The latest trial of the drug solanezumab, made by Eli Lilly, failed to show much effect in people with the mildest form of Alzheimer’s disease.
The study, published in the New England Journal of Medicine, is the formal report of the results that Lilly announced in November 2016. At the time, the company also decided it would not attempt to market the drug.
The study is the third of solanezumab, and involved people with the mildest form of Alzheimer’s. The earlier two trials suggested that people at the earliest stages of the disease seemed to benefit the most in improving some brain skills when they were tested after a year or so on the drug. In this final study, the researchers focused on people with mild disease who showed signs of amyloid, a key factor in Alzheimer’s disease, on brain scans and also had signs of memory and reasoning decline, but still scored higher on mental tests than those with more advanced disease.
Even these people, however, did not show much difference in their cognitive testing scores after more than a year on the drug compared to people who received a placebo. That suggests that even in people with mild disease, the drug was not able to affect the brain deterioration typical of Alzheimer’s. The researchers also measured the amount of amyloid, which builds up in the brain as the disease gets worse, and found no significant changes in the amount of amyloid plaques from the beginning to the end of the study in people who received the drug.
While the results definitively show that the dose used doesn’t help even people with mild disease, it doesn’t necessarily mean that the strategy of attacking amyloid, as solanezumab does, is worthless. Solanezumab is designed to soak up early forms of amyloid protein, before they stick together to form plaques. It’s possible that even in people with mild disease, there is already too much amyloid deposited in the brain, so that even removing the smaller fragments of amyloid will not have much of an effect.
It’s also possible that the dose of the drug wasn’t sufficient to be effective. But the dose is often a balance between effectiveness and side effects; other drugs being tested that remove amyloid from the brain have lead to serious brain swelling.
“Clearly solanezumab at this dose in this population is not effective,” says Dr. Lawrence Honig, professor of neurology at Columbia University Medical Center. “This study cemented that. But does this mean solanezumab might not be a good drug at a higher dose, a different population or both? No. It doesn’t imply that it might be effective at all. That’s being tested.”
Other studies are looking at using solanezumab at a higher dose, and researchers are finding ways to test the drug even earlier in the disease process, perhaps even before symptoms of Alzheimer’s start. Better ways to detect amyloid in the brain are making that possible, and scientists are also testing other amyloid busters, as they’re called, to see if different ways of breaking down amyloid might be more effective.
“Of course it’s disappointing every time a trial does not reach the level of efficacy that would support use in a clinical population,” says Honig, “but personally I think we are getting closer and closer to building a better drug.”