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 dose (n=87) of immunoglobulin (IG), 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 (Aβ 1-42) 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).