PEGylated Recombinant Human Hyaluronidase (PEGPH20): transition from a novel functional excipient to an API to increase the chemotherapeutic effectiveness against hyaluronan-rich cancers.

Abstract

rHuPH20 is a novel new functional excipient that can increase SC drug volume, thus facilitating change over from the invasive IV to the more benign SC route. Its PEGylated analog, PEGPH20, using the same mechanism of action as rHuPH20, has shown; and continues to show; promising results when combined and administered IV with chemotherapeutic agents, in treating tumors characterized by high levels of HA in their ECM. However, its non-mutagenic mechanism of action incorporates a hydrodynamic attribute (of reduced viscosity and increased perfusion in the tumor vicinity) combined with the generation of LMHA oligomers; both of which are amenable toward facilitating the metastasis of the existing tumor. This is no different from current chemotherapeutic or radiation therapy regimens where the drugs/radiation itself is not entirely devoid of mutagenic effects and carcinogenesis. Judiciously used, the PEGylated excipient rHuPH20 has the ability to significantly prolong OS in HA-rich tumors, thus making it yet another excipient-to-drug transition instance in an ever expanding armamentarium of ‘bioactive excipients’.