Solanezumab Fails to Meet Targets According to New Alzheimer Disease Study Results

Solanezumab (Eli Lilly and Company, Indianapolis, IN) does not slow the progression of cognitive decline from Alzheimer disease (AD) in individuals with the preclinical stage of AD, according to a press release from Eli Lilly and Company. Solanezumab, a humanized monoclonal IgG1 antibody which targets soluble amyloid beta (Aβ), did not clear plaque in individuals studied and was also ineffective at halting the accumulation of additional amyloid for those receiving the drug. There was no statistically significant difference in Preclinical Alzheimer Cognitive Composite (PACC) scores between the intent-to-treat cohort and the control cohort (mean change with solanezumab -1.69 [95% CI: -2.13 to -1.26]; mean change with placebo -1.4 [95% CI: -1.76 to -1.04]; P=.26). PET scans indicated that amyloid plaque accumulated during the study in both cohorts. The researchers noted that higher amyloid levels in the brain at baseline were associated with a greater risk of progression from preclinical to symptomatic AD (P<.001).

The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) study (NCT02008357) is an international phase 3, double-blind, randomized, placebo-controlled study that began in 2013. Adults aged 65 to 85 years old in the preclinical stage of AD were included from 66 sites in the United States, Australia, Japan, and Canada. Participants (n=1150) were included if they scored between 25 to 30 on the Mini-Mental State Examination (MMSE), scored 0 on the Clinical Dementia Rating (CDR) scale, and had a PET scan that showed brain amyloid pathology. Potential participants were excluded if they took acetylcholinesterase inhibitors or memantine; had a serious medical condition, poor venous access, brain infection or malignant disease in the last 5 years; were suicidal; experienced major depression or bipolar disorder within the last 2 years; or had a history of alcohol or drug abuse within the last 5 years. Participants in the intent-to-treat cohort received solanezumab (400-1600 milligrams) intravenously every 4 weeks for approximately 4.5 years, while the placebo cohort received a placebo IV for the same duration. The primary outcome measure was change from the baseline of the PACC score.