NewYork-Presbyterian Hospital/Weill Cornell Medical Center announced today the nine-month interim results of an ongoing Phase II clinical trial of GAMMAGARD Intravenous Immunoglobulin (IGIV) for Alzheimer's disease at the Alzheimer's Association International Conference on Alzheimer's Disease (ICAD) in Chicago.
The nine-month results show significantly better global outcomes, cognitive performance and daily functioning in patients treated with IGIV compared to initially placebo-treated patients.
Just last April, at the American Academy of Neurology (AAN) meeting in Chicago, the six-month outcomes of the double-blind, placebo-controlled Phase II trial were presented. Now, interim data from the extension of that study show persistence of benefits for Alzheimer's patients treated continuously over 9 months. This is the first study to show persistence of benefits for Alzheimer's from IGIV with continuous treatment for 9 months. Previous studies discontinued therapy after 6 months.
The lead researcher for the trial is Dr. Norman Relkin, a behavioral neurologist and neuroscientist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. Dr. Relkin is director of the Memory Disorders Program at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and Associate Professor of Clinical Neurology at Weill Cornell Medical College in New York City.
Working in collaboration with Dr. Relkin is Dr. Diamanto Tsakanikas, the neuropsychologist for the Phase II study. Dr. Tsakanikas is Clinical Assistant Attending Neuropsychologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and an Instructor of Neuropsychology in the Department of Neurology & Neuroscience at Weill Cornell Medical College.
Baxter International Inc. supported the study and provided GAMMAGARD Liquid and GAMMAGARD S/D for the trial. GAMMAGARD contains a broad spectrum of immunoglobulins (antibodies), and is indicated as an immunoglobulin replacement therapy in patients with primary immunodeficiency disorders.
In the double-blind, placebo-controlled Phase II study, 24 patients in the United States with mild to moderate Alzheimer's disease were randomly assigned to receive GAMMAGARD LIQUID (eight patients), GAMMAGARD S/D (eight patients) or saline placebo (eight patients). In the open-label extension of this study, all patients were treated for a total of 18 months. The study included a comparison of four dosing regimens of GAMMAGARD, with doses ranging from 0.2 g/kg every two weeks to 0.8 g/kg every month.
Cognitive, behavioral and functional measures were collected at baseline and every three months thereafter. The primary endpoints of the Phase II trial were cognitive function, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog), and global function, as assessed by the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change rating (CGIC). Safety and tolerability of IGIV treatment in Alzheimer's patients were also assessed relative to placebo. Secondary endpoints included effects on biomarkers related to beta amyloid, a peptide related to Alzheimer's disease.
In today's presentation at ICAD, Dr. Relkin reported that subjects who received uninterrupted IGIV therapy for 9 months demonstrated significantly better cognitive and overall clinical outcomes compared to initially placebo-treated subjects. Dr. Relkin also reported that uninterrupted treatment with IGIV resulted in further improvements in activities of daily living.
Statistically significant differences favoring IGIV treatment were observed on the CGIC at 3, 6 and 9 months. After nine months, the group of patients treated with GAMMAGARD averaged 1.4 points higher than initially placebo-treated patients on the CGIC, a commonly used measure of overall outcome in Alzheimer's clinical trials. At six months, the same group of patients had averaged 1.2 points higher than placebo-treated patients on the CGIC.
On the ADAS-Cog, a test of cognition, change scores numerically favored the IGIV-treatment at 3, 6 and 9 months, with the difference reaching statistical significance at 3 and 9 months. The average change in ADAS-Cog score at nine months of treatment favored treatment with GAMMAGARD by 5.4 ADAS points. The average change in ADAS-Cog score at six months of treatment had favored GAMMAGARD by 2.6 ADAS points. In an analysis by dose arm, subjects receiving 0.4g IGIV/kg/2 weeks improved over baseline on ADAS-Cog scores in 4 of 4 cases at 9 months. None of the subjects given placebo initially showed comparable improvements.