DEERFIELD, Ill., July 16, 2013 - Baxter International Inc. (NYSE:BAX) today presented additional data from the Phase III Gammaglobulin Alzheimer's Partnership (GAP) study, including select analyses of subgroups, biomarker and imaging data during the Alzheimer's Association International Conference (AAIC) in Boston, Mass. The GAP study was conducted by Baxter and the Alzheimer's Disease Cooperative Study (ADCS), a clinical trial consortium supported by the United States National Institute on Aging at the National Institutes of Health.
As previously disclosed, the GAP study did not meet its co-primary endpoints of reducing cognitive decline and preserving functional abilities in patients with mild to moderate Alzheimer's disease. While the study was not powered to demonstrate statistical significance among sub-groups within the study population, additional post-hoc and exploratory analyses of the data are ongoing.
Findings of the Additional Analyses To Date
On cognitive measures, an analysis of ApoE4 carrier patients who were treated with the 400mg/kg biweekly IG dose (n=87) found a statistically significant difference (p=0.012) in change from baseline in the 3MS score at 18 months versus placebo. Supplemental neuropsychological tests, including Trails B (a test of executive function, including visual attention and task switching), digit span backward and digit span forward (recall of a series of numbers in the order provided or in reverse order), each showed a numerical difference (p=0.073 and 0.082) in ApoE4 carriers.
Additional results from the analyses found:
- A dose-dependent increase in levels of total IgG in the cerebrospinal fluid (CSF) from baseline (79% increase in the 400mg/kg dosing arm, 37% in the 200 mg/kg arm and 0% in placebo), suggesting Baxter's IG passes through the blood brain barrier.
- A dose-dependent increase in levels of antibodies related to amyloid present in Baxter's IG as measured in the CSF (anti-oligomer and antifibril antibodies).
- A dose-dependent reduction in plasma levels of amyloid beta (Aβ1-42) in Baxter IG treated patients relative to placebo (approximately 17% reduction in the 400 mg/kg arm, 6% in the 200 mg/kg arm, and -3% in placebo).
- A reduction in brain fibrillar amyloid (as measured by PET scan using florbetapir [AV-45]) of 4.1% in patients who received IG at the 400mg/kg every 2 week dose (2.7% and 0.9% reductions in the 200mg/kg and placebo arms, respectively).
- No effect observed in tau and phosphorylated tau levels in spinal fluid.
No new safety signals were identified associated with treatment in this patient population, ages 50-89. The most common adverse reactions (observed in at least 5 percent of patients) during treatment with IG were rash and decreases in hemoglobin. There were no differences in the rate of thromboembolic events in the treated groups versus placebo groups. There were 17 serious adverse reactions considered to be treatment-related in the study (12 in the IG cohorts and five in the placebo cohort).
"The signals identified in the clinical and biological markers in select subgroups in this analysis are intriguing and help contribute to a better understanding of this disease," said Norman Relkin, MD, PhD, from Weill Cornell Medical College and GAP Study leader.
Pre-planned and exploratory analyses on the GAP study findings are ongoing, including reviews of subgroups and compilation of volumetric MRI imaging data, and will be presented at a major medical meeting in the fall.
"We are currently collaborating with scientific experts in the field of Alzheimer's research to further explore these findings," said Ludwig Hantson, Ph.D., President of Baxter's BioScience business.
About the GAP Study
The GAP study was the largest placebo-controlled study of immunoglobulin, and was designed to assess the safety and effectiveness of Baxter's IG as a potential treatment for signs and symptoms associated with Alzheimer's disease. The clinical trial included 390 patients with mild to moderate Alzheimer's disease across 45 centers in the U.S. and Canada. Patients were randomized to receive Baxter's IG at either 400 mg/kg or 200 mg/kg dosing every two weeks for 18 months, or placebo. All patients were required to maintain their treatment regimen of approved medications for Alzheimer's disease symptom management.
About Alzheimer's Disease
Alzheimer's disease (AD) is the most common type of dementia, a general term for memory loss and other intellectual abilities serious enough to interfere with daily life. The neurodegenerative disease is characterized by progressive cognitive, functional, and behavioral impairment. Alzheimer's is now the sixth leading cause of death in the United States, with more than five million people living with the disease today.
Immunoglobulin (IG) is made from purified human plasma, which is collected from healthy volunteers. The immunoglobulin in plasma contains human antibodies that protect the body against infection, offering important immunomodulatory and anti-inflammatory properties that help treat rare immune-related and neurological conditions. IG treatment is administered on an ongoing basis to help patients maintain adequate levels of antibodies. IG has been investigated as a treatment for Alzheimer's disease and is not approved for use in the treatment of the disease.
IMPORTANT RISK INFORMATION for Immunoglobulin (IG) Products
Immunoglobulin is made from human plasma and may carry a risk of transmitting infectious agents. Immunoglobulin products have demonstrated the ability to induce severe hypersensitivity reactions, thrombotic events, hemolytic anemia and renal dysfunction, acute renal failure, osmotic nephrosis, and death in pre-disposed patients. Immunoglobulin contains blood group antibodies that may act as hemolysins. Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IG. Aseptic meningitis syndrome has also been reported following intravenous administration of IG. Non-cardiogenic pulmonary edema (TRALI) has been reported in patients following treatment with IG products.
About Baxter International Inc.
Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.
This release includes forward-looking statements concerning the company's development program investigating the potential use of Baxter IG for the treatment of mild to moderate Alzheimer's disease, including with respect to ongoing additional analyses of the data from the GAP study. 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: completion of additional analyses of the data from the GAP study; actions of regulatory bodies and other governmental authorities; the development of other clinical evidence with respect to the treatment of Alzheimer's disease; and other risks identified in the company's most recent filing on Form 10-K and other SEC filings, all of which are available on the company's website. The company does not undertake to update its forward-looking statements.