A Quantitative Method for Determining Hyaluronan Content in Plasma by LC/MS/MS and Plasma HA as a PharmacodynamicMarker for PEGylated-Hyaluronidase PH20 (PEGPH20) in a Phase 1b Trial for Pancreatic Ductal Adenocarcinoma


Hyaluronan (HA) is a non-sulfated linear glycosaminoglycan comprised of repeating disaccharide
units of n-acetylglucosamineand glucuronic acid. HA is abundant in the extracellular matrix of
tissues (e.g. skin, those undergoing rapid growth and development) and has been associated with
wound repair and aggressive malignancies. In solid tumors, abundant HA has been implicated in
abnormally high interstitial fluid pressures (IFP), poor vascular perfusion, hypoxia, and is associated
with poorer prognosis. PEGPH20, a systemically administered investigational hyaluronidase,
degrades tumor-associated HA leading to an increase in tumor vascular perfusion, a reduction in
IFP/hypoxia, and more efficient delivery of co-administered anti-cancer agents. Quantitation of
plasma HA may provide a useful tool to characterize tumors that accumulate HA and may also be
used as a pharmacodynamic(PD) marker for PEGPH20.