January 5, 2021
An experimental drug called donanemab showed promise in slowing the decline of Alzheimer’s disease in a medium-size clinical trial. People with Alzheimer’s who received the drug continued to show declines in cognition and in the ability to care for themselves. But the declines were slower than in similar patients who received a placebo, similar treatment but without active drug.
More extensive trials in larger numbers of people would be needed to confirm the effectiveness of the drug. But the findings are notable since so few options are available for treating Alzheimer’s disease. Currently available drugs for Alzheimer’s have limited effectiveness and do nothing to stop the downward progression of disease, and scientists continue to look for new and better treatments.
Donanemab is what is known as a monoclonal antibody, a protein specially designed to recognize a target. In this case the drug targets beta-amyloid, the toxic protein that builds up in the brains of those with Alzheimer’s disease, forming amyloid aggregates and plaques that are believed to disrupt normal brain signaling.
For the study, researchers enrolled 272 patients with mild to moderate Alzheimer’s. Brain scans confirmed the presence in their brains of two hallmarks of the disease: the amyloid plaques, and the tau tangles, the spaghetti-like proteins that accumulate and clump inside neurons as the disease progresses.
Half the patients got an infusion of donanemab every four weeks. The others got a placebo and served as controls.
After 76 weeks, people with Alzheimer’s who took the drug showed 32 percent less decline in tests of memory and thinking skills compared to a control group who got a placebo. Patients taking the drug also showed less decline in measures of day-to-day functioning, like the ability to feed themselves and get dressed.
Patients who got the drug also showed clearing of the amyloid plaques in their brains. Brain scans revealed that the plaques seemed to disappear.
Donanemab also appeared to be relatively safe. Some patients developed some degree of brain swelling, detected on brain scans, though the swelling did not appear to be serious and most importantly did not cause symptoms.
The study’s aim was to test whether “reducing amyloid plaques in Alzheimer’s patients to levels seen in scans of healthy individuals could result in clinically meaningful slowing of cognitive decline,” said Dr. Daniel Skovronsky, the chief scientific officer at Eli Lilly, the drug company that is developing the drug. “The positive results we have obtained give us confidence in donanemab and support its rapid and deep plaque clearance for the potential treatment of Alzheimer’s disease.”
The company is continuing tests of the drug in larger numbers of patients.
The results have not yet been peer reviewed or published in a medical journal, so they are tentative. Many drugs have shown promise in early-stage trials, only to prove mostly ineffective in late-stage trials in large numbers of patients.
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: Eli Lilly.