NIA statement on study results suggesting solanezumab does not reduce cognitive decline in people at risk for developing Alzheimer’s

Topline results from a phase 3 clinical trial supported in part by NIA appears to show that the investigational drug solanezumab does not slow cognitive decline in cognitively healthy people who are at risk for memory loss and problems with thinking due to Alzheimer’s disease. The results also suggest that the drug did not prevent the accumulation of brain beta-amyloid, a hallmark of Alzheimer’s.

As NIA awaits more data on these study results, we want to take this opportunity to express our deep gratitude to those who participated in the trial as well as to the researchers who are fervently searching for effective dementia treatments.

Solanezumab was developed by Eli Lilly and Company. The phase 3 study tested the effectiveness of this drug in preventing or slowing the progression of cognitive problems that may happen in older people who are considered to have asymptomatic Alzheimer’s. Although the trial participants had no cognitive problems at the time of the study, it is thought they are at risk for developing dementia because their brain scans indicate high levels of beta-amyloid, a protein that is often found in the brains of people with Alzheimer’s.

Solanezumab is an antibody made to recognize soluble forms of beta-amyloid. Preclinical studies in mice and phase 1 and 2 clinical trials suggested that intravenous injections of solanezumab may increase clearance of beta-amyloid from the brain. However, previous phase 3 studies suggested the treatment may not work for those who already had memory and thinking problems associated with Alzheimer’s. In one study, solanezumab was no more effective than a placebo at slowing cognitive decline in people who had mild-to-moderate levels of Alzheimer’s disease, as determined by a questionnaire designed to evaluate cognitive impairment. Another study involving people who had mild dementia due to Alzheimer’s disease produced similar results. Therefore, the driving hypothesis of this latest study was that solanezumab would work better for people at risk for dementia but who do not yet have symptoms.

NIA also supported a separate study through the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) that tested the effectiveness of solanezumab to prevent or slow cognitive decline in people who are genetically susceptible to early-onset Alzheimer’s. Dominantly inherited Alzheimer’s is a rare form of the disease that typically occurs in a person’s 30s to mid-60s. The study included both symptomatic and asymptomatic subjects as determined by cognitive testing at the time of entry. The results showed that solanezumab was no more effective than a placebo at slowing cognitive decline.

We look forward to a full report of the data to be presented at a scientific meeting later this year. The impact of these findings may help researchers improve Alzheimer’s disease and related dementias prevention and treatment strategies.

Richard J. Hodes, M.D.
Director
National Institute on Aging
National Institutes of Health

This research was funded in part by NIH grants U19AG010483 and R01AG063689.