David W. Kang, Gerald Y. Fu, Jennifer M. Anderson, and Monica L. Zepeda
Halozyme Therapeutics, Inc., San Diego, CA 92121 USA email@example.com
Subcutaneous (SC) administration of therapeutic antibodies is an attractive alternative to the IV route. However, SC delivery is limited by the volume that can be administered at a single site, requiring the dose to be divided among multiple sites and/or administered more frequently. Two concentrations of recombinant human hyaluronidase (rHuPH20) were assessed in their ability to facilitate a 10 mL SC delivery of immunoglobulin (IgG) using surrogate endpoints for infusion tolerability. Endpoints included tissue pressure, as measured by in-line pressure during and after infusion, and qualitative assessments of the local infusion site. The addition of 20 and 2,000 U/mL of rHuPH20 significantly (p < 0.05) reduced in-line pressures by 45% and 55%, respectively, compared to the control. rHuPH20 also significantly reduced post-infusion pressures while reducing local tissue swelling at the infusion site, suggesting more rapid dispersion of IgG from the local tissue. Additionally, rHuPH20 contributed to the maintenance of skin pliability at the local infusion site. The reduction in tissue pressure, rapid dispersion, and preservation of the skin at the local infusion site suggest potential benefits of rHuPH20 in improving tolerability of SC delivery of large volumes of viscous therapeutics.