Halozyme begins clinical trial using rHuPH20 for faster insulin product

Halozyme Therapeutics, Inc has started a phase 1 clinical study its proprietary ultrafast rHuPH20 (PH20) hyaluronidase enzyme across three approved prandial (mealtime) insulin analogs.

Halozyme’s randomized, three-way cross-over design, euglycemic clamp study will compare the postprandial pharmacokinetics and glucodynamics of the insulin analogs administered with its proprietary rHuPH20 (PH20) hyaluronidase enzyme compared to each of the analogs alone.

Previous studies conducted by Halozyme have demonstrated that the combination of insulin lispro (Humalog) with PH20 yielded faster systemic insulin absorption, increased peak insulin concentrations, and improved glycemic control that better mimicked the normal metabolic response to physiologic insulin release when compared to insulin lispro alone.

“This clinical study is designed to investigate and compare the pharmacokinetic and glucodynamic effects of our PH20 enzyme administered with each of the three commercially available insulin analogs,” stated Doug Muchmore, M.D., Halozyme’s vice president of clinical development for endocrinology.

Halozyme’s study is expected to provide more insight into how rHuPH20 (PH20) hyaluronidase enzyme may influence these insulin analogues’ effects.

Halozyme’s recombinant human hyaluronidase enzyme, rHuPH20, which temporarily degrades hyaluronan, a structural protein in the interstitial space. This temporary alteration provides an opportunistic window that allows the delivery of injectable biologics such as monoclonal antibodies, as well as small molecules and fluids.

With ecombinant human hyaluronidase enzyme, rHuPH20, many pharmaceuticals that would normally be injected intravenously (IV) can be administered subcutaneously. This change in route of delivery may improve patient convenience, enhance pharmacokinetics, boost efficacy, extend the product lifecycle, and reduce cost, in addition to other attributes.

Halozyme is developing two different products in parallel: recombinant human insulin formulated with PH20 (Insulin-PH20), and a rapid acting insulin analog formulated with PH20 (Analog-PH20).

Halozyme tries to improve glycemic control, lessen hypoglycemia, and lessen weight gain, through a more rapidly absorbed, faster acting insulin product.

A number of Phase 1 and Phase 2 clinical pharmacology trials investigating the various attributes of Halozyme’s insulin product candidates are currently underway.

In a phase 2 clinical trial completed in March 2009, Halozyme compared regular human insulin (Humulin R) with and without PH20 and lispro with and without PH20. The study demonstrated faster insulin absorption and increased peak insulin plasma concentrations in type 1 diabetes patients for the combination of lispro with PH20. The results also showed a significant reduction in postprandial blood glucose levels following administration of a standardized test meal for the analog combination treatment.

In another phase 2 three-way crossover design study began in July 2009 Halozyme compares insulin lispro with PH20 and regular insulin with PH20 to lispro alone. Results from this study in type 2 patients are expected in mid-2010.

In a phase 1 trial started in 1Q09 and is testing regular insulin with PH20, lispro with PH20 and lispro alone.

Halozyme is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the endocrinology, oncology, dermatology and drug delivery markets. Halozyme’s Enhanze technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics.

Halozyme has key partnerships with Roche to apply Enhanze technology to Roche’s biological therapeutics for up to 13 targets and with Baxter BioScience to apply Enhanze technology to Baxter’s biological therapeutic compound, GAMMAGARD Liquid.