On October 4, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported the publication of nonclinical data for PEGPH20 in Clinical Cancer Research, an American Association for Cancer Research (AACR) (Free AACR Whitepaper) journal (Press release, Halozyme, OCT 4, 2018, View Source [SID1234529759]). PEGPH20 is the PEGylated version of Halozyme’s proprietary recombinant human hyaluronidase enzyme, rHuPH20, that temporarily degrades hyaluronan (HA). HA is a naturally occurring glycosaminoglycan that can accumulate in the tumor microenvironment (TME) of certain solid tumor types.
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The paper further characterizes the biological and physical changes associated with HA-accumulating (HA-high) tumors in mouse models demonstrating an association with increased collagen content, high tumor interstitial pressure (tIP), vascular collapse, hypoxia, drug resistance and increased metastatic potential. Treatment with PEGPH20 at the human equivalent dose degraded HA in the TME reversing these changes, and also depleted an important proangiogenic growth factor, VEGF-A165, suggesting that treatment with PEGPH20 may diminish the angiogenic potential of the TME.
"The publication of this preclinical work highlights PEGPH20’s encouraging anti-tumor activity profile through the degradation of hyaluronan. In addition, for the first time, it presents evidence that PEGPH20 depletes stores of VEGF-A165, a key proangiogenic growth factor, suggesting that PEGPH20 may diminish the angiogenic potential of the tumor microenvironment," said Dr. Helen Torley, president and chief executive officer. "These data expand our understanding of the PEGPH20 mechanism of action and provide additional support for the potential for meaningful clinical responses in high hyaluronan accumulating tumors."
The accumulation of HA is common in many cancers, particularly in pancreatic cancer where increased HA accumulation predicts a less favorable outcome. A Phase 3 study evaluating the ability of PEGPH20 plus Abraxane (nab-paclitaxel) and gemcitabine to increase Progression Free Survival and Overall Survival versus Abraxane and gemcitabine alone in metastatic pancreatic ductal adenocarcinoma patients, is under way.
Key findings from the Clinical Cancer Research publication included:
Accumulation of HA in tumors correlated with high tIP, vascular collapse, hypoxia, drug resistance and increased metastatic potential
HA accumulation also correlated with increased collagen content and was associated with an increase in α-SMA
Remodeling of the tumor microenvironment is mediated by the enzymatic removal of tumor HA
Treatment with PEGPH20 at the human equivalent dose depleted tumor-associated VEGF-A165 to an undetectable level potentially reducing the angiogenic potential of the TME
The paper, titled "Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression" was published online in Clinical Cancer Research on September 27, 2018.