- Systemic treatment with chemotherapy and pegylated enzyme produces
significantly enhanced survival compared to chemotherapy alone -
- Pegylated enzyme well tolerated -
SAN DIEGO, July 22 /PRNewswire-FirstCall/ -- Halozyme Therapeutics, Inc.
(Nasdaq: HALO), a biopharmaceutical company developing and commercializing
products targeting the extracellular matrix, today announced the presentation
of positive pre-clinical animal efficacy data for its pegylated-rHuPH20 enzyme
(PEGPH20) at the American Association for Cancer Research (AACR) Translational
Cancer Medicine meeting in Monterey, CA. The study showed that treatment of
hormone resistant human prostate cancer in tumor bearing mouse models with
intravenous PEGPH20 in combination with the chemotherapeutic drugs, docetaxel
(Taxotere(R)) or liposomal doxorubicin (Doxil(R)) resulted in a substantial
increase in anti-tumor activity. The docetaxel combination treatment
demonstrated significantly enhanced survival compared to treatment with the
chemotherapeutic agent alone. The effects of PEGPH20 were selective to
prostate tumors producing hyaluronan (HA), consistent with the selective
reduction of tumor interstitial fluid pressure (IFP). Treatment with PEGPH20
was well tolerated in non tumor-bearing mice without significant increases in
neutropenia (depletion of neutrophils, a type of white blood cell) compared to
"These findings clearly demonstrate the activity of our long acting
PEGPH20 enzyme candidate against HA-rich tumors in combination with
chemotherapy," said Gregory Frost, PhD, Halozyme's Vice President and Chief
Scientific Officer. "By targeting tumors that overproduce the HA matrix
component, PEGPH20 may selectively attack tumor interstitial fluid pressure
and combined with chemotherapy, reduce tumor burden for a significant number
Halozyme is continuing its pharmacology, manufacturing and toxicology
studies as part of its PEGPH20 development program in oncology. The company is
making preparations for a pre-IND meeting with the FDA later this year to seek
advice with regard to the design of its first-in-human clinical trial and
plans to initiate studies in cancer patients with PEGPH20 during the first
half of 2009.
Study Details and Background
This study utilized three widely accepted animal cancer models: xenograft
PC3, xenograft Du145luc, and PC3-M-luc bone metastases. For the HA-producing
xenograft PC3 model, animals received an intramuscular inoculation with PC3
prostate carcinoma cells in the hind leg in order to generate tumors with high
IFP. When tumor volume reached 400-500 mm(3), a high tumor burden, animals
were randomized to receive one of four possible treatments: PEGPH20 alone,
chemotherapy alone, chemotherapy plus PEGPH20, or placebo. Two
chemotherapeutic agents, docetaxel and liposomal doxorubicin, were tested in
this model. The non-HA-producing xenograft Du145luc model was utilized in a
similar manner with docetaxel. Finally, an HA-producing PC3-M-luc disseminated
bone metastasis model was used to test PEGPH20 alone and in combination with
Xenograft PC3 results
-- Tumor volume growth suppressed significantly. Tumor volume growth over
time was significantly lower in the PEGPH20 plus docetaxel (p<0.01) and
PEGPH20 plus liposomal doxorubicin (p<0.05) groups compared to chemotherapy
alone. These results clearly indicate a synergistic effect with the addition
of PEGPH20 to the docetaxel regimen. Furthermore, a significant reduction in
tumor volume was observed following administration of PEGPH20 alone.
-- Survival for combination treatment was significantly increased.
Docetaxel plus PEGPH20 increased life span by 225% while docetaxel alone
increased life span by 59% relative to control. Furthermore, the survival
benefit produced by the combination treatment was significantly better than
docetaxel alone (p=0.003).
Xenograft Du145luc results
-- Tumor volume growth unaffected by combination treatment, as expected.
Human Du145luc prostate tumor cells do not produce hyaluronan, and no change
in interstitial fluid pressure was observed following PEGPH20 treatment.
Therefore, treatment with an HA-reducing treatment regimen would not be
expected to provide a therapeutic benefit. Results demonstrated no meaningful
difference in tumor volume between the docetaxel alone and PEGPH20 plus
docetaxel treatment groups. In addition, unlike the HA-producing PC3 tumors,
tumor growth curves in the control and the PEGPH20 groups were virtually
superimposable. These findings support the proposed mechanism of action that
only HA-producing tumors would be most susceptible to PEGPH20.
PC3-M-luc bone metastases results
-- Survival benefit demonstrated. Two different combination dosage
regimens of PEGPH20 plus docetaxel demonstrated improved survival compared to
the control group. For this model, tumor cells are injected directly into the
left ventricle and migrate to bone tissue.
Hyaluronan is a dominant constituent of the extracellular matrix in
subsets of many solid tumor types, including prostate, breast, ovarian,
pancreatic, and gastric, where it may increase the resistance to
chemotherapeutic agents. Previous studies presented by Halozyme (Thompson et
al. Proceedings AACR Annual Meeting, Volume 49, April 2008) demonstrated
significant reductions of HA around the tumor, IFP, and tumor water content
after intravenous administration of PEGPH20. Elevated tumor IFP is believed to
limit the response to cytotoxic treatment regimens in many solid tumors.
Removal of peritumoral HA and the lowering of IFP may potentially lead to
improved responses to chemotherapy and a more rapid reduction of tumor volume
that could potentially improve patient survival.
Pegylation refers to the covalent attachment of polyethylene glycol to a
molecule, usually a drug or therapeutic protein. A pegylated molecule may be
masked from the immune system and have a prolonged circulatory time due to a
reduction in renal clearance. The pegylation of rHuPH20 increases its plasma
half-life to greater than 24 hours compared to less than one minute for the
unpegylated enzyme, therefore resulting in a longer duration of action.
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 the safety and efficacy of PEGPH20 in animal models) 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.
Robert H. Uhl
Senior Director, Investor Relations
Karen Sparks / Joleen Schultz
(858) 455-5500, x275/x215
SOURCE Halozyme Therapeutics, Inc.