- Product appears safe with no dose-limiting toxicities - - Chemophase dose for pivotal trials successfully determined -
SAN DIEGO, June 30 /PRNewswire-FirstCall/ -- Halozyme Therapeutics, Inc.
(Nasdaq: HALO), a biopharmaceutical company developing and commercializing
products targeting the extracellular matrix, today announced a status update
for its continuing Phase I/IIa Chemophase(R) clinical trial in the treatment
of superficial bladder cancer. Based on the results, the Chemophase
combination treatment of mitomycin plus the recombinant human hyaluronidase
(rHuPH20) enzyme was well tolerated and appears safe. The study reported no
dose-limiting toxicities and no observed side effects attributable to the
enzyme, and established the dose for subsequent clinical trials, therefore
achieving the pre-defined primary objective of the study. In addition, there
were no neutralizing antibodies to rHuPH20 detected and the plasma
concentration of mitomycin was either non-measureable or negligible and well
below the threshold that may be predictive for myelosuppression (a decrease in
bone marrow activity, resulting in fewer red blood cells, white blood cells,
and platelets).
The study also provided support for future pivotal trial development that
will incorporate the highest combination dose studied in the current trial,
mitomycin plus 800,000 Units of rHuPH20. Commenting on the results, Richard
C. Yocum, M.D., Vice President of Clinical Development and Medical Affairs at
Halozyme stated, "We are pleased the study demonstrated that Chemophase was
well-tolerated and produced no dose-limiting toxicities and we look forward to
advancing the agent into pivotal studies."
Given the success of this ongoing Phase I/IIa trial in determining the
dose for subsequent trials and demonstrating the safety and tolerability of
induction and maintenance dosing of Chemophase, Halozyme is making
preparations to request meetings with FDA and European regulators to discuss
the optimal regulatory pathway to drug approval. Based on the outcome of
these discussions, Halozyme plans to initiate its Chemophase pivotal clinical
program in 2009.
Phase I/IIa Chemophase Clinical Trial Details
The study enrolled 27 patients among four investigational sites. Each
patient received fixed doses of 40 mg mitomycin plus doses of rHuPH20
according to assignment to one of five pre-defined dose cohorts. All 15
patients in cohorts one through four have completed induction therapy
consisting of six weekly intravesical (into the bladder) instillations of
Chemophase, with rHuPH20 doses of 20,000, 60,000, 200,000, and 400,000 Units,
respectively. The fifth cohort consisted of 12 patients who received the
highest weekly dose of rHuPH20 at 800,000 Units during the induction phase.
This cohort has now entered the maintenance therapy period of the study with
patients receiving the same Chemophase treatment every three months until the
patient reaches two years on study or has a tumor recurrence. Based on the
date of enrollment of the last patient, dosing may continue through September
2009.
Tumor recurrences require repeat surgical resections, which can lead to
morbidity and may eventually require removal of the entire bladder. Reducing
the frequency of recurrence can minimize these adverse consequences. Even
with the current standard of care, after transurethral resection of non-
muscular invasive bladder cancer followed by currently available intravesical
therapy, patients typically experience a tumor recurrence rate of 40% to 85%,
of which 50% will recur within the first year. The clear need for more
effective treatment creates an opportunity for a therapeutic approach that
improves disease-free survival for these patients.
Although this Phase I/IIa study was designed primarily to assess safety
and optimal dosing of Chemophase, each patient is to be followed on study
until the time of tumor recurrence. The clinical course and risk of
recurrence and progression for this cancer are highly variable and tumor
recurrence data are collected in the study for descriptive-only purposes. As
of this time, each of the 27 patients has been on study for at least 10 months
(or had recurrence prior to 10 months). As of the 10-month follow-up, tumor
recurrence in all 5 cohorts has been reported for 8 of the 27 patients (30%).
The single-arm, non-comparative design of this trial does not facilitate
drawing conclusions on the secondary study objective of anti-tumor activity
based on tumor recurrence rates. Non-muscle-invasive bladder cancer is
markedly heterogeneous due to variability in tumor and histological grading,
risk factors such as tumor size and multiplicity, number of prior recurrences,
and the significant variety of different post-resection therapeutic regimens
employed, which makes comparison of tumor recurrence data across different
clinical trials difficult. Without proper controls and an adequate balance of
risk factors, reliable conclusions may not be drawn from these descriptive-
only data.
About Bladder Cancer
The American Cancer Society has estimated that 67,000 new cases of bladder
cancer would be diagnosed in the U.S. in 2007. Globocan Data estimated that
147,000 new patients would be diagnosed with bladder cancer in Europe in 2007.
According to these sources, there are 500,000 bladder cancer patients in the
U.S. and more than 900,000 in Europe. Published research by Botteman et al.
(PharmacoEconomics 2003) indicates that bladder cancer is the fifth most
expensive cancer to treat. The initial treatment of this cancer is surgical
removal of the tumor. Because of the high frequency of early recurrences of
the tumor, patients are usually prescribed additional therapy to prevent or
delay such recurrences. This additional therapy generally consists of
immunotherapy or chemotherapy drugs instilled directly into the bladder.
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) discussion with the FDA and European regulators regarding the
optimal regulatory pathway to drug approval and (ii) the timing of Phase
II/III clinical trial initiation) 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.
Halozyme ContactMedia Contacts
Robert H. Uhl Karen Sparks / Joleen Schultz
Senior Director, Investor Relations Mentus
(858) 704-8264 (858) 455-5500, x275/x215
ruhl@halozyme.com karen@mentus.com
jschultz@mentus.com
SOURCE Halozyme Therapeutics, Inc.
