Results of an 18-month trial led by U.S. pharmaceutical producer Eli Lilly have shown its new Alzheimer’s drug can delay the progression of the disease by up to 35.1 percent.
That means across the trial certain patients had their decline slowed down by 4.4 to 7.5 months.
It’s expected that the drug, called Donanemab, will be approved by the U.S. Food and Drug Administration (FDA). This will make it the third medication available to treat the debilitating condition in the U.S.
However, the trial