Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials

Objective: To evaluate the effects of bapineuzumab on brain beta-amyloid (A beta) burden using C-11-Pittsburgh compound B (C-11-PiB)-PET. Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE epsilon 4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-A beta monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar A beta over 71 weeks using an C-11-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region. Results: A total of 115 carriers and 39 noncarriers were analyzed. The difference (delta) in mean baseline to 71 week change in C-11-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo delta = -0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo delta = -0.068; p = 0.027; 1.0 mg/kg vs placebo delta = -0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results. Conclusions: The C-11-PiB-PET imaging results demonstrated reduction of fibrillar A beta accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical A beta species were inadequately targeted.