September 9, 2015
New data on two drugs in development, solanezumab and aducanumab, continue to raise hopes that new, more effective, drugs might become available for treating Alzheimer’s disease. Drugs that act in new ways are urgently needed because current drugs for Alzheimer’s may ease symptoms for a time but do nothing to stop the disease from progressing. It is hoped that such drugs may actually modify the disease’s course, slowing or even halting Alzheimer’s in its tracks.
The experimental drugs zero in on beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer’s. As levels of beta-amyloid rise, it clumps to form hard plaques in areas of the brain critical for memory and thinking. And as plaques spread, symptoms of dementia become increasingly apparent.
Alzheimer’s is a progressive illness that is thought to begin 10 to 20 years before the onset of symptoms, like memory loss. Experts have been hopeful that drugs like solanezumab and aducanumab that are aimed at stemming the disease’s progression may be most effective when given at an early stage of the disease, before damage to the brain becomes extensive.
But so far, studies have failed to show that such drugs are effective in stopping the declines in memory and thinking skills that are a hallmark of Alzheimer’s disease.
Two earlier studies of solanezumab, made by the drug maker Eli Lilly, did not show that it helped people with moderate Alzheimer’s. But there were hints that it might benefit people in the earliest stages of the disease. The company began a large new trial of the drug in people with mild disease, with results expected in 2017.
The new data comes from a follow-up from the older solanezumab trials, in which study participants were given the option of continuing on the drug for an additional two years. In the original studies, which lasted for 18 months, some of the participants were given solanezumab, while others were given a look-alike treatment. Neither doctors nor patients knew who was getting which.
In the follow-up, everyone was taking the actual drug, solanezumab. Some of the study participants were taking it continuously for several years, while others only began taking it in the follow-up phase, since they were getting a dummy pill originally.
What the researchers found was that those who were taking solanezumab for several years showed less decline in tests of memory and thinking skills and the ability to carry out day-to-day tasks than those who were started on the drug only after the older studies ended. The findings suggest that the drug has a clinically significant effect, since those taking it for longer periods seemed to have greater improvements in cognition.
The findings were presented at a medical conference and published in the journal Alzheimer’s and Dementia: Translational Research & Clinical Interventions.
New data on aducanumab, made by Biogen, was also presented at the conference. The drug had sparked hopes earlier this year, when researchers reported that the higher the dose of drug, the less people with Alzheimer’s declined on tests of memory and thinking skills. Researchers also found that treatment with aducanumab resulted in a significant reduction in plaque buildup in the brain; the higher the dose and the longer the drug was given, the greater the reduction in plaque. The brains of those getting a placebo were virtually unchanged.
But the highest dose of the drug produced brain swelling in a high percentage of those taking it. This potentially serious side effect is a worry for doctors. The new data involved 30 study participants who had gotten a medium dose of the drug.
What the researchers found was that the medium dose of aducanumab produced some improvements in certain measures of memory and thinking compared to those getting a low dose of the drug. The drug still produced some side effects at the medium dose, though they were not serious, and research on the drug will continue.
Researchers are hoping that these new drugs may ultimately prove to have benefits for those in the earliest stages of Alzheimer’s, but there is no guarantee of success. Other drugs have shown promise in early trials, only to show no effectiveness in larger late-stage studies. Nevertheless, any beneficial effects of these drugs could mean that other drugs that lower beta-amyloid, the substance that forms plaques in the brains of those with Alzheimer’s, might be effective in treating Alzheimer’s.
More research to understand what causes Alzheimer’s, and how it might be treated, is critical for finding a cure for a disease that is estimated to affect more than 25 million people worldwide.
Source: Eli Lilly and Company, Biogen, Alzheimer’s Association International Conference, Washington, D.C July 2015.