ENHANZE® drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20

Drug Deliv. 2019 Dec;26(1):98-106. doi: 10.1080/10717544.2018.1551442.


ENHANZE® drug delivery technology is based on the proprietary recombinant human hyaluronidase PH20 enzyme (rHuPH20; Halozyme Therapeutics, Inc.) that facilitates the subcutaneous (SC) delivery of co-administered therapeutics. rHuPH20 works by degrading the glycosaminoglycan hyaluronan (HA), which plays a role in resistance to bulk fluid flow in the SC space, limiting large volume SC drug delivery, dispersion, and absorption. Co-administration of rHuPH20 with partner therapies can overcome administration time and volume barriers associated with existing SC therapeutic formulations, and has been shown to reduce the burden on patients and healthcare providers compared with intravenous formulations. rHuPH20 (as HYLENEX® recombinant) is currently FDA-approved for subcutaneous fluid administration for achieving hydration, to increase the dispersion and absorption of other injected drugs, and in subcutaneous urography for improving resorption of radiopaque agents. rHuPH20 is also co-formulated with two anticancer therapies, trastuzumab (i.e. Herceptin® SC) and rituximab (i.e. RITUXAN HYCELA®/RITUXAN® SC/MabThera® SC) and dosed sequentially with human immunoglobin to treat primary immunodeficiency (i.e. HyQvia®/HYQVIA®). This article reviews pharmaceutical properties of rHuPH20, its current applications with approved therapeutics, and the potential for future developments.

Keywords: ENHANZE; Recombinant human hyaluronidase PH20; hyaluronan; rHuPH20; subcutaneous.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / metabolism
  • Antigens, Surface / administration & dosage
  • Antigens, Surface / metabolism
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / metabolism
  • Cell Adhesion Molecules / administration & dosage*
  • Cell Adhesion Molecules / metabolism
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Drug Therapy, Combination
  • Humans
  • Hyaluronoglucosaminidase / administration & dosage*
  • Hyaluronoglucosaminidase / metabolism
  • Immunoglobulins / administration & dosage*
  • Immunoglobulins / metabolism
  • Injections, Subcutaneous
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / metabolism


  • Antibodies, Monoclonal
  • Antigens, Surface
  • Antineoplastic Agents, Immunological
  • Cell Adhesion Molecules
  • Immunoglobulins
  • Recombinant Proteins
  • Hyaluronoglucosaminidase
  • hyaluronidase PH-20

Grants and funding

This review was supported by Halozyme Therapeutics, Inc.