Solanezumab, a monoclonal antibody-based treatment for Alzheimer’s disease developed by Eli Lilly that targets amyloid plaques, did not significantly slow cognitive decline, according to a report published in The New England Journal of Medicine.
Researchers have proposed that Alzheimer’s disease is caused by the buildup of a sticky protein called beta-amyloid. According to this “amyloid hypothesis,” the protein forms plaques in the brain that damage and eventually destroy brain cells. Solanezumab was designed to reduce the level of soluble amyloid molecules before they aggregate.
The double-blind, placebo-controlled, multicenter phase 3 trial involved 2,129 patients with mild dementia due to Alzheimer’s disease, defined as a Mini–Mental State Examination (MMSE) score of 20 to 26 (on a scale from 0 to 30, with higher scores indicating better cognition). They had amyloid deposition shown by means of florbetapir positron-emission tomography or Aβ1-42 measurements in cerebrospinal fluid. Patients were randomly assigned to receive 400 mg of intravenous solanezumab or placebo every four weeks for 76 weeks.
The primary outcome was the change from baseline to week 80 in the score on the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14). Scores range from 0 to 90, with higher scores indicating greater cognitive impairment. A total of 1,057 patients received solanezumab and 1,072 received placebo. The mean change from baseline in the ADAS-cog14 score was 6.65 in the solanezumab group and 7.44 in the placebo group, with no significant between-group difference at week 80 (difference, −0.80; 95% confidence interval, −1.73 to 0.14; P = 0.10). The change from baseline in the MMSE score was −3.17 in the solanezumab group and −3.66 in the placebo group.
The authors suggest that while it is not certain that this particular strategy or drug could be effective, it is possible that either not enough drug was administered or that the drug needs to be administered earlier in the disease course.
In other ongoing studies, solanezumab is being evaluated in presymptomatic patients at risk of Alzheimer’s disease. Other Alzheimer’s drugs are also in development and being tested at higher doses.
“Although we are disappointed that this particular drug did not prove successful, the field is benefiting from each study,” says lead author Lawrence Honig, MD, PhD, professor of neurology at CUIMC. “There is hope that one of the newer ongoing studies may result in an effective treatment for slowing the course of Alzheimer’s disease.”
The study was designed and funded by Eli Lilly and Company.