One more hopeful answer to Alzheimer's disease has flunked out in a Phase III trial that held plenty of promise.
In an 18-month placebo-controlled trial known as GAP (Gammaglobulin Alzheimer's Partnership), patients received intravenous immunoglobulin (IVIG). Against hopes, the treatment failed to halt the progression of the disease.
Specifically, there was no significant difference in the rates of cognitive or functional decline (the primary endpoints of the trial) between IVIG and placebo, according to Baxter International, the trial's sponsor.
Higher dose produced small advantage over placebo
In the GAP trial, 390 patients had been randomized to one of two IVIG doses (200 or 400 mg/kg every two weeks) or placebo. Two scales were used to determine endpoint efficacy: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) for cognitive impairment, and the Alzheimer's Disease Cooperative Study's Activities of Daily Living (ADL) index as the measure of functional ability.
According to Baxter, while there had been a very small advantage over placebo in the group receiving the higher dose of IVIG, it was not considered statistically significant, and no difference at all was found in the ADL index scores.
Baxter to continue research
Baxter will discontinue other ongoing studies of IVIG in mild to moderate Alzheimer's. However, they aren't ready to abandon the treatment completely as there was evidence of some efficacy at the higher dose. In a statement, the company said:
While the study was not powered to show statistical significance among the subgroups ... the 400 mg/kg treatment arm showed a positive, numerical difference in change from baseline versus placebo in cognition as measured by the 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% and 29%. Based on these results, Baxter will reconsider its current approach for its Alzheimer's program and will determine next steps after full data analyses.
Data will be reported in July at the annual Alzheimer's Association International Conference in Data.
These early Phase III data are a let-down compared to the results of the Phase II trial reported on last year, which prompted this Phase III trial. In that 24-patient trial, IVIG had halted progression of the disease over a three-year period.
Source: MedPage Today
