Week of April 27 - May 3, 2008

New studies in New York and Tennessee suggest FDA-Approved Gammagard fights Alzheimer's. It appears to target the primary pathway in Alzheimer's.

Gammagard is approved by the FDA as safe for treating certain immunodefficiency disorders. This implies that the main question is how Gammagard helps fight Alzheimer's. Many of the basic safety and side-effect issues that can derail or delay a new drug have already been approved by the FDA. In the USA it is available by prescription as Gammagard-S/D and Gammagard-Liquid, and marketed as KIOVIG in the European Union.

Promising Results & New Insights

“This was the first placebo-controlled clinical trial of Gammagard for Alzheimer’s disease and the results are clearly promising,” commented Dr. Norman Relkin, the New York trial's lead researcher. Dr. Relkin is director of the Memory Disorders Program and behavioral neurologist and neuroscientist at New York-Presbyterian/Weill Cornell Medical Center, and associate professor of clinical neurology at Weill Cornell Medical College in New York City.

The Tennessee study showed that Gammagard contains naturally occurring antibodies that directly bind to different forms of beta-amyloid protein, including oligomers and fibrils. “Observations from this study provide insight into how Gammagard-Liquid may be of potential clinical benefit for Alzheimer’s patients,” said Dave Morgan, director of Neuroscience Research, University of South Florida. “This study suggests that Gammagard-Liquid may target the primary pathway involved in Alzheimer’s disease and justifies additional studies to evaluate whether Gammagard-Liquid can effectively reverse the effects of Alzheimer’s disease.”

Results Published

New York-Presbyterian Hospital/Weill Cornell Medical Center and Baxter International Inc. announced results of a six-month, placebo-controlled Phase II study of 24 patients treated with Gammagard for the treatment of mild-to-moderate Alzheimer’s disease at the American Academy of Neurology (AAN) annual meeting in Chicago. Key findings throughout six months included: measurements of clinical outcome, as well as behavioral outcome and cognitive performance in Alzheimer’s patients treated with Gammagard-S/D and Gammagard-Liquid compared to placebo. Twelve-to-18 month data will be available later this year.

The results suggest that levels of antibodies against beta-amyloid were observed to have increased in the blood and cerebrospinal fluid of patients treated with Gammagard-S/D and Gammagard-Liquid. Beta-amyloid is a substance thought to contribute to Alzheimer’s disease. Clearing this substance from the central nervous system, therefore is hypothesized to help remove or reduce the building blocks of Alzheimer’s.

Baxter supported the study and provided Gammagard-Liquid and Gammagard-S/D for the trial. The precise mechanisms of Gammagard's effects in Alzheimer’s disease are not known. The final results of the study re-affirm the decision of Baxter and the ADCS (Alzheimer's Disease Cooperative Study) to pursue a multi-center, Phase III study evaluating the role of Gammagard-Liquid for the treatment of patients with mild-to-moderate Alzheimer’s disease. The decision was based on results of two completed, open-label clinical studies and the preliminary six-month interim analysis of the Phase II trial. The Phase II study follows an earlier Phase I study in eight patients carried out at New York-Presbyterian/Weill Cornell that was published in the journal Neurobiology of Aging in February 2008.

Phase II Study Design

In the double-blind, placebo-controlled Phase II study, 24 patients in the United States with mild-to-moderate Alzheimer’s disease, who were maintained on standard treatment therapy, were randomly assigned to receive Gammagard-Liquid (eight patients), Gammagard-S/D (eight patients) or saline placebo (eight patients) for six months.

Phase II Results

In August 2007, Baxter and New York-Presbyterian/Weill Cornell announced preliminary Phase II results based on six-month data, indicating the study provided encouragement to carry out a Phase III trial. The criteria for going forward with a Phase III trial were favorable outcomes in Gammagard-S/D and GAMMAGARD LIQUID-treated patients relative to those given placebo. After six months, the group of patients treated with Gammagard-S/D and Gammagard-Liquid averaged 1.52 points higher than placebo-treated patients (+0.27 versus -1.25) on the ADCS-CGIC score, a commonly used measure of outcome in Alzheimer’s disease clinical trials. The ADCS-CGIC is used in Alzheimer’s trials to assess clinically relevant overall changes in Alzheimer’s disease patients determined by patient and caregiver interviews. Patients treated with Gammagard-S/D and Gammagard-Liquid had fewer behavior-related adverse events during the six-month trial and had a more favorable behavioral outcome as measured by the Neuropsychiatric Inventory, a scale used to measure behavioral problems in Alzheimer’s patients. The average change in ADASCog score – a common cognitive testing measure – at six months of treatment was numerically improved in patients treated with Gammagard-S/D and GAMMAGARD LIQUID than placebo (-0.38 versus +2.61), although this difference did not reach statistical significance in the relatively small number of patients studied. Levels of Beta-Amyloid (Secondary Endpoints)

Dr. Relkin also reported observations that levels of antibodies against betaamyloid increased in the cerebrospinal fluid and blood of patients treated with Gammagard-S/D and Gammagard-Liquid, while the levels of beta-amyloid in the blood increased. The antibody and beta-amyloid levels were assessed using ELISA immunosorbant assay, a method used to detect antibodies, and observations were analyzed using parametric statistical analysis.

