NEW YORK (GenomeWeb) – The Banner Alzheimer's Institute today announced a partnership with Novartis for a trial of two investigational drugs aimed at people with a particularly high risk of developing Alzheimer's at older ages.
The five-year trial is expected to involve more than 1,300 cognitively healthy individuals between the ages of 60 and 75 who have inherited two copies of the apolipoprotin E (APOE4) gene, putting them at increased risk of developing Alzheimer's. About 2 percent of individuals globally carry two copies of the gene, which has been strongly associated with late-onset Alzheimer's, while about 25 percent of people carry one copy of the gene.
The trial will evaluate the efficacy of two different mechanisms, one an investigational anti-amyloid active immunotherapy, which attacks different forms of the amyloid protein, and the other an investigational beta-secretase 1, or BACE, inhibitor, which prevents the production of different forms of the amyloid protein.
The trial is subject to regulatory approval, but is anticipated to begin in the second half of 2015 and will be conducted at about 60 sites in North America and Europe, including BAI's Phoenix headquarters, BAI said. Participants will receive the immunotherapy, or the BACE inhibitor, or a placebo.
Volunteers who meet the study criteria will be asked to submit genetic material, such as a cheek swab, for APOE4 genotyping in order to prescreen participants. Those who are selected for the trial will receive genetic counseling. Those who aren't chosen but who want more information about their chances of developing Alzheimer's will also receive genetic counseling.
The study is partially funded by a $33.2 million grant commitment from the National Institutes of Health, which was awarded in 2013, as well as philanthropic and in-kind contributions by the Banner Alzheimer's Foundation totaling more than $15 million. The project is part of the Alzheimer's Prevention Initiative, a BAI-led international collaboration to accelerate the evaluation of promising prevention therapies. It is also the second major trial associated with the initiative.
In 2012 Genentech, Banner, and the NIH announced the $100 million Autosomal Dominant Alzheimer's Disease trial in Colombia to study healthy individuals who are genetically predisposed to developing the disease at an early age. That study is evaluating the efficacy of Genentech's investigational monoclonal antibody therapy called crenezumab.
As for the Novartis study, BAI said that research into unimpaired individuals with two copies of the APOE4 gene is crucial on several fronts. Because the study targets only 2 percent of the population at particularly high risk for Alzheimer's at advanced ages, "it enables us to evaluate a treatment's biological and clinical effects in the smallest number of people and in a comparatively shortened time frame."
Additionally, the study complements the ADAD trial in Colombia, and because some participants in the new trial will not yet have any amyloid deposits in their brains at the time they are enrolled in the study, "it will provide a better test of the amyloid hypothesis in the more common form of Alzheimer's that develops at older ages," BAI said. The development of clumps of amyloid protein on the brain has been linked with the disease.
Lastly, the study may provide the scientific evidence necessary to progress new but unproven prevention therapies toward regulatory approval while making it possible for researchers to test such therapies in studies with shorter treatment durations.
"We are taking clinical trials to a critical new stage," Pierre Tariot, study director for BAI, said in a statement. "This approach shifts the research paradigm from trying to reverse disease damage to attacking and preventing its cause, years before symptoms could surface."