An international 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. However, the researchers continue to explore data from the trial's cognitive and clinical outcomes, and await analyses of biomarkers and other information so they can further understand the study's results.
The study (ClinicalTrials.gov Identifier: NCT01760005) 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.
Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer's. 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." Randall J. Bateman, MD, principal investigator, director of DIAN-TU and the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University
Despite the trial's results, the study yielded new insight into the development and progression of Alzheimer's, which can inform future research into the disease, including the more common form that typically strikes after age 65, Bateman said. The brain changes that occur as Alzheimer's progresses are much the same in people with the inherited, early-onset and the late-onset forms of the disease.
"Roche and Genentech are proud to work in partnership with Washington University and Lilly on this important study in a rare, inherited form of Alzheimer's disease," said Rachelle Doody, MD, PhD, global head of neurodegeneration at Roche and Genentech. "Along with the broader Alzheimer's community, we are disappointed that this study did not meet its primary objective yet remain confident that these results will help inform the direction of future research. We are grateful to be part of this close collaboration between industry, academia and patients as we continue to tackle the complex challenge of Alzheimer's disease."
Both the early-onset and late-onset forms of Alzheimer's have "silent" phases that begin up to two decades before symptoms arise. The process starts with the accumulation of plaques of the protein amyloid beta in the brain. Eventually, as the disease progresses and the damage to the brain becomes more extensive, people's memory, thinking and behavior start to deteriorate.
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.
"We are grateful to the courageous participants, their families, and clinical investigators for their dedication and commitment to the study," said Daniel Skovronsky, MD, PhD, Lilly's chief scientific officer and president of Lilly Research Labs. "These results reflect the difficult nature of treating Alzheimer's disease and the great need for continued research. If we have learned one thing after more than 30 years of Alzheimer's research, it is that even negative results propel the science forward."
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. Related Stories
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