Patients with mild to moderate Alzheimer disease experienced no reduction in cognitive decline or preservation of functional abilities, according to findings of a phase 3 trial of intravenous immunoglobulin (IVIG, Gammagard). The announcement, by trial sponsor Baxter International, follows similar shutdowns within the past year of studies involving 2 other once-promising experimental Alzheimer therapies, monoclonal antibodies called bapineuzumab and solanezumab.
The phase 3 study failed to confirm promising results reported in a small phase 2 trial of 24 patients that was presented last July at the Alzheimer’s Association International Conference. According to press reports, results of that trial indicated that IVIG had halted Alzheimer disease progression over a 3-year period in 4 patients.
Human antibodies in IVIG, which is made from purified human plasma collected from healthy volunteers, offer immune response modulation and anti-inflammatory properties that help treat rare immune-related and neurological conditions. Some physicians have been using IVIG off label to treat patients with Alzheimer disease, but evidence of efficacy has been mostly anecdotal.
The phase 3 trial, Baxter’s Gammaglobulin Alzheimer’s Partnership Study, was a randomized, double-blind, placebo-controlled trial enrolling 390 patients with mild to moderate disease at 45 centers across the United States and Canada. Participants received IVIG (at either a 400-mg/kg or 200-mg/kg dose) or placebo every 2 weeks for 18 months. The study results did not show a statistically significant difference in the rate of cognitive decline or functional ability for those receiving IVIG at either dose as compared with placebo.
Although the study was not powered to show statistical significance among subgroups, Baxter said that the 400-mg/kg treatment showed a positive change from baseline versus placebo in cognition among patients with moderate disease, as well as among carriers of apolipoprotein E4 genetic markers, which are strongly associated with the risk of developing late-onset Alzheimer disease.
The company said in a statement that based on the study results, it “will reconsider its current approach for its Alzheimer’s program and will determine next steps after full data analyses.” Additional analyses from the study, including imaging, will be made available in July at the Alzheimer’s Association International Conference in Boston.