PHILADELPHIA, March 16 /PRNewswire-FirstCall/ -- Baxter International Inc. 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(TM) 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.
About Primary Immunodeficiency Disorders
Primary immunodeficiency disorders encompass more than 100 diseases caused by an immune system that does not function correctly. According to the Immune Deficiency Foundation, approximately 50,000 persons in the United States have one of the primary immunodeficiency disorders. For many people with primary immunodeficiency, the cause is a lack of antibodies. IGIV therapy can help restore IgG levels to near normal, helping the immune system function properly and prevent infections or fight them when they occur.
About GAMMAGARD LIQUID(TM) 10%
GAMMAGARD LIQUID 10% (known as KIOVIG(TM) in Europe) is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. These include but are not limited to congenital X-linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
Important Safety Information GAMMAGARD LIQUID
GAMMAGARD LIQUID is contraindicated in patients with known anaphylactic or severe hypersensitivity responses to Immune Globulin (Human). Patients with severe selective IgA deficiency (IgA < 0.05 g/L) may develop anti-IgA antibodies that can result in a severe anaphylactic reaction.
Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number.
Glycine, an amino acid, is used as a stabilizer. GAMMAGARD LIQUID does not contain sucrose.
GAMMAGARD LIQUID is made from human plasma. It may carry a risk of transmitting infectious agents, viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Components used in the packaging of this product are latex-free.
Thrombotic events have been reported in association with IGIV. Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity, hypercoagulable disorders, and prolonged periods of immobilization.
IGIV products can contain blood group antibodies that may cause a positive direct antiglobulin reaction and, rarely, hemolysis.
Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.
Various mild and moderate reactions, such as headache, fever, fatigue, chills, flushing, dizziness, urticaria, wheezing or chest tightness, nausea, vomiting, rigors, back pain, chest pain, muscle cramps, and changes in blood pressure may occur with infusions of Immune Globulin Intravenous (Human).
For full prescribing information, please visit http://www.gammagardliquid.com/.
About Baxter International Inc.
Baxter International Inc., through its subsidiaries, assists healthcare professionals and their patients with the treatment of complex medical conditions, including hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other conditions. The company applies its expertise in medical devices, pharmaceuticals and biotechnology to make a meaningful difference in patients' lives.
About Halozyme Therapeutics, Inc.
Halozyme is a biopharmaceutical company developing and commercializing products based on the extracellular matrix for the drug delivery, oncology, and dermatology markets. The company's portfolio of products is based on intellectual property covering the family of human enzymes known as hyaluronidases. The company's Enhanze Technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. In addition, the company received FDA approval for two products: Cumulase(R) and HYLENEX, for use as an adjuvant to increase the absorption and dispersion of other injected drugs and fluids. The company also has a number of different enzymes in its portfolio that are targeting significant areas of unmet need.
This release includes forward-looking statements concerning the company's plans to initiate Phase III trials of the subcutaneous administration of GAMMAGARD LIQUID alone and with Enhanze Technology and expectations regarding the availability of the results related thereto. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: timely submission and approval of anticipated regulatory filings; the ability of the company to enroll a sufficient number of qualified participants in the proposed Phase III trials; the ability of the company to otherwise successfully initiate the Phase III trials; the ability of the company to complete the Phase III trials or any of them on a timely basis; and other risks discussed in the company's filings with the Securities and Exchange Commission (SEC) that could cause actual results to differ materially from those in the forward-looking statements. The company's SEC filings are available on its website. The company does not undertake any obligation to update any forward-looking statements as a result of new information, future events, changes assumptions or otherwise, and all forward- looking statements speak only as of the time when made. Actual results or experience could differ materially from the expectations contained in the forward-looking statements.
GAMMAGARD LIQUID and KIOVIG are trademarks of Baxter Healthcare Corporation.
Enhanze is a trademark of Halozyme Therapeutics, Inc.
