New Prevention Trials Aim to Stop Alzheimer’s

Researchers have made significant strides in improving clinical trials in Alzheimer's disease. New diagnostic tools and results from large studies are changing how we conduct trials and the patients being treated in them.

We learned that almost a third of patients in previous trials for Alzheimer's drugs didn't have the beta-amyloid plaques common in the disease, and therefore didn't have Alzheimer's. Now, more trials ensure that patients actually have the plaques that drugs are designed to treat using beta-amyloid PET scans, other neuroimaging techniques, and spinal fluid tests.

Results from many failed and discontinued drug trials suggest that treating patients with beta-amyloid drugs after they are already diagnosed with Alzheimer's disease may not be effective. Thanks to the beta-amyloid PET scan, we know that beta-amyloid plaques begin accumulating in the brain years—and perhaps even decades—before symptoms appear. This is enabling clinical trials of prevention drugs in patients who have plaques but have not developed symptoms or been diagnosed with Alzheimer's disease.

Five Alzheimer’s prevention trials, all presented at the recent Clinical Trials in Alzheimer's Disease (CTAD) conference, are now underway.

• The A4 Study is testing whether the beta-amyloid antibody solanezumab can prevent Alzheimer's disease in at-risk elderly people. Cognitively normal people are identified as at-risk using a PET scan to assess if they have high levels of beta-amyloid plaques in their brain. Solanezumab failed in a previous clinical trial in patients with Alzheimer's disease, but the researchers think it may be beneficial if given earlier. The trial already has 1,140 participants enrolled and is scheduled to be complete in 2022.
• The EARLY Trial is testing the BACE 1 (an enzyme involved in the process of beta-amyloid generation) inhibitor JNJ-54861911 to see if it can slow cognitive decline in at-risk elderly people. Cognitively normal people are identified as at-risk by a PET scan or cerebral spinal fluid (CSF) tests that indicate high levels of beta-amyloid. It is using a cognitive assessment tool designed specifically for people who do not yet have Alzheimer's disease. The study should be complete in 2024.
• The Generation 1 and Generation 2 trials are testing whether one of two therapies (the beta-amyloid vaccine CAD106 and the BACE inhibitor CNP520) will prevent Alzheimer's disease in at-risk elderly people. Generation 1 will enroll individuals with two APOE4 genes, and Generation 2 will enroll individuals with at least one ApoE4 gene. The study should be complete in 2024.
• The A3 Study will test whether a BACE1 inhibitor (not yet revealed) will slow cognitive decline in at-risk elderly people. Patients will be identified as at-risk based on intermediate levels of beta-amyloid and a genetic test for APOE4. This study will start enrolling patients in 2018.

These prevention trials are critical to testing the "amyloid hypothesis" of Alzheimer's, which posits that the accumulation of beta-amyloid causes Alzheimer's disease. The hypothesis has come into question as many beta-amyloid-targeted drugs have failed in clinical trials. Adherents of the hypothesis say that we must treat people before symptoms of Alzheimer’s emerge, which these trials are doing.

It will be years before the results of these trials are known. But there are many things that you can do right now to reduce your risk for Alzheimer's disease. Visit our First Steps to Protect Your Cognitive Vitality to see where to start.

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