The safety of recombinant human hyaluronidase PH20 in nonclinical models: An overview of toxicology, pharmacology, and impact of anti-PH20 antibodies.

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis.

Safety of recombinant human hyaluronidase PH20 for subcutaneous drug delivery.

Introduction: The glycosaminoglycan hyaluronan forms a gel-like substance, which presents a barrier to bulk fluid flow in the subcutaneous (SC) space, limiting SC drug delivery volume and administration rates. Recombinant human hyaluronidase PH20 (rHuPH20) acts locally to temporarily remove this barrier, facilitating rapid SC delivery of large volumes and/or high doses of sequentially or co-administered therapeutics.

Areas Covered: An extensive clinical and post-marketing dataset of safety and immunogenicity of rHuPH20 in its current applications with approved therapeutics demonstrates that rHuPH20 acts locally, without measurable systemic absorption at the SC doses used in the approved products, and is well tolerated in combination with several co-administered therapeutic agents across diverse patient groups.