Halozyme Therapeutics, a biopharmaceutical company, has reported positive preclinical animal efficacy data for PEGPH20 monotherapy.
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The study has demonstrated that repeat intravenous treatment with pegylated-rHuPH20 enzyme (PEGPH20) as a single agent in the PC3 mouse model resulted in approximately 70% (p=0.001) tumor growth inhibition compared to controls.
Various prostate cancer cell lines were screened in vitro for the production of pericellular coats comprised of hyaluronan (HA), the substrate for the PEGPH20 enzyme. Several aggressive prostate cancer cell lines that produce HA-rich coats surrounding the tumor cells collapsed in the presence of PEGPH20, the company said.
Moreover, PEGPH20 significantly suppressed the growth of coat producing human prostate cancer cells within a three-dimensional matrix in a dose dependent fashion, suggesting such cells require HA to rapidly expand into the surrounding microenvironment.
Treatment of human PC3 prostate tumors in athymic mice with intravenous PEGPH20 resulted in a rapid, dose-dependent depletion of HA from the tumor microenvironment. Accumulation of HA in tumors such as PC3, correlates with increased tumor growth, metastases and elevated interstitial fluid pressure.
According to the company, continued enzymatic depletion of HA from PC3 tumors with intravenous PEGPH20 was associated with a 70% tumor growth inhibition and an approximate doubling in time to progression. In contrast, no suppression of tumor volume growth or increase in time to progression was observed with PEGPH20 treatment of an HA negative prostate tumor, Du145.
Halozyme continues to prepare for the commencement of a Phase I single agent clinical trial during the first half of 2009 with intravenously administered PEGPH20 in treatment refractory cancer patients. Additional investigations are also underway to explore combinations of PEGPH20 with other targeted and cytotoxic agents for potential clinical investigation.
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