SAN DIEGO, June 27 /PRNewswire-FirstCall/ -- Halozyme Therapeutics, Inc. (Nasdaq: HALO) today announced Phase 2 results demonstrating that the subcutaneous coinjection of rHuPH20 (recombinant human hyaluronidase, PH20) with lispro significantly improves postprandial hyperglycemia, reduces hypoglycemia, and accelerates the absorption of mealtime insulin in patients with type 2 diabetes. Significantly more patients receiving lispro+PH20, 71% versus 48%, achieved the American Diabetes Association (ADA) goal of maintaining glucose below 180 mg/dL compared to lispro treatment alone, an indication of reduced hyperglycemia. Fewer patients required treatment for hypoglycemia and the mean minimum concentration for postprandial glucose was significantly higher for the lispro+PH20 combination compared to lispro alone.
Halozyme presented these results at the American Diabetes Association 70th Scientific Sessions today in Orlando, Fla. The results of this study confirm previously reported pharmacokinetic and glucodynamic findings in healthy volunteers and type 1 diabetes patients.
"The new data from our Ultrafast Insulin development program provide further evidence that the combination of our rHuPH20 enzyme with insulin reduces glucose excursions through enhanced insulin absorption," stated Jonathan Lim, M.D., Halozyme's president and CEO. "Less hyperglycemia and hypoglycemia with a faster acting, best-in-class insulin product could lead to a much better treatment for diabetes." The goal of Halozyme's Ultrafast Insulin program is to develop a mealtime insulin for patients with type 1 or type 2 diabetes that allows patients to better manage their blood glucose levels and safely reach treatment goals without excessive hypoglycemia.
Key Findings from the Poster Presentation Today
This study enrolled 23 patients with type 2 diabetes taking high daily doses of insulin (mean daily dose 105U) and compared the pharmacokinetics (PK) and postprandial glucose (PPG) response to a test meal in a three-way crossover design. Patients received lispro with and without PH20 and regular insulin with PH20. The study met the primary endpoint of glycemic excursion 0-4 hours after the test meal. Secondary endpoints included multiple glycemic and PK parameters and hypoglycemia measures.
For lispro+PH20 compared to lispro alone, tmax was reduced from 74 to 43 minutes and Cmax increased from 3175 to 5512 pM/IU (p<0.0001 for both). The combination treatment also produced greater early and reduced late postprandial insulin exposure. Insulin exposure during the first hour increased from 17% to 32% of total exposure, while exposure beyond 2 hours after the meal was reduced from 55% to 37% of total exposure (p<0.0001 for both). These data support previous findings in type 1 diabetes patients that coadministration of lispro with PH20 leads to a faster-in and faster-out profile compared to subcutaneous lispro by itself.
This faster PK profile resulted in significantly reduced hyperglycemia and hypoglycemia. With regard to hyperglycemia, the total 4 hour excursion of greater than 140 mg/mL was reduced by 44% (p=0.048) based on mean AUC for 0-4 hours >140 mg/dL for lispro+PH20 compared to lispro alone. The minimum mean glucose concentration was higher for the lispro+PH20 combination at 89 mg/dL compared to 76 mg/dL for lispro alone (p=0.016) indicating less risk for hypoglycemia. Fewer patients fell below 70 mg/dL with 6/21 in the combination arm and 12/21 in the lispro alone group (p=0.03). In addition, fewer patients in the lispro+PH20 arm required glucose rescue, 4 patients versus 10. The mean dose of lispro was also reduced by 8% for the combination treatment arm at 0.277 U/kg compared to 0.302 U/kg for lispro alone (p<0.015).
Drug related adverse events were rare, mild, and occurred with similar frequency for each of the three study drugs. The PK and glycemic response results for regular insulin+PH20 were comparable to those observed for lispro alone.
Presentation Times for Halozyme Abstracts at ADA
Halozyme's rHuPH20 in combination with insulin will be the subject of three presentations at the American Diabetes Association 70th Scientific Sessions. These include:
- Poster: "Accelerated Insulin PK and Improved Glycemic Control in T2DM patients by Coinjection of Prandial insulin with Hyaluronidase," presentation by Marcus Hompesch, M.D., on Sunday June 27 from 12:00 p.m. – 2:00 p.m. EDT and at the Presidents Poster Session & Reception on Sunday, June 27 from 6:30 p.m. – 7:45 p.m. EDT
- Oral: "Human Hyaluronidase Coinjection Accelerates Insulin Pharmacokinetics and Glucodynamics of 3 Rapid Insulin Analogs," presentation by Linda Morrow, M.D., on Monday, June 28 at 4:30 p.m. EDT
- Poster: "Identification of a Suitable Animal Model for Comparative Pharmacokinetics of Insulin Co-formulated with Recombinant Human Hyaluronidase," presentation by Daniel E. Vaughn, Ph.D., on Sunday, June 27 from 12:00 p.m. – 2:00 p.m. EDT and during the guided audio poster tour on Monday, June 28 from 12:00 p.m. – 1:00 p.m. EDT
Additional information about these abstracts can be found by visiting http://scientificsessions.diabetes.org
Ongoing and Planned Ultrafast Insulin Clinical Trials
One additional clinical trial investigating Halozyme's Insulin-PH20 is underway and two more trials are planned.
- Type 1 treatment study – This Phase 2 clinical trial compares regular insulin+PH20 to lispro alone in type 1 diabetes patients. After a one month observation period that includes dose optimization, patients will be randomized to regular insulin+PH20 or lispro and treated for three months. At the end of three months, patients will crossover to the other study treatment for another three months. The study will evaluate safety and efficacy. The study is fully enrolled with 48 patients and results should be available for presentation in 4Q2010. Patients self administer their insulin on an out-patient basis. ClinicalTrials.gov Identifier: NCT00883558.
- Type 1 and type 2 analog treatment studies – These Phase 2 clinical trials will compare three times daily dosing for analog insulin with and without rHuPH20 with one study being conducted in type 1 patients and the other in type 2 patients. The design will include a one month observation period that includes dose optimization, after which patients will be randomized to analog insulin alone, or analog insulin+PH20. At the end of three months, patients will crossover to the other study treatment for another three months. The study will evaluate safety and efficacy and patients will self administer their insulin on an out-patient basis. Halozyme expects these studies will begin during 3Q2010.
Halozyme Therapeutics is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the endocrinology, oncology, dermatology and drug delivery markets. The company's product portfolio is based primarily on intellectual property covering the family of human enzymes known as hyaluronidases and additional enzymes that affect the extracellular matrix. Halozyme's Enhanze™ technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. The company has key partnerships with Roche to apply Enhanze technology to Roche's biological therapeutics, including Herceptin® and MabThera®, for up to 13 targets, and with Baxter BioScience to apply Enhanze technology to GAMMAGARD Liquid®. Halozyme's Ultrafast Insulin program combines its rHuPH20 enzyme with mealtime insulins, which may produce more rapid absorption, faster action, and improved glycemic control. The product candidates in Halozyme's pipeline target multiple areas of significant unmet medical need. For more information visit www.halozyme.com.
Safe Harbor Statement
In addition to historical information, the statements set forth above include forward-looking statements (including, without limitation, statements concerning, (i) the benefits of insulin plus rHuPH20 combinations, (ii) conclusions drawn from clinical trials, and (iii) future clinical trials) that involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The forward-looking statements are also identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of several factors, including regulatory approval requirements and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the company's reports on Forms 10-K, 10-Q, and other filings with the Securities and Exchange Commission.
Robert H. Uhl
Senior Director, Investor Relations
SOURCE Halozyme Therapeutics, Inc.