Initial analysis from an international clinical trial has indicated that the investigational drugs didn’t slow memory loss, cognitive decline in rare, inherited Alzheimer’s.
The clinical trial evaluating whether two investigational drugs can slow memory loss and cognitive decline in people in the early stages of a rare, inherited form of Alzheimer’s disease has yielded disappointing results, an initial analysis of the data has shown, reports Washington University School of Medicine in St. Louis.
Solanezumab and gantenerumab
The study is a phase 2/3 trial led by Washington University School of Medicine in St. Louis through its Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU). The trial separately evaluated the effects of two drugs – solanezumab, made by Eli Lilly and Co., and gantenerumab, made by Roche and its U.S. affiliate, Genentech – in people with a rare, inherited, early-onset form of Alzheimer’s called dominantly inherited Alzheimer’s disease or autosomal dominant Alzheimer’s disease. Such people experience declines in memory and thinking skills starting in their 50s, 40s or even 30s. The initial analysis indicated that neither drug met the primary outcome of the study, which was a slowing of cognitive decline as measured by multiple tests of thinking and memory.
Both investigational drugs are designed to target and neutralize amyloid beta in the brain through different mechanisms and are being evaluated in other, more common forms of Alzheimer’s. The study followed 194 participants for up to seven years; the average was about five years. All participants come from families that carry a genetic mutation that causes early-onset Alzheimer’s dementia. People who inherit the mutation are all but guaranteed to develop symptoms at about the same age their parents did. While devastating for families, such mutations allow researchers to identify people in the early stages of the disease before their behavior and memory begin to change. Participants were randomly assigned to receive solanezumab, gantenerumab or a placebo. Family members who did not have the Alzheimer’s mutations also were included as a comparison. As part of the innovative trial, doses of the investigational drugs were increased during the study to try to enhance potential beneficial effects. The researchers recruited people who were expected to develop symptoms within 15 years of enrolling in the study or who already had very mild symptoms of memory loss and cognitive decline at the trial’s outset. In most cases, their brains already showed early signs of disease. The goal of the study was to determine whether either investigational drug could slow, stop or prevent memory loss and cognitive decline related to Alzheimer’s.
“We will continue until we are successful”
“Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer’s,” said principal investigator Randall J. Bateman, MD, director of DIAN-TU and the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University. “The trial’s innovative design – developed in collaboration with a consortium of pharmaceutical companies, the National Institutes of Health (NIH), regulatory agencies and academic leaders – will make advances for future Alzheimer’s trials. Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s. We will continue until we are successful.”
A more detailed analysis of the trial’s data will be presented for the first time April 2 at the Advances in Alzheimer’s and Parkinson’s Therapies annual meeting in Vienna, followed by presentations at the Alzheimer’s Association International Conference in Amsterdam in July.