August 9, 2023
An experimental drug for Alzheimer’s showed promise in slowing declines in thinking and memory skills when given early in the course of the disease, according to a new report. The findings are a reminder that researchers continue to investigate promising new drugs for Alzheimer’s, and that treatments for the disease may be most effective when given early in the course of the illness, when symptoms are milder and damage to the brain is less extensive.
Much of the attention around Alzheimer’s treatments has focused on new drugs like Leqembi, which was approved by the Food and Drug Administration earlier this year. But this new drug, called donanemab, showed similar benefits in helping to slow declines in cognition and the ability of people with Alzheimer’s disease to care for themselves.
The benefits were modest, and the drug is not a cure. In addition, the new drug also had some potentially serious side effects. But the results were encouraging and underscore the continued need for research into new therapies that can effectively treat Alzheimer’s disease.
Donanemab, like Leqembi, is what is known as a monoclonal antibody, a protein specially designed to recognize a specific target in the body. Both drugs target beta-amyloid, the toxic protein that builds up in the brains of those with Alzheimer’s disease. Toxic beta-amyloid forms amyloid aggregates and plaques, which are believed to disrupt normal brain signaling, and both monoclonal antibodies help to clear these build-ups. Also, like Leqembi, donanemab is given by infusion.
For the study, published in the journal JAMA, researchers studied 1,736 men and women in the early stages of Alzheimer’s disease, when declines in thinking and memory skills are somewhat modest. All had evidence of the telltale plaques of Alzheimer’s in their brains, as well as tau tangles, the spaghetti-like proteins that accumulate and clump inside neurons as the disease progresses.
After 18 months, donanemab slowed declines in thinking and memory skills by about four-and-a-half to seven-and-a-half months compared to study participants who were receiving a placebo drug. Benefits were most pronounced in those with the mildest symptoms, in people younger than 75, and in those with the lowest levels of tau in their brains. Patients who got the drug also showed clearing of the amyloid plaques in their brains.
The findings highlight earlier research showing that Alzheimer’s treatments may be most effective when given early in the course of the disease, when damage to the brain is less extensive. Therefore, early diagnosis and early treatment may be most effective for managing Alzheimer’s disease, many experts believe.
Donanemab and Leqembi have not been compared side-to-side in studies, and the design of this study was different than trials that were carried out to test Leqembi. So it is hard to say at this point which drug might be more effective.
Both drugs also carry the risk of swelling and bleeding in the brain, which can be life-threatening, so patients must be monitored closely. Doctors and patients must carefully weigh the benefits and risks of giving the drugs.
Importantly, neither drug can reverse or repair damage to the brain that has already occurred, and benefits are modest and may not be noticed by family members. But after nearly two decades in which no new Alzheimer’s drugs were available, these findings offer hope.
The current study was a Phase 3 trial, a late-stage study in a large number of patients. Lilly, the drug company that makes donanemab, is seeking approval from the Food and Drug Administration, which would make the drug available for doctors to prescribe.
By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Eric Schmidt, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.
Source: John R. Sims, MD; Jennifer A. Zimmer, MD; Cynthis D Evans, PhD; et al: “Donanemab in Early Symptomatic Alzheimer Disease The TRAILBLAZER-ALZ 2 Randomized Clinical Trial.” JAMA July 17, 2023