Despite some of the headlines that may speed around the internet today, there is still no cure for Alzheimer’s disease, a degenerative brain disease that causes memory loss and dementia. Pharmaceutical companies have sunk billions of dollars into drugs aimed at preventing or reducing the disease’s hallmark plaques, abnormal brain deposits of a protein fragment called β amyloid, but a long list of failed clinical trials has led many to question that strategy. Now, newly published results from a closely watched clinical trial are being hailed as a big win by some in the Alzheimer’s treatment field. The trial data hint that an anti–β amyloid antibody drug called aducanumab warded off cognitive decline in people diagnosed with early Alzheimer’s. But the trial, an early test of the antibody’s safety, is still too small to prove conclusive, leading many others to caution against false hope.
Nearly all the data from new study, published today in Nature, have been publicly presented before at conferences such as the 2015 Alzheimer’s Association meeting in Washington, D.C. This is the first time the results have been written up in a peer-reviewed journal, however, providing a “coherent, comprehensive, carefully vetted presentation of the data,” says neurologist Stephen Salloway of Brown University, one of the study investigators. “This is first time that a β amyloid–lowering drug is associated with a potential clinical benefit.”
Pharmaceutical companies and academic researchers racing to develop anti–β amyloid drugs fervently hope that a fundamental misunderstanding of Alzheimer’s disease is not at the root of past clinical failures. To troubleshoot potential glitches, they’re trying many β amyloid–targeting strategies, from preventing its buildup and removing existing clumps to giving the drugs earlier in the disease. Aducanumab, an antibody made by the pharmaceutical company Biogen, binds to and clears clumps of β amyloid from the brain like many other antibodies that have been tested. But its origin is unique: It was derived from healthy older people who may have some natural resistance to Alzheimer’s disease, Salloway says.
In the yearlong clinical trial, 165 participants with mild cognitive impairment or dementia from Alzheimer’s took either a 1-, 3-, 6-, or 10-mg/kg dose of aducanumab once a month, or a placebo. After 54 weeks, positron emission tomography brain scans revealed that those who had received the drug had fewer β amyloid deposits; the higher the dose, the greater the reduction in β amyloid. That represents a major breakthrough, says Robert Vassar, a neuroscientist at the Northwestern University Feinberg School of Medicine in Chicago, Illinois. “This is a remarkable therapeutic achievement and a tremendous advance for the field.”
More tantalizing, the new trial also produced some indications of a cognitive benefit. Participants who took the largest 10-mg dose showed less decline on one of two memory tests than those receiving lower doses, or the placebo.
Troublingly, however, 40 patients dropped out of the trial midway—half because of adverse side effects such as small hemorrhages and brain swelling. The side effects were more common at higher doses. That has been a persistent problem for those trying to target β amyloid using immunotherapies—a β amyloid vaccine trial many years ago was halted because it triggered dangerous brain inflammation.
Overall, Alzheimer’s researchers are urging caution about the new drug results—even those who are co-authors on the paper. The study was “grossly underpowered” to determine whether cognition was actually better in people who took aducanumab, or a statistical fluke, notes David Knopman, a neurologist at the Mayo Clinic in Rochester, Minnesota, and another trial investigator. Two much larger, 18-month-long phase III trials are now in progress to determine whether the memory benefits hold up in bigger groups—the point at which many other promising Alzheimer’s drugs have failed.