Pegvorhyaluronidase alfa: a PEGylated recombinant human hyaluronidase PH20 for the treatment of cancers that accumulate hyaluronan

Abstract Hyaluronan (or hyaluronic acid, HA) is a nonsulfated, negatively charged, single-chain megadalton glycosaminoglycan distributed through the body, especially in soft connective tissue. In many solid tumors, HA accumulates in the extracellular matrix, can impede access of anticancer agents, and is associated with an aggressive tumor phenotype. Recombinant human hyaluronidase PH20 (rHuPH20) enzymatically degrades hyaluronan and has been approved by the US Food and Drug Administration to enhance dispersion and absorption of subcutaneously delivered therapies. A PEGylated version of rHuPH20, pegvorhyaluronidase alfa (PEGPH20), has been developed to enable prolonged systemic exposure to rHuPH20 and to investigate the potential therapeutic effects of hyaluronan degradation. In animal models, intravenous pegvorhyaluronidase alfa enzymatically degrades tumor hyaluronan, reduces tumor interstitial pressure, and improves vascular perfusion, resulting in increased intratumoral access of anticancer agents and increased tumor immune cell density. Consistent with these effects, pegvorhyaluronidase alfa has demonstrated antitumor efficacy when used alone or in combination with other anticancer therapies in nonclinical models. In the Phase II HALO 109-202 trial, pegvorhyaluronidase alfa plus nab-paclitaxel and gemcitabine demonstrated favorable activity in patients with pancreatic cancer. A global, multicenter, Phase III trial (HALO 109-301) of pegvorhyaluronidase alfa in patients with pancreatic cancer is ongoing, with completion expected in 2020.