Baxter Presents Latest Clinical Trial Results of GAMMAGARD LIQUID Administered Subcutaneously

Phase I/II data showed that Enhanze Technology™ enabled subcutaneous administration of a monthly dose of GAMMAGARD LIQUID in patients with Primary Immunodeficiency

Baxter International Inc. (NYSE: BAX) today announced the preliminary results of a Phase I/II clinical trial, in which subcutaneous infusion (under the skin) of GAMMAGARD LIQUID [Immune Globulin Intravenous (Human)] (IGIV) with Enhanze™ Technology enabled administration of a full monthly dose via a single site to patients with primary immunodeficiency (PID). The results were presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in Philadelphia, PA.



GAMMAGARD LIQUID is approved for intravenous administration, which due to large infusion volumes of the therapy needing to be delivered, can take several hours once a month at a doctor’s office or hospital. By contrast, subcutaneous administration of IGIV has been limited by the inability of the tissue to absorb large volumes of injected drugs, creating the need to administer the therapy in smaller, weekly doses and through multiple injection sites. Subcutaneous administration of GAMMAGARD LIQUID with Enhanze Technology via a single site could allow patients to administer a sufficient dose of IGIV once monthly at home.



In the Phase I/II trial, 10 of the 11 patients studied received monthly doses of subcutaneously administered GAMMAGARD LIQUID with Enhanze Technology of 25.5 to 61.2 grams (255 to 612 mL) in a single site. All patients in the trial received the therapy at infusion rates between 120 mL/hr to 300 mL/hr, similar to infusion rates for intravenous administration. The average bioavailability of the subcutaneously administered combination of GAMMAGARD LIQUID with Enhanze Technology was 92 percent of the traditional, monthly intravenous administration.



“These early results are the latest demonstration of Baxter’s ongoing commitment to innovation and, in particular, to advancing the science of IGIV therapy,” said
Hartmut J. Ehrlich, MD, vice president of Global Research and Development for Baxter’s BioScience business. “While further studies are required to confirm these results, Baxter plans to initiate a pivotal Phase III trial using GAMMAGARD LIQUID with Enhanze Technology pending discussions with regulatory authorities by the beginning of 2009.”



Phase I/II Trial Design and Results



The Phase I/II clinical trial was the result of an agreement between Baxter and Halozyme Therapeutics, Inc., under which Halozyme’s proprietary Enhanze Technology was applied to the development of a subcutaneous route of administration for GAMMAGARD LIQUID.



Halozyme’s Enhanze Technology is based on recombinant human hyaluronidase (rHuPH20), which facilitates dispersion and absorption of subcutaneously injected solutions. The Phase I/II trial evaluated the safety, tolerability and pharmacokinetics of a monthly subcutaneous administration of GAMMAGARD LIQUID with Enhanze Technology in 11 PID patients in the United States. The patients were infused with varying amounts of rHuPH20 with one-, two-, three- and then four-week doses of GAMMAGARD LIQUID to determine the amount of enzyme required to enable a full monthly dose to be infused in a single site at rates equivalent to those administered in intravenous infusions. The trial also evaluated the effect of rHuPH20 on the bioavailability of GAMMAGARD LIQUID administered subcutaneously compared to intravenously.



One patient withdrew from the study, citing moderate discomfort with the one-week dose, while the 10 patients who completed the study experienced mild local reactions that were not dose-limiting, such as swelling and redness. No drug-related allergic reactions occurred. Administration time and flow rates were limited by pump characteristics and not by patient discomfort.



Phase III Trial for Subcutaneous Administration of GAMMAGARD LIQUID



In addition to the announcement of results for the Phase I/II for GAMMAGARD LIQUID and Enhanze Technology, Baxter also announced the initiation of a pivotal Phase III trial of subcutaneous administration of GAMMAGARD LIQUID alone. The Phase III trial will evaluate the bioavailability of GAMMAGARD LIQUID after administration intravenously, subcutaneously or subcutaneously at an adapted dose, as measured by the area under the curve of IgG concentration vs. time curve per week. Final results of the study are expected to become available in 2009.



About Enhanze Technology



Enhanze Technology is Halozyme’s proprietary drug delivery technology based on rHuPH20, a recombinant form of hyaluronidase, a naturally occurring human enzyme. The rHuPH20 mechanism of action is its ability to temporarily break down hyaluronic acid, the space-filling “gel”-like substance that is a major component of subcutaneous tissues. When combined or co-formulated with certain injectable drugs, Enhanze Technology may facilitate the absorption and dispersion of these drugs by temporarily clearing a path through connective tissue. Molecules as large as 200 nanometers may pass freely through the perforated extracellular matrix, which recovers its normal density in 48 hours, leading to a drug delivery platform that does not permanently alter the architecture of the tissue.