Anti-Amyloid Therapy Fails to Improve Outcomes in Alzheimer Disease

Allan S. Brett, MD

Two monoclonal antibodies had little effect on declines in cognition.

The pathology of Alzheimer disease (AD) includes deposition of β-amyloid peptide; a proposed therapeutic strategy is to administer monoclonal antibodies directed against this peptide. Researchers now report findings from industry-sponsored phase 3 trials of two such antibodies — bapineuzumab and solanezumab — that are directed against two different regions of β-amyloid.

In these trials, about 4500 patients with mild-to-moderate AD (2052 in the solanezumab studies and 2452 in the bapineuzumab studies) were randomized to the active drug or placebo. About half of patients were carriers of the apolipoprotein E e4 allele (a risk factor for late-onset AD). Compared with placebo, neither of the two drugs was associated with statistically significant differences for primary outcomes that included changes in cognition and functional disability scores at 18 months. A beneficial effect of borderline statistical significance was noted in a subgroup of solanezumab-treated patients with mild AD.

Citation(s):

Doody RS et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med 2014 Jan 23; 370:311.

Salloway S et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med 2014 Jan 23; 370:322.