Halozyme Therapeutics develops a recombinant enzyme that breaks down the hyaluronan in the subcutaneous space. This can either be used as an adjuvant to improve subcutaneous drug delivery or as a stand alone cancer therapy that targets the tumor microenvironment.
Enhanze Injection (PegPH20)-Hyaluronan is a polysaccharide found in the subcutaneous space of the extracellular matrix. Upon hydration, hyaluronan becomes a gel like substance that fills the extracellular space and resists bulk fluid flow, significantly limiting subcutaneous injection volume and speed. In cancers, the density of hyaluronan puts pressure on tumor blood vessels. This creates a hypoxic environment that makes effective drug delivery challenging and also promotes further tumor angiogenesis. The Enhanze injection contains a recombinant version of one of the human hyaluronidases that has been modified to increase circulation half life. This enzyme cleaves the glycosidic linkage between hyaluronan disaccharide, releasing the bound water in the process. This opens up the subcutaneous space and the blood vessels around the tumor, allowing for more rapid administration of cancer therapies. Since hyaluronan promotes angiogenesis, has immunosuppression effects, and also recruits pro-tumor factors, PegPH20 is also being evaluated as a stand alone therapy for different types of cancers.
Breaking the Castle Walls: Hyaluronan Depletion as a Therapeutic Approach to Cancer Therapy
Shepard, HM. Frontiers in Oncology. 2015; 5:192
Intravenous Therapy: A Review of Complications and Economic Considerations of Peripheral Access
Dychter, S; Gold, D; Carson, D; Haller, M. Journal of Infusion Nursing. 2012 Mar. 35(2):84-91.
Recombinant Human Hyaluronidase (rHuPH20): An Enabling Platform For Subcutaneous Drug and Fluid Administration
Frost, GI. Expert Opinions in Drug Delivery. 2007 Jul; 4(4): 427-40.
ENHAZE Drug Delivery Technology: A Novel Approach to Subcutaneous Administration Using Recombinant Human Hyaluronidase 20
Locke, KW; Maneval, DC; LaBarre, MJ. Drug Delivery. 2018 Dec; 26(1)98-106
Original Science Research:
Halozyme, Inc. is listed as an assignee on 47 patents related to hyaluronidases in adjuvants.
The Enhanze Drug Delivery System is currently available in the clinic and is in various stages of clinical trials in combinations with the following therapeutics:
Phase III Trials: Abraxane
Preclinical: PegPHP20 stand alone cancer therapeutic
In addition to the list of disclosed trials, undisclosed therapeutics are currently in pre-clinical development in partnership with Roche, Pfizer, Janssen, AbbVie, Lilly, BMS, Alexion.
- Subcutaneous drug delivery
- Biologic drug formulation
Drug formulation: Halozyme collaborates with pharmaceutical and biotechnology companies to re-formulate existing drugs with the Enhaze system
Drug Development: Halozyme is seeking clinical and non-clinical collaborators to develop PEGPH20 as a stand alone cancer therapy.