Halozyme Therapeutics, Inc., a biopharmaceutical company developing and commercializing recombinant human enzymes, has initiated and dosed the first three patients in a clinical trial of Enhanze Technology, Halozyme's enzyme-based drug delivery platform based on recombinant human PH20 hyaluronidase (rHuPH20), intended in this trial to enhance the absorption of a representative large molecule protein therapeutic.
"The initiation of this clinical trial takes us another step closer to further developing the full potential of the human recombinant form of hyaluronidase," stated Richard C. Yocum, MD, Vice President of Clinical Development and Medical Affairs at Halozyme. "If rHuPH20 can be shown to enhance the absorption of large molecule therapeutics and confer benefit either by improved bioavailability, time to absorption, or reduced side effects, this method of drug administration may open up new strategies to treating patients with regard to doses administered, dosing intervals, patient tolerability, patient convenience, and health economics."
As a spreading agent, hyaluronidase has traditionally been used to accelerate the delivery of drugs and fluids, including local anesthetics, other co-injected drugs, and contrast agents, and for subcutaneous (SC) fluid replacement. Although a large body of clinical experience supports the benefits and safety of using hyaluronidase as an adjuvant to increase the absorption and dispersion of co-injected small molecule drugs, clinical studies are needed to support the benefits and safety of recombinant human hyaluronidase use with large molecule agents, such as monoclonal antibodies and other large molecule biologics.
Concerns about the allergenicity and immunogenicity of repeat dosing of older, animal-derived hyaluronidase have limited the use of those products in many clinical settings. The recent availability of rHuPH20, along with its high purity and absence of both animal pathogens and risk of transmissible spongiform encephalopathies, has opened up the possibility of many more potential therapeutic uses of this enzyme.
This current clinical trial is designed to compare the pharmacokinetics (PK), safety and tolerability of a large molecule protein therapeutic agent subcutaneously injected both with and without rHuPH20. The dose escalation, within-patient controlled study will use escalating doses of rHuPH20 and substitute a standard SC injection of the therapeutic agent with a SC injection of the protein therapeutic agent combined with rHuPH20. The study will compare the bioavailability and other PK parameters, along with safety and tolerability, of the two SC injections, one with and one without rHuPH20.