Baxter and the Alzheimer's Disease Cooperative Study Group to Pursue a Phase III Study of Gammagard Liquid in Patients with Alzheimer's DiseaseÂ
Preliminary Phase II Results Encouraging and Support Phase III Study
DEERFIELD, Ill, August 28, 2007 - Baxter International Inc. (NYSE: BAX) . and The Alzheimer’s Disease Cooperative Study (ADCS) group today announced the decision to pursue a multi-center U.S. Phase III study evaluating the role of Gammagard Liquid [Immune Globulin Intravenous (Human)] (IGIV) , an intravenous immunoglobulin preparation, for the treatment of patients with mild to moderate Alzheimer’s disease. GAMMAGARD Liquid contains a broad spectrum of immunoglobulins (antibodies), and is indicated as an immunoglobulin replacement therapy in patients with primary immunodeficiency.
GAMMAGARD Liquid is processed from large pools of human plasma. IGIV has been used for almost three decades to treat primary immunodeficiency. IGIV is not currently approved for the treatment of Alzheimer’s disease, and to date has not been established to be effective in this indication. The rationale for testing IGIV as a possible treatment for Alzheimer’s is based on the presence of natural antibodies that are directed against several forms of beta amyloid. Beta amyloid is a protein found in plaques that accumulate in the brains of patients with Alzheimer’s disease, and is considered to play a key role in the cognitive decline observed in these patients. Treatment with naturally occurring antibodies against beta amyloid contained in IGIV may result in clearance of beta amyloid from the brain and dissolution of plaques.
The decision to pursue the Phase III study is based on the results of two completed open-label clinical studies, and the preliminary analysis of interim data from a double-blind, placebo-controlled phase II study by Dr. Norman Relkin and his colleagues at Weill Cornell Medical College in New York City. In this study, 24 patients with mild to moderate Alzheimer’s disease were randomly assigned to receive GAMMAGARD Liquid, GAMMAGARD S/D or placebo (eight patients were treated with GAMMAGARD Liquid, eight patients were treated with GAMMAGARD S/D and eight patients received placebo) for six months. Cognitive, behavioral and functional measures were collected at baseline, three months and six months of treatment. The primary endpoints of the Phase II trial were cognitive function (as measured by ADAS-Cog score) and global function (as assessed by ADCS-CGIC rating). The pre-specified criterion for going forward with Phase III was a favorable outcome in IGIV-treated patients relative to those given placebo. Final results of the analysis of the Phase II study are expected later this year.
The Phase II study follows Dr. Relkin’s earlier Phase I results in eight patients that were reported at the International Conference on Alzheimer’s Disease in Madrid in July, 2006. Although these findings are promising, both studies were small and results must therefore be confirmed in a larger, sufficiently powered study.
The study protocol will be submitted to the U.S. Food and Drug Administration for review in the coming months with the intention of initiating patient recruitment early in 2008. The ADCS Phase III trial is sponsored jointly by the National Institutes of Health and Baxter. The trial will include approximately 35 leading academic centers in the U.S. that are members of ADCS.
GAMMAGARD LIQUID
[Immune Globulin Intravenous (Human)] 10%
GAMMAGARD LIQUID 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 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, e.g. 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 atheroscleÂrosis, 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. DiscontinuaÂtion 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).
GAMMAGARD S/D
[Immune Globulin Intravenous (Human)]
GAMMAGARD S/D 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.
GAMMAGARD S/D must not be used in patients with selective IgA deficiency (IgA, 0.05 g/L) where the IgA deficiency is the only abnormality of concern.
Important Safety Information
Patients may experience severe hypersensitivity reactions or anaphylaxis in the setting of detectable IgA levels following infusion of GAMMAGARD S/D.
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.
GAMMAGARD S/D does not contain sucrose.
GAMMAGARD S/D is made from human plasma. It may carry a risk of transmitting infectious agents, e.g. viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. DiscontinuaÂtion of IGIV treatment has resulted in remission of AMS within several days without sequelae.
Certain components used in the packaging of GAMMAGARD S/D contain natural rubber latex.
IGIV products can contain blood group antibodies that may cause a positive direct antiglobulin reaction and, rarely, hemolysis.
Thrombotic events have been reported in association with IGIV. Patients at risk may include those with a history of atheroscleÂrosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity, hypercoagulable disorders, and prolonged periods of immobilization.
Various minor reactions, such as mild to moderate hypotension, headache, fatigue, chills, backache, leg cramps, lightheadedness, fever, urticaria, flushing, slight elevation of blood pressure, nausea and vomiting, may occasionally occur.
For full prescribing information for GAMMAGARD LIQUID and GAMMAGARD S/D please go to:
http://www.baxter.com/products/biopharmaceuticals/downloads/gammagard_us_pi.pdf
http://www.baxter.com/products/biopharmaceuticals/downloads/gamliquid_PI.pdf
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.
This release includes forward-looking statements concerning IGIV relating to clinical trials and their timing, as well as potential future uses of the product. 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: continuing review of preliminary trial data and the limited number of patients studied to date; additional regulatory and other steps required prior to the initiation of the larger study described in the release; and other risks identified in the company’s most recent filing on Form 10-Q and other SEC filings, all of which are available on the company’s web site. The company does not undertake to update its forward-looking statements.