Halozyme Products and Clinical Programs
HYLENEX® is FDA approved and it uses rHuPH20 to locally and transiently degrade HA in the subcutaneous space. HYLENEX recombinant is approved to increase the dispersion and absorption of other injected drugs, in subcutaneous fluid administration for achieving hydration, and in subcutaneous urography for improving resorption of radiopaque agents.
ENHANZE™ is a drug delivery platform for clinical trials based on the transient and local degradation of HA by rHuPH20 in the subcutaneous space. HA is present at high concentration in the subcutaneous space and acts as a physical barrier to bulk fluid flow by binding up to 15 water molecules per disaccharide subunit to form a viscous gel-like fluid. The gel-like HA limits fluid flow and is the predominant factor that has limited traditional subcutaneous injections to 1-2 mL. ENHANZE temporarily degrades the HA around the injection site allowing large volumes (up to 300-600 mL and beyond) to be delivered in a single subcutaneous injection. Larger volume injections may allow some biologics and small-molecule drugs that are administered intravenously to be delivered subcutaneously potentially providing an improved patient experience by decreasing infusion times or reducing the needs for multiple injections. Halozyme currently has ENHANZE Technology partnerships with Roche, Baxalta, Pfizer, Janssen, AbbVie and Lilly. ENHANZE is not approved as a stand-alone platform.
PEGPH20, Halozyme’s investigational product, is a PEGylated version of rHuPH20 that is hypothesized to reduce the high levels of HA (HA-High) that are present in some solid tumors including pancreatic ductal adenocarcinoma, 11 Whatcott et al. Clin Cancer Res. 21:15 (2015) non-small cell lung,22 Pirinen et al. Int J Cancer 95:12 (2001) gastric33 Setala et al. Br J Cancer 79:1133 (1999) and metastatic breast cancers.44 Auvinen et al. Am J Pathol. 156:529 (2000) Overexpression of HA in the tumor microenvironment can lead increased interstitial pressure, blood vessel compression and decreased perfusion that may serve as an important mechanism of treatment resistance.66 DuFort et al. Biophys. J, 110:2106 (2016) PEGylation of the enzyme enables administration via intravenous injection, allowing it to circulate longer in the body where it is thought to help degrade HA in the tumor micro environment. PEGylating rHuPH20 increases the circulating half-life of the enzyme increasing exposure and allowing systemic delivery for oncology indications. Degrading HA in animal models with HA-High tumors led to reduced tumor pressure, increased blood flow and increased tumor growth inhibition activity of some small molecule therapies,77 Thompson et al Mol. Cancer Ther. 9:3052 (2010) immune-oncology antibodies,88 Rosengren et al. (2016). AACR Annual Meeting, Poster #4886 and cell-based therapies.99 Manuel et al. Cancer Immunol Res. 3:1096 (2015) Studies are currently ongoing to determine the efficacy and safety in humans. PEGPH20 has not been approved by the FDA, or any other Health Authority.
After administration of PEGPH20, the enzyme can accumulate in the tumor reducing the amount of HA and resulting in re-expansion of the blood vessels. These effects can create a TME that is less favorable to tumor cells. In addition, PEGPH20-dependent blood vessel expansion may lead to a tumor that is more accessible to attack by chemotherapies, monoclonal antibodies, and cell-mediated therapies (for example CAR-T and engineered T cell therapies).