Halozyme Therapeutics starts phase 2 trial of insulin with rHuPH20 in type 1 diabetes

Halozyme Therapeutics, Inc. today announced it has started a Phase 2 study of proprietary recombinant human hyaluronidase enzyme (rHuPH20) co-formulations with Humulin R (regular insulin human injection) and with Humalog (insulin lispro) in Type 1 diabetic patients.

This study is designed to compare glycemic control of a standardized liquid meal challenge and insulin pharmacokinetics (PK) after administration of each of four study drugs: Humulin R with and without rHuPH20 and Humalog with and without rHuPH20.

"We are proud to begin this Phase 2 clinical trial in our insulin program and believe this study will provide valuable insight into how the co- administration of our rHuPH20 enzyme with two currently available insulin products could lead to significant patient benefits such as better glycemic control, less hypoglycemia, and more convenient injection timing," declared Jonathan Lim, M.D., President and CEO of Halozyme. "We have achieved our goal of advancing our Phase 2 insulin program into the clinic before the end of the year and I congratulate the Halozyme team for its outstanding performance."

This exploratory, crossover design, single blind, open label, liquid meal Phase 2 study is designed to collect data on at least 20 patients who complete the study. The study allows for insulin dose titration and each patient will receive a minimum of four and up to three additional study drug injections that include Humalog and Humulin R with and without rHuPH20. Study drug will be injected subcutaneously into the abdomen immediately prior to ingestion of a standardized liquid meal.

The primary endpoint, a PK measure, will be the area under the curve for plasma insulin concentration from zero to 60 minutes after injection. Secondary endpoints will include additional PK data, as well as blood glucose concentration at various time points. Safety data such as adverse reactions, hypoglycemia, blood chemistry, and injection site tolerability will be collected, measured and evaluated. Patients may be on study for up to an estimated 14 weeks from screening to completion and the results should be available for presentation at a medical or scientific forum in mid-2009.

Halozyme conducted a Phase 1 euglycemic clamp study in 26 volunteer subjects who received an injection of Humulin R or Humalog with and without rHuPH20. The trial showed that the co-injections were well tolerated and demonstrated faster insulin absorption and shorter time to peak concentration for the insulin plus enzyme combination compared to insulin alone. Metabolic effects such as glucose lowering activity for the combination of insulin plus rHuPH20 were also greater and occurred earlier than for insulin administered alone. In addition, the combination of Humulin plus rHuPH20 demonstrated faster insulin absorption and a shorter time to peak concentration when compared to Humalog alone.

Results (http://www.halozyme.com/images/ADA 2008 Poster legal.pdf) of the Phase 1 study were presented at the American Diabetes Association 68th Scientific Sessions in June 2008 as a late breaking abstract. By making mealtime insulin faster acting, which shifts insulin exposure and glucose lowering activity to earlier times and away from late postprandial times, insulin kinetics and activity for the combination of insulin plus rHuPH20 more closely mimics natural, endogenous prandial insulin release.