AACR presentations show that PEGPH20 produces anti-cancer activity in models of breast, prostate, and brain metastases that produce hyaluronan
SAN DIEGO--(BUSINESS WIRE)--Apr. 20, 2009--
Halozyme Therapeutics, Inc. (Nasdaq:HALO), a biopharmaceutical company
developing and commercializing products targeting the extracellular
matrix, today announced that treatment with PEGPH20
significantly delayed tumor growth in breast and prostate cancer models.
Moreover, in a brain metastasis model, PEGPH20 combined with
chemotherapy showed increased efficacy and PEGPH20 combined with
radiation prolonged survival. PEGPH20 targets and degrades the
hyaluronan (HA) coating that surrounds certain solid tumor cells.
Halozyme presented its findings at the American Association for Cancer
Research (AACR) meeting in Denver.
“These studies advance our understanding of the pharmacology of PEGPH20
as a novel extracellular matrix-targeted approach for the treatment of
solid tumor malignancies,” stated Gregory Frost, Ph.D., Halozyme’s Chief
Scientific Officer. “We are also encouraged by the findings
demonstrating access to tumor hyaluronan in brain metastases, and the
exploratory studies with chemotherapy and radiation.”
Halozyme has recently initiated a Phase 1 single agent clinical trial
with intravenously administered PEGPH20 in treatment refractory cancer
patients. Additional investigations are anticipated to explore
combinations of PEGPH20 with other targeted and cytotoxic agents for
potential clinical investigation.
Summary of AACR Poster Presentations
Halozyme presented the results from three preclinical studies at the
2009 AACR Annual Meeting in Denver on Sunday, April 19, 2009, 8:00 a.m.
to 12:00 p.m. as part of the poster session titled “Targets in the
Microenvironment.” HA is a glycosaminoglycan that frequently accumulates
in the area outside the cell, also known as the extracellular matrix, of
many solid tumors including prostate, breast, lung, pancreas, stomach
and colon. PEGPH20, an enzyme that degrades HA, has been studied in
several animal models utilizing a variety of tumor types.
Antitumor activity of PEGylated recombinant human hyaluronidase
(PEGPH20) in xenograft and syngeneic rat MatLyLu prostate carcinoma
models. Abstract # 260.
In this study, rat MatLyLu hormone refractory HA producing prostate
cancer cells were implanted in the hind legs of nude mice and in the
prostates of Copenhagen rats. Strongly positive tumor HA expression was
confirmed in the animals. A single bolus dose of PEGPH20 produced a
reduction in tumor interstitial fluid pressure of 46% to 68% at 60
minutes after administration. Tumor growth inhibition for the PEGPH20
treated mice was 34% along with a 1.3 fold delay in time to tumor volume
of 1,500 mm3 (p=0.0008 vs. control) on day 9, the final day
of the study. For the rats treated with PEGPH20, tumor growth inhibition
of 46% (p=0.001) was observed at day 6 with an approximate 1.4 fold
delay in the time for tumors in the treated animals to reach 3,500 mm3.
PEGylated human recombinant hyaluronidase (PEGPH20) removes
peritumoral hyaluronan and increases the efficacy of chemotherapy and
radiotherapy in an experimental brain metastasis model. Abstract #
Hormone refractory human PC3 prostate cancer cells were injected into
the brains of nude mice and disruption of the blood brain barrier was
confirmed on days 11, 15, 22 and 40 of the study. Twice-weekly
intravenous (IV) injections of PEGPH20 on days 12 through 38 resulted in
a sustained degradation of HA from tumor cells in the brain. Mice
bearing PC3 tumors were randomized into one of two groups; chemotherapy
treatment to begin on day 8 or radiation commencing on day 14 of the
study. The chemotherapy group received once weekly IV docetaxel for four
weeks and the radiation group received four whole brain irradiation
treatments every three days. IV PEGPH20 was administered prior to
treatment with chemotherapy or radiation. Docetaxel alone showed minimal
anti-tumor activity in this model but the combination of docetaxel and
PEGPH20 prolonged median survival time by 20% (NS). Radiation plus
PEGPH20 improved survival by 45% relative to control (p=0.0028) and
demonstrated a favorable trend (NS) relative to radiation treatment
alone. The small sample size of six may have limited the power of this
study to achieve significance. Additional brain metastasis studies are
underway with larger sample sizes to better characterize PEGPH20
combination treatment in this model.
PEGPH20: PEGylated recombinant human hyaluronidase antitumor activity
in the 4T1 orthotopic breast carcinoma model. Abstract # 267.
This study investigated the in vitro and in vivo effects of PEGPH20 on
the 4T1-GFP mouse breast carcinoma line. When grown in culture as a
monolayer, 4T1-GFP cells produced large pericellular HA matrices that
were absent when incubated with PEGPH20. 4T1-GFP cells co-cultured with
PEGPH20 resulted in suppression of cell growth, a reduction in
fibroblast/tumor hybrid spheroid diameters and volume, and a
significantly reduced cell fraction survival. Nude mice inoculated with
4T1-GFP cells in mammary fat pads were randomized to receive control
buffer or three different doses of PEGPH20 on days 0, 2, 4, 7, 9, and
11. Treatment with PEGPH20 resulted in dose dependent degradation or
complete removal of tumor HA and statistically significant tumor growth
inhibition of 43% to 61% at day 14 of the study. Time to tumor volume of
1,500 mm3 was 17 days for controls and 29 days for the
PEGPH20 treated animals (p<0.05) resulting in a 1.7 fold advantage for
the treatment group.
Pegylation refers to the covalent attachment of polyethylene glycol to a
molecule, usually a drug or therapeutic protein. The pegylation of the
rHuPH20 enzyme 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 endocrinology,
oncology, dermatology and drug delivery markets. The company's portfolio
of products and product candidates is based on intellectual property
covering the family of human enzymes known as hyaluronidases and
additional enzymes that affect the extracellular matrix. Halozyme’s
Enhanze™ Technology is a novel drug delivery platform designed to
increase the absorption and dispersion of biologics. The company has key
partnerships with Roche to apply Enhanze Technology to Roche’s
biological therapeutics for up to 13 targets and with Baxter BioScience
to apply Enhanze Technology to Baxter’s biological therapeutic compound,
GAMMAGARD LIQUID. Halozyme’s research pipeline candidates target
significant areas of unmet medical need. For more information visit www.halozyme.com.
Safe Harbor Statement
In addition to historical information, the statements set forth above
include forward-looking statements (including, without
limitation, statements concerning the results of studies and benefits
associated with PEGPH20) 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
Source: Halozyme Therapeutics, Inc.
Halozyme Therapeutics, Inc.
Robert H. Uhl
Director, Investor Relations