Anti–β-Amyloid Treatment May Need to Be Started Early
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Bapineuzumab, a monoclonal antibody targeting β-amyloid (Aβ), showed no clinical benefit in patients with mild to moderate Alzheimer disease dementia in 2 recent phase 3 randomized placebo-controlled trials (Solloway S et al. N Engl J Med. 2014;370:322-333). The drug did, however, target and reduce Aβ accumulation in trial participants relative to placebo, according to a substudy that evaluated Alzheimer disease biomarkers. The finding supports “the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted,” the investigators stated (Liu E et al. Neurology. doi:10.1212/WNL.0000000000001877 [published online July 24, 2015]).
Anita Slomski, MA
One of the original 2 trials evaluated the effect of bapineuzumab in apolipoprotein E (APOE) ɛ4 carriers, and the other trial studied the effect of the drug in noncarriers. Bapineuzumab or placebo was administered by intravenous infusion every 13 weeks for 78 weeks. The substudy used carbon 11-labeled Pittsburgh compound B PET imaging to evaluate changes in brain fibrillar Aβ over 71 weeks in 10% of the trial participants—115 carriers and 39 noncarriers.
A significant reduction in Aβ accumulation was reported in the pooled analyses of carriers and noncarriers (0.5-mg/kg or 1.0-mg/kg bapineuzumab dose), and in APOE-ɛ4 carriers (0.5-mg/kg bapineuzumab dose), but not in the trial of noncarriers. Further analysis suggested that the effect of bapineuzumab in reducing brain Aβ was largely seen in patients with mild disease. These findings raise the possibility that initiating treatment earlier in the disease may have a greater effect on brain Aβ and consequently a clinical benefit, according to the investigators.