DEERFIELD, Ill., May 7, 2013 - Baxter International Inc. (NYSE:BAX) today announced that its Phase III clinical study of immunoglobulin (IG) did not meet its co-primary endpoints of reducing cognitive decline and preserving functional abilities in patients with mild to moderate Alzheimer's disease. The Gammaglobulin Alzheimer's Partnership (GAP) study was conducted by Baxter in collaboration with the Alzheimer's Disease Cooperative Study (ADCS), a clinical trial consortium supported by the United States National Institute on Aging in the National Institutes of Health.
Topline analyses from the randomized, double-blind, placebo-controlled,
multi-center trial found that after 18 months of treatment, patients with mild to moderate Alzheimer's disease taking Baxter's IG treatment at either the 400 mg/kg or the 200 mg/kg dose did not demonstrate a statistically significant difference in the rate of cognitive decline as compared to placebo (mean 7.4 in the 400 mg/kg group, 8.9 in the 200 mg/kg group, and 8.4 in the placebo group). Results also did not indicate a statistically significant change in functional ability as compared to placebo (mean -11.4 in the 400 mg/kg group, -12.4 in the 200 mg/kg group, and -11.4 in the placebo group).
While the study was not powered to show statistical significance among the sub-groups, in the pre-specified sub-group analysis, the 400mg/kg treatment arm showed a positive, numerical difference in change from baseline versus placebo in cognition as measured by the Alzheimer's Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) and Modified Mini-Mental State (3MS) Examination among both moderate patients and carriers of the ApoE4 genetic marker. These differences ranged between 16 percent and 29 percent.
[A data table is available at: www.baxter.com/gap/baxter_gap_study_data_table.pdf].
"The study missed its primary endpoints, however we remain interested by the pre-specified sub-group analyses, particularly among patients with moderate disease and those who carry a genetic risk factor for Alzheimer's disease, two patient groups that are in great need of advances in care. A detailed analysis of the results from the GAP study continues, and we look forward to a greater understanding of the full data set," said Ludwig Hantson, Ph.D., president of Baxter's BioScience business. "We are grateful for the participation of the patients and physicians in the study and for the dedicated support of the patients' caregivers."
IG was well tolerated in the study and 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).
Based on these results, Baxter will reconsider its current approach for its Alzheimer's program and will determine next steps after full data analyses. The current Baxter studies of IG in mild to moderate Alzheimer's disease will be discontinued. Additional analyses from the study, including imaging, will be made available later this year as part of a full presentation of the GAP study at the Alzheimer's Association International Conference, July 13-18, 2013 in Boston.
The Alzheimer's Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) was used to assess cognition, including decline in abilities such as memory and language (higher scores indicating greater impairment). The Alzheimer's Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) was used to assess functional abilities using a 23-item score (lower scores indicating greater impairment) in activities such as eating, walking, grooming, and dressing. The 3MS is a widely used test for dementia based on the Mini-Mental State Examination (MMSE), but incorporates four added test items, more graded scoring, and some other modifications that are designed to address a broader range of cognitive functions and cover a wider range of difficulty levels (lower scores indicating greater impairment).
"No approved or investigational medication for Alzheimer's disease has succeeded in a clinical trial of this size and duration. Unfortunately, observations of IG seen in earlier phases of studies of Alzheimer's patients did not translate into a positive outcome in the GAP study," said Norman Relkin, M.D., Ph.D., a neurologist from the Weill Cornell Medical College and GAP Study Leader. "Analysis of the full study results is still ongoing. I am optimistic that the knowledge we gain from this study will advance efforts to develop effective treatments for Alzheimer's disease."
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 treated 390 patients with mild to moderate Alzheimer's disease across 45 centers in the U.S. and Canada. Patients were randomized to treatment with Baxter's IG treatment 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.
The company will host a conference call for investors to discuss the topline results on Tuesday, May 7, at 7:00 am CDT. To access the call, please dial (855) 213-3946 (domestic) or (347) 983-2217 (international) and reference conference number 68885488. Please dial in at least 10 minutes prior to the start of the call.
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 is an investigational 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. Immuneglobulin 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 immunoglobulin (IG) for the treatment of mild to moderate Alzheimer's disease, including expectations with respect to additional results from the GAP study and actions with respect to ongoing and future trials. 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: additional analysis of the clinical results from the initial Phase III trial; 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.