. initiated the INFUSE clinical trial program to further evaluate the efficacy and safety of hylenex recombinant.
INFUSE-LR:
This randomized, double-blind, placebo-controlled, within-subject trial was performed to compare flow rate, tolerability, and safety of gravity-driven subcutaneous fluid administration with and without recombinant human hyaluronidase (hylenex recombinant) in 54 healthy volunteers.
24–gauge angiocatheters were placed subcutaneously in both upper arms. Each arm received hylenex recombinant (150 U, 750 U, or 1500 U) or equal volume saline placebo. Immediately, 400 mL Lactated Ringer's (LR) solution was gravity-infused from a 100 cm height. In the pilot stage, 5 subjects also received a similar intravenous infusion.
Recommended dosing for subcutaneous hydration is 150 Units to facilitate the absorption of 1000 mL or more of solution.
Mean flow rates for subcutaneously administered infusion of Lactated Ringer's
Click Graph to Enlarge
- hylenex recombinant 150 U, 750 U, and 1500 U yielded mean flow rates of 383±119 mL/hr, 518±154 mL/hr, and 494±136 mL/hr, respectively, compared to their respective placebo rates of 82±30 mL/hr, 148±57 mL/hr, and 124±50 mL/hr.
Edema in a representative subject’s arm during infusion
Incidence of moderate and severe edema
Click Graph to Enlarge
- At all hylenex recombinant doses and all time points during infusions, hyaluronidase arms yielded significantly less edema.
Time to recovery to baseline arm circumference
Click Graph to Enlarge
- Each hylenex recombinant dose led to a statistically significant decrease in time to baseline circumference.
Click here to see full article.
Clinical Trial*
INFUSE-Pediatric Rehydration Study: Phase IV Study of Subcutaneous Rehydration With Recombinant Human Hyaluronidase (hylenex recombinant) for Infants and Children
Purpose: The aim of the study is to evaluate the safety, effectiveness and ease of use of subcutaneous rehydration using hylenex recombinant-augmented subcutaneous infusion of fluids and electrolytes for the rehydration of pediatric patients with mild to moderate dehydration.
Study Type: Interventional
Enrollment: 51
Study Design: Treatment, non-randomized, open label, uncontrolled, single group assignment, safety/efficacy study
Primary Outcome Measures:
- Rehydration success rate (effectiveness) in children treated with hylenex recombinant-augmented fluid infusion
Secondary Outcome Measures:
- Safety of hylenex recombinant-augmented fluid infusion in children
*Publication pending.
Click here to see full Prescribing Information and Important Safety Information.
References: 1. Data on file. Halozyme Therapeutics, Inc. 2. Yocum RC, Kennard D, Heiner LS. Assessment and implication of the allergic sensitivity to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-controlled clinical trial. J Infus Nurs. 2007;30:293-299. 3. Thomas JR, Yocum RC, Haller MF, von Gunten CF. Assessing the role of human recombinant hyaluronidase in gravity-driven subcutaneous hydration: The INFUSE-LR study. J Palliat Med. 2007;10:1312-1320.
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