Halozyme Therapeutics announces Phase 1 clinical study to assess three insulin analogs

Halozyme Therapeutics, Inc. (Nasdaq:HALO) today announced the commencement of a Phase 1 clinical study that will assess the effects of three approved prandial (mealtime) insulin analogs administered with its proprietary rHuPH20 (PH20) hyaluronidase enzyme compared to each of the analogs alone. This randomized, three-way cross-over design, euglycemic clamp study will compare the postprandial pharmacokinetics (PK) and glucodynamics (GD) of the insulin analogs. 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. “To our knowledge, this is the first study that will compare all three analogs in a head-to-head study of this type. It will broaden our experience with additional analogs and provide insight regarding how our enzyme may influence their effects.” Additional information about this study can be found at clinicaltrials.gov using the identifier NCT00979875. Results of this study should be available by 2Q10.

Update on Halozyme’s Ultrafast Insulin Program

Halozyme’s goal 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. We are 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, we seek 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 investigating the various attributes of Halozyme’s insulin product candidates are currently underway.

• Dose ranging PK study – This Phase 1 clinical trial, which has been completed, began in 4Q08 and investigated the optimal insulin/PH20 ratios. Humalog and Humulin^® R were tested with and without PH20 across a range of doses of insulin and concentrations of both PH20 and insulin in this euglycemic glucose clamp study and various PK parameters were measured in approximately 40 healthy subjects. Results of the study have been and will continue to be used to optimize dosing in future trials. Halozyme will present study results at the International Diabetes Federation Congress to be held on October 18-22, 2009 in Montreal and at the Diabetes Technology Society meeting in San Francisco on November 5-7, 2009. ClinicalTrials.gov identifier: NCT00803972.
• Type 1 standard meal study – This Phase 2 clinical trial began in October 2008 and was completed in March 2009. It compared regular human insulin (Humulin R) with and without PH20 and lispro with and without PH20. Results from the study for the insulin analog, lispro, were presented at the American Diabetes Association meeting in June 2009. 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. This study provided confirmation in type 1 diabetes patients of our previous pharmacokinetic findings with an analog insulin in healthy volunteers. Additional results from this study for Humulin R alone and in combination with PH20 have been accepted for presentation at the European Association for the Study of Diabetes (EASD) meeting in Vienna on October 1, 2009. ClinicalTrials.gov identifier: NCT00705536.
• Type 2 standard meal study – This Phase 2 three-way crossover design study began in July 2009 and is fully enrolled with approximately 20 patients. It compares insulin lispro with PH20 and regular insulin with PH20 to lispro alone. The primary endpoint of this trial is the glycemic excursion over the first 4 hours. Secondary endpoints include the comparison of optimum doses of insulin required for glycemic control, as well as various PK, PD and safety endpoints. Type 2 diabetes patients typically must take higher doses of insulin and the effects of our enzyme may produce more pronounced absorption and concentration effects in this patient population. Results from this study in type 2 patients are expected in mid-2010. ClinicalTrials.gov identifier: NCT00916357.
• Intra-subject variability study – This Phase 1 trial started in 1Q09 and is testing regular insulin with PH20, lispro with PH20 and lispro alone. It is a euglycemic glucose clamp study in 20 healthy subjects that measures PK and GD parameters over eight hours on two separate administrations with the same test dose of each study drug. Intrapatient insulin absorption can be highly variable and this study evaluates and quantifies the ability of PH20 to produce a more consistent PK profile relative to the PK variability produced by the insulin analog alone. Information regarding the consistency of insulin absorption and action has been collected and the results have been accepted for presentation at the Diabetes Technology Society meeting in San Francisco on November 5-7, 2009. ClinicalTrials.gov identifier: NCT00862849.

In addition to the clinical pharmacology studies, the following registration trial-enabling treatment studies are ongoing or planned.

• Insulin-PH20 type 1 treatment study – This Phase 2 clinical trial, which began in May 2009, will compare Insulin-PH20 (non-analog insulin) to lispro alone. After a one month observation period that includes dose optimization, patients were randomized to Insulin-PH20 or lispro and will be treated for three months. At the end of three months, patients crossover to the other study treatment for another three months. The study will evaluate safety and efficacy. Roughly 40 patients have been enrolled and results should be available in 3Q2010. Patients will self-administer their insulin three times daily on an outpatient basis. This study will provide insight into the ability of PH20 to improve regular insulin compared to treatment with analog insulin and will also provide important safety information with regard to chronic dosing for our PH20 enzyme. ClinicalTrials.gov identifier: NCT00883558.
• Analog-PH20 type 1 treatment study – This Phase 2 clinical trial, targeted for initiation in mid-2010, will compare one or more Analog-PH20 candidates to analog alone. The double-blind study will be powered to assess safety over three months when administered three times daily with each meal, and to demonstrate the potential benefit of Analog-PH20 relative to the standard of care for key endpoints that may help drive commercial uptake.