What We Learned From the Latest Alzheimer’s Drug Failure

Another Alzheimer’s drug has failed in a phase 3 trial, the stage right before drugs go to the Food and Drug Administration for approval. Drug comany Eli Lilly developed the medication, called solanezumab, and Columbia University Irving Medical Center led the study.

The failure was officially announced in November 2016, but the study was published in the New England Journal of Medicine yesterday.

Solenezumab was given to people with milder forms of Alzheimer’s and smaller deposits of beta-amyloid, the toxic protein that most scientists believe is behind Alzheimer’s. In an Alzheimer’s brain, beta-amyloid accumulates and forms plaques for reasons that are still unclear to scientists. Solenezumab was designed to help clear those plaques by sticking to the amyloid molecules before they accumulate.

In two previous trials, results seemed to suggest that people in the beginning stages improved on memory tests after being on the drug for a year. For this study, scientists recruited 2,129 people who had signs of beta-amyloid build up and some memory loss, but still performed better on memory tests than their peers with more advanced dementia. In this Phase 3 trial, though, patients who took the drug did not perform much better than their peers who took a placebo after 18 months, and the amount of amyloid scientists measured was not affected, either.

For some, this calls into question amyloid as the best drug target. But researchers point out that it doesn’t mean amyloid isn’t at the heart of Alzheimer’s disease. It could be that even in these patients with mild Alzheimer’s disease, there is already too much amyloid to clear.

“Although we are disappointed that this particular drug did not prove successful, the field is benefiting from each study,” said lead author Lawrence Honig, MD, PhD, professor of neurology at CUIMC. “There is hope that one of the newer ongoing studies may result in an effective treatment for slowing the course of Alzheimer’s disease.”

In an editorial that accompanied the study, Michael Murphy, a professor at the Sanders-Brown Center on Aging at the University of Kentucky, said that amyloid should be reevaluated as the leading theory.

“Although it might not quite be time to give up on [amyloid] immunotherapy for treating Alzheimer’s disease, it would be foolish to ignore the continued failures of antiamyloid approaches,” wrote Murphy. “We may very well be nearing the end of the amyloid-hypothesis rope, at which point one or two more failures will cause us to loosen our grip and let go.”