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. The immunogenicity profile demonstrates no adverse effects associated with treatment-emergent rHuPH20 antibody responses. Immunogenicity to monoclonal antibodies co-formulated with rHuPH20 shows no clinical difference between SC and intravenous administration. Safety assessments of patient subsets for special populations, including children, elderly patients, and pregnant women, raise no additional safety concerns. EXPERT OPINION The benefits of SC administration for patients and healthcare systems often outweigh those of intravenous administration, driving future initiation of SC-only drug development programs. Injection devices allowing large-volume SC administration could be facilitated by incorporating co-formulated biologics containing rHuPH20.