The drug makers Biogen and Eisai have decided to abandon late-stage testing of a promising new drug for Alzheimer’s disease, after deciding that it would fail to help patients. The decision left people with Alzheimer’s disease deeply disappointed, and underscores the difficulty of developing new treatments for a disease that affects more than five million Americans and many more worldwide.
The experimental drug, aducanumab, had shown some promise in earlier, smaller clinical trials in reducing declines in memory and thinking skills in people in the early stages of Alzheimer’s disease. That had led the companies to pursue testing in large numbers of people. But a review of data found that the drug was not working to prevent declines in memory and thinking skills.
Aducanumab is what is known as a monoclonal antibody drug. It targets beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer’s disease. Researchers had hoped that preventing the buildup of beta-amyloid, which clumps together to form plaques, also called amyloid plaques, might halt the loss of brain cells.
But the failure of the drug casts doubt on the best approach to finding new ways to treat Alzheimer’s disease. It also brings back to the forefront the notion that the way clinical trials for Alzheimer’s are designed might not be optimal. Perhaps some of the treatments would work but at an earlier stage of the disease (see below). Perhaps they would work for a certain sub-group of the patients but not for all, and if that is the case, how do you best categorize those patients?
Dozens of other experimental Alzheimer’s drugs have shown promise in early testing, only to fail in late-stage testing. In the past two decades, there have been more than 140 unsuccessful attempts developing drugs for Alzheimer’s disease, according to the Pharmaceutical Research and Manufacturers of America, a trade group.
Evidence suggests that brain changes in Alzheimer’s typically begin years prior to the memory loss and other symptoms that lead to a clinical diagnosis. As the disease progresses, declines in memory, behavioral changes and problems with completing day-to-day tasks become more evident.
Many experts think that drugs to combat Alzheimer’s progression may be most effective at the earliest stages, even before symptoms become evident and damage to the brain becomes widespread. More research to understand what causes Alzheimer’s, and how it might be treated, is critical for finding a cure for the disease.
Currently, only four drugs have been approved to treat Alzheimer’s disease itself. They may ease symptoms for a time, but they do nothing to stop the relentless downward progression of disease.
New basic research is needed to understand what causes Alzheimer’s disease, and how it might be treated or prevented or its progression slowed. A number of drug companies are continuing to test dozens of experimental drugs that look at various possible mechanisms for the disease, including inflammation, the immune system, various infections and a brain substance called tau. Other drugs that target beta-amyloid are also undergoing testing.
By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.
Source: Biogen, Inc.