Halozyme Therapeutics announces results of its insulin variability study

Halozyme Therapeutics, Inc. (Nasdaq:HALO) today announced insulin variability study results that demonstrated reduced intrasubject absorption variability for the combination of lispro, a meal time analog insulin, plus PH20 (hyaluronidase) compared to subcutaneous injection of lispro alone. When compared to lispro alone, the combination of lispro with PH20 reduced the variability for early and late insulin absorption, the time to maximum concentration (Tmax), and the area under the curve (AUC) at 15, 30, 60 and 120 minutes. The variability for maximum concentration (Cmax) was not affected. In addition, study results confirmed previously reported acceleration for both insulin absorption and action by coadministration of PH20. The company presented these study results this evening at the Diabetes Technology Society meeting in San Francisco.

“Reduced variability for the combination of lispro with PH20 across a number of key pharmacokinetic measures, especially during the first two hours after administration, is an exciting clinical result,” said Doug Muchmore, M.D., vice president, endocrinology clinical development. “For diabetes patients this could mean more consistent and predictable insulin effects for meal time insulin injections.”

The study enrolled 22 healthy subjects who received two doses of three different treatments: insulin lispro alone, regular insulin with PH20, and insulin lispro with PH20 in a euglycemic glucose clamp trial design. All subjects underwent six clamp procedures. This study reported intrasubject variability for Tmax for lispro alone of 11 minutes, 11 minutes (ns) for regular human insulin, and four minutes (p<.01) for the combination of lispro with PH20. Variability for AUC during the first 30 minutes after injection was 41% for lispro alone but improved to 24% (p<.01) for regular insulin with PH20 and 14% (p<.001) for lispro with PH20. Overall, data were presented demonstrating that timing and degree of insulin absorption between doses administered to the same subjects on different occasions were more consistent when combined with PH20 than for either insulin administered alone.

Intersubject variability for pharmacokinetic (PK) and glucodynamic (GD) measures in the study showed a favorable trend for the combination lispro with PH20 compared to lispro. The study was not designed to test statistical significance for intersubject variability. Intrasubject variability for GD measures in the study also demonstrated favorable trends for the combination of lispro with PH20 compared to lispro alone, and one endpoint measure, the percent of total glucose administered during the first four hours, reached statistical significance. Coadministration of PH20 with both regular insulin and lispro was well tolerated.

Also this evening at the Diabetes Technology Society, Halozyme presented additional new data from the dose-ranging study first shown at the International Diabetes Federation Congress last month. These additional data again confirmed that PH20 at the optimized dose of 5 μg/100 U of insulin accelerated the absorption and action of insulin. Furthermore, PH20 improved the PK dose proportionality responses to prandial insulins across a range of physiologically relevant doses, including 2 to 20 U for insulin lispro and 6 to 24 U for human insulin.

The primary goal of Halozyme’s ultrafast insulin program is to develop a best-in-class insulin product in comparison to the current standard of care analog products that participate in the growing $3 billion prandial insulin market. Halozyme is developing two different products in parallel to explore a maximum range of value creating opportunities: recombinant human insulin formulated with PH20 (Insulin-PH20), and a rapid acting insulin analog formulated with PH20 (Analog-PH20). With a more rapidly absorbed, faster acting insulin product, Halozyme seeks to demonstrate one or more significant improvements relative to existing treatment, such as improved glycemic control, less hypoglycemia, and less weight gain. A number of Phase 1 and Phase 2 clinical pharmacology trials, and registration trial-enabling treatment studies are ongoing or planned, that will investigate the various attributes of Halozyme’s insulin product candidates. A multidose crossover treatment study in type 1 patients is currently underway that compares regular insulin with PH20 to Humalog^® (insulin lispro), where patients self-administer each test drug for three months. Results are expected in 3Q10.