<< Back
Halozyme Therapeutics Announces Phase I Clinical Trial Results Demonstrating that the Combination of Recombinant Human Hyaluronidase (rHuPH20) With Humulin R(R) and with Humalog(R) Yields Faster, More Physiologic Insulin Kinetics and Better Predictability

SAN FRANCISCO, June 9 /PRNewswire-FirstCall/ -- Halozyme Therapeutics, Inc. (Nasdaq: HALO), a biopharmaceutical company developing and commercializing products targeting the extracellular matrix, today announced new Phase I data for the company's diabetes mellitus program at the American Diabetes Association's 68th Scientific Sessions. The data showed that combining the company's proprietary recombinant human hyaluronidase enzyme (rHuPH20) with Humulin R(R) (regular insulin human) or Humalog(R) (insulin lispro) yielded pharmacokinetics and glucodynamics that better mimicked physiologic prandial (mealtime) insulin release and activity than Humulin R or Humalog alone.

Key pharmacokinetic (PK) and glucodynamic (GD) improvements observed in the study include:

-- Significantly faster systemic absorption of each insulin, starting with the first observation time point of three minutes after injection
-- Significantly faster and greater glucose lowering activity early after injection
-- Significantly greater peak insulin levels for the same dose administered
-- Significantly lower variability of key PK and GD variables across subjects
-- rHuPH20 in combination with Humulin demonstrated statistically significant improvement across all parameters when compared to Humalog alone

By making mealtime insulins faster, i.e., shifting insulin exposure and glucose lowering activity to earlier times and away from late postprandial times, combination with rHuPH20 yielded a profile of insulin kinetics and activity more like that of natural, endogenous prandial insulin release.

Diabetes mellitus is an increasingly prevalent, costly condition associated with substantial morbidity and mortality. Attaining and maintaining normal blood sugar levels to minimize the long term clinical risks is a key treatment goal for diabetic patients. The timing of insulin administration with meal ingestion is critical to effective control of blood sugar levels. An ideal insulin would closely mimic normal physiologic mealtime insulin release.

"If these insulin kinetics can be replicated in studies with diabetic patients, the co-formulation of rHuPH20 with recombinant insulin products may close the gap between currently available therapies and endogenous physiologic insulin release," explained Richard C. Yocum, MD, Vice President of Clinical Development and Medical Affairs at Halozyme. "The potential benefits of such a combination include better overall glycemic control and simplified injection timing."

rHuPH20 is the active ingredient in an FDA-approved product for use as an adjuvant to increase the dispersion and absorption of other injected drugs. Halozyme plans to conduct additional clinical trials in its insulin development program, including a study in diabetic patients later in 2008.

Study Detail

The Phase I crossover, euglycemic clamp study was conducted in 26 healthy male volunteers. The study had two stages: the first stage compared the PK and GD of Humalog injected subcutaneously (SC) with and without rHuPH20, and the second stage compared the PK and GD of Humulin R injected SC with and without rHuPH20.

Key Results

Compared to Humalog and Humulin R alone, rHuPH20 had the following effects on PK and GD:

-- The median time to maximal insulin concentration (Tmax) decreased significantly: 54% for Humalog (p = 0.0006) and 64% for Humulin R (p = 0.0002).
-- Insulin concentration increased rapidly and substantially. At 3 minutes, when the first post-injection sample was taken, the increase was 335% for Humalog (p = 0.03) and 2,400% for Humulin R (p < 0.0001).
-- The mean maximal insulin concentration (Cmax) was substantially increased: 90% for Humalog (p = 0.0003) and 142% for Humulin R (p < 0.0001).
-- The increase in systemic insulin exposure, expressed as the mean area under the curve (AUC) was significant over the first 30 minutes, when insulin release drives meal ingestion metabolism: 277% for Humalog (p = 0.0008) and 730% for Humulin R (p < 0.0001).
-- The mean AUC from 4 to 6 hours after injection, when insulin still entering the circulation may lead to post-prandial hypoglycemia, showed a substantial decrease: 41% for Humalog (p < 0.0001) and 48% for Humulin R (p < 0.0001).
-- The glucose infusion rate (GIR) AUC from 0 to 1 hour after injection (corresponding to the time of initial meal digestion) increased meaningfully: 102% for Humalog (p = 0.0001) and 142% for Humulin R (p < 0.0001).
-- GIR AUC from 4 to 6 hours, a time when insulin may lead to post- prandial hypoglycemia, was substantially reduced: 29% for Humalog (p = 0.0020) and 26% for Humulin R (p = 0.0265)
-- The inter-subject variability for both PK and GD parameters, as quantitated by the coefficient of variation (CV) and used as an indication of predictability, improved when rHuPH20 was co- administered. For example for insulin PK:
-- The CV for Tmax was reduced by 54% for Humalog and 12% for Humulin R.
-- The CV for Cmax was reduced by 27% for Humalog and 24% for Humulin R.
-- The co-injection of Humulin R, a regular insulin, with rHuPH20 demonstrated reduced Tmax, and tGIRearly50% as well as increased Cmax relative to the fast-acting analog Humalog alone (without rHuPH20):
-- The insulin Tmax for Humulin R with rHuPH20 was 43% shorter than for Humalog alone (p = 0.02).
-- The insulin Cmax for Humulin R with rHuPH20 was 43% greater than for Humalog alone (p = 0.046).
-- The tGIRearly50% for Humulin R with rHuPH20 was 31% shorter than for Humalog alone (p = 0.0004).
-- All injections were well-tolerated, with no serious or severe adverse events (AEs). No injection with rHuPH20 resulted in any AE assessed as related to rHuPH20.

The study results were presented in full at the American Diabetes Association's 68th Scientific Sessions in San Francisco as a late breaking abstract. The poster from the ADA presentation is available on Halozyme's website (www.halozyme.com)

About Halozyme Therapeutics, Inc.

Halozyme is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the drug delivery, metabolism, oncology and dermatology markets. The company's portfolio of products and product candidates is based on intellectual property covering the family of human enzymes known as hyaluronidases. The company's Enhanze(TM) Technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. Its key partnerships are with Roche to apply Enhanze Technology to Roche's biological therapeutic compounds for up to 13 targets and with Baxter to apply Enhanze Technology to Baxter's biological therapeutic compound, GAMMAGARD LIQUID 10%. In addition, the company has received FDA approval for two products: Cumulase(R), for use in in-vitro fertilization, and HYLENEX, for use as an adjuvant to increase the absorption and dispersion of other injected drugs and fluids. HYLENEX is partnered with Baxter International Inc. The Company also has a number of different enzymes in its portfolio that are targeting significant areas of unmet need.

Safe Harbor Statement

In addition to historical information, the statements set forth above include forward-looking statements (including, without limitation, statements concerning (i) the potential benefits of co-formulating rHuPH20 with insulin and an insulin analog and (ii) plans to conduct additional clinical trials) that involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The forward-looking statements are also identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of several factors, including regulatory approval requirements and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the company's reports on Forms 10-K, 10-Q, and other filings with the Securities and Exchange Commission.

SOURCE Halozyme Therapeutics, Inc.
06/09/2008
CONTACT: Robert H. Uhl, Senior Director, Investor Relations of
Halozyme, +1-858-704-8264, ruhl@halozyme.com; or Karen Sparks, x275,
karen@mentus.com, or Joleen Schultz, x215, jschultz@mentus.com, both of
Mentus, +1-858-455-5500
Web site: http://www.halozyme.com
(HALO)

Could not find file '\\pro.dianum.io\irwebpro\content3\IRXMLDATA\17\175436\Disclaimers.xml'.