Tolerability

The study also met its endpoint in assessing the tolerability of GAMMAGARD S/D and Gammagard-Liquid in Alzheimer’s patients. The only treatment-related adverse events that occurred at a greater frequency with Gammagard-S/D and Gammagard-Liquid treatment as compared to placebo were rash and a transient drop in blood count.

Brain Metabolism

Dr. Lisa Mosconi, assistant professor of psychiatry at New York University Medical Center, worked with the New York-Presbyterian/Weill Cornell group on the analysis of brain imaging data from the study and also presented findings at the AAN meeting. She reported that GAMMAGARD-treated participants had observable changes in brain metabolism. While energy metabolism in the brain was an exploratory endpoint in the study it was preserved or improved in 10 out of 13 patients after six months of Gammagard-S/D and Gammagard-Liquid treatment.

“Brain metabolism usually decreases progressively in patients with Alzheimer’s disease,” said Dr. Mosconi. “The changes on PET scans of these Alzheimer’s patients after six months of Gammagard-S/D and Gammagard-Liquid are encouraging.”

The Phase II study also evaluated brain metabolism in patients treated with Gammagard-S/D and Gammagard-Liquid compared to those who received placebo based on 18F-fluoro-deoxyglucose Positron Emission Tomography (PET) (FDG-PET) scans, which are sometimes used in the diagnosis of Alzheimer’s disease. Across brain regions usually affected by Alzheimer’s disease, in this study the Gammagard-S/D and Gammagard-Liquid groups were observed to show 16 percent higher brain metabolism after treatment compared to placebo.

Phase III Study (Last Phase) in Motion

The Phase III study is sponsored by the National Institutes of Health (NIH) and Baxter. The study protocol was submitted to the U.S. Food and Drug Administration for review, with the intention of initiating patient recruitment later in 2008. The trial will include approximately 35 leading academic centers in the United States that are members of the Alzheimer’s Disease Cooperative Study (ADCS). The involvement of the ADCS and NIH in the conduct of the Phase III trial will ensure the highest level of independent scientific evaluation of the potential role of Gammagard-S/D and Gammagard-Liquid in the treatment of Alzheimer’s.

JOINING A CLINICAL TRIAL:

The upcoming clinical trial of Gammagard will be to test its effectiveness in fighting Alzheimer's. If you are interested in participating, the first step is to add yourself to the Alzheimer's mailing list of one of the main clinical trial sites. You can find these sites by selecting LINKS at the top of any page, and then clicking CLINICAL TRIALS.

MORE INFORMATION:

About Gammagard-Liquid and Gammagard-S/D

Gammagard-Liquid 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.

For full prescribing information, please visit:
http://www.gammagardliquid.com
http://www.immunedisease.com/US/patients/safety.html#gamma

About New York-Presbyterian Hospital/Weill Cornell Medical Center

New York-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital New York-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. For more information, visit:
www.nyp.org and www.med.cornell.edu.

About The University of Tennessee Health Science Center

As the flagship statewide academic health system, the UT Health Science Center is focused on a four-tier mission of education, research, clinical care and public service, all in support of a single goal: to improve the health of Tennesseans. For more information, visit www.utmem.edu.

About Baxter

Baxter International Inc., through its subsidiaries, assists healthcare professionals and their patients with treatment of complex medical conditions, including hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other indications. The company applies its expertise in medical devices, pharmaceuticals and biotechnology to make a meaningful difference in patients’ lives.

This article is based on Baxter press releases which include forward-looking statements concerning Gammagard-S/D and Gammagard-Liquid [Immune Globulin Intravenous (IGIV)] relating to clinical trials as well as potential future uses of the products. 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.

BY:

Peter Berger, Editor, Alzheimer's Weekly

Reviewed for medical accuracy by
Dr. Boaz Ancselovic, MD, Geriatrician, Alzheimer's Weekly

SOURCE:

Baxter International, Inc.

COPYRIGHT:

Copyright © 2008. Alzheimer's Weekly LLC. All rights reserved.