Pre-administration of rHuPH20 prior to insulin infusion provides consistent ultrafast absorption and superior post-meal glucose control
SAN DIEGO, Oct. 27, 2011 -- /PRNewswire/ -- Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the diabetes, cancer, dermatology and drug delivery markets, today announced positive results from a study in patients with type 1 diabetes that receive their insulin therapy via pumps. The Phase 1b study was conducted as a randomized, double-blind, crossover design, to determine insulin pharmacokinetics, glucodynamics, safety and tolerability of rHuPH20 (recombinant human hyaluronidase) as a single injection prior to the start of three days of NovoLog® insulin aspart pump infusion therapy. The data demonstrated that pre-administration of 150 units of rHuPH20 (approximately 1.3 micrograms of enzyme) led to consistent insulin exposure over the infusion set life and superior glucose control following meals.
"The more consistent physiologic insulin absorption profiles observed over infusion set life in these studies are promising," said Daniel Einhorn, MD, FACP, FACE, Clinical Professor of Medicine at the University of California, San Diego and Medical Director of the Scripps Whittier Diabetes Institute. "Reducing the variability of insulin absorption should provide patients on insulin pump therapy improved ability to control diabetes while reducing risks of hypoglycemia."
Clinical Study and Results
The study compared pharmacokinetic (PK) and glucodynamic (GD) responses during euglycemic glucose clamp studies and responses to standardized mixed meal challenges administered in conjunction with individualized doses of insulin aspart, throughout the infusion set use with and without a single injection of rHuPH20 through the catheter set. The study also evaluated safety and local tolerability of rHuPH20 over the course of 72 hours of inpatient pump delivery, following pre-administration of rHuPH20 through subcutaneous infusion.
Compared to insulin aspart alone, pre-administration with rHuPH20 reduced the variability in insulin exposure and action profiles observed with continuous insulin infusion and provided a consistent ultrafast profile over 3 days of use.
- Consistent with previous reports, rapid acting analog insulin delivered by itself via subcutaneous infusion exhibited significant variability in both absorption and action over three days of infusion set use. From beginning to end of three days of infusion, early insulin exposure varied from 15 to 27% (p=.0004), onset of action varied from 60 min to 30 min (p<.0001), and duration of action varied from 180 to 156 minutes (p<.0001).
- rHuPH20 pre-administration eliminated this variability in absorption over three days of infusion set use. Fractional early insulin exposure at the beginning and end of infusion set use was 31% and 32%, respectively (p=.76), with corresponding values for onset of action at 34 and 32 min (p=.73), and duration of action at 139 and 146 minutes (p=.28)
- rHuPH20 pre-administration also accelerated insulin absorption resulting in 57% more early insulin exposure (p<.0001) and a 27 minute shorter duration of action (p<.0001).
In the test meal setting, the consistent ultrafast profile with pre-administration of rHuPH20 led to consistently reduced postprandial excursions.
- Reduction in 2 hour glycemic excursions (21 mg/dL) was significant (p=.017).
- Better achievement of American Association of Clinical Endocrinologists (AACE) target; p=.035 (7 of 15 subjects with rHuPH20 pre-treatment versus 3 of 15 subjects without rHuPH20 were able to achieve target at all 3 dinner meals tested).
Insulin aspart infusion with and without rHuPH20 pretreatment was similarly well tolerated.
Halozyme Therapeutics is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the insulin, cancer, dermatology and drug delivery markets. The Company's product portfolio is based primarily on intellectual property covering the family of human enzymes known as hyaluronidases and additional enzymes that affect the extracellular matrix. Halozyme's EnhanzeTM technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. The Company has key partnerships with Roche, Baxter, ViroPharma and Intrexon to apply EnhanzeTM technology to therapeutic biologics including Herceptin®, MabThera®, immunoglobulin, Cinryze® and recombinant human alpha 1-antitrypsin. Halozyme's Ultrafast Insulin program combines its rHuPH20 enzyme with mealtime insulins, which may produce more rapid absorption, faster action, and improved glycemic control. The product candidates in Halozyme's pipeline target multiple areas of significant unmet medical need. For more information visit www.halozyme.com.