Phase 1 Study For Halozyme's Insulin-PH20 Published, Highlights Findings For Faster Acting Insulin Formulations

Main Category: Diabetes
Also Included In: Clinical Trials / Drug Trials
Article Date: 02 Jun 2009 - 0:00 PDT

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Halozyme Therapeutics, Inc. (Nasdaq: HALO), announced publication of a Phase 1 study reporting an acceleration of insulin absorption and increased insulin effects within minutes after co-administration of its hyaluronidase (PH20) enzyme with two mealtime insulin products, Humulin® R (regular human insulin) and Humalog® (insulin lispro). A rapid and short-acting insulin profile would more closely mimic the mealtime insulin release that occurs in non-diabetics and could lead to improved treatment for diabetes patients. These results were published in the June 2009 issue of the journal Diabetes Technology & Therapeutics.

"The faster onset and faster offset of glucose effects for insulin plus PH20 observed in this study may lead to a superior treatment for diabetes," stated Douglas B. Muchmore, M.D., vice president, endocrinology clinical development at Halozyme. "That profile may meet the postprandial insulin needs of both type 1 and type 2 diabetics with greater precision and efficacy." The benefits of more rapidly acting insulin may lead to a lower incidence of hypoglycemia, insulin dose reduction, greater convenience to the patient, or less weight gain.

This Phase 1 study investigated the pharmacokinetics (PK) and glucodynamics of Humalog and Humulin R with and without Halozyme's recombinant human hyaluronidase enzyme in 26 healthy male volunteers. After fasting overnight on two separate occasions, 12 subjects received 20 U of insulin lispro with and without PH20 and 14 subjects received 20 U of regular insulin with and without PH20 as subcutaneous injections in the abdomen. A euglycemic clamp procedure was performed and maintained for 6 hours. Administration of hyaluronidase facilitates the dispersion and absorption of co-injected drugs by allowing greater capillary bed exposure.

Key Findings from the Published Study

This clinical trial demonstrated faster systemic insulin absorption, enhanced systemic exposure, and accelerated glucose metabolism for both of the insulin plus PH20 combinations compared to either insulin alone. All injections were well tolerated.

- PH20 reduced the time to maximum glucose infusion rate (tGIRmax) by 41% for Humalog (P = 0.006) and by 35% (P = 0.01) for Humulin R. The addition of PH20 significantly increased early glucose metabolism during the first two hours after injection and significantly reduced late metabolism, 4-6 hours after injection.

- The time to maximum (tmax) insulin concentration with co-administration of PH20 was reduced for Humalog by 51% (P = 0.0006) and for Humulin R by 58% (P = 0.0002). This indicates faster insulin absorption with PH20.

- Co-administration of PH20 increased maximum insulin concentration (Cmax) for Humalog by 90% (P = 0.0003) and for Humulin R by 142% (P < 0.0001).

- The addition of PH20 significantly reduced intersubject variability as measured by the standard deviation for insulin tmax and for the coefficient of variance for Cmax for both of the insulin-PH20 combination treatments.

Additional clinical trials investigating Halozyme's Insulin-PH20 are currently underway and more trials are planned. Interim results of a Phase 2 investigation will be presented at the upcoming American Diabetes Association 69th Scientific Sessions on June 6, 2009 in New Orleans.

Source
Halozyme Therapeutics, Inc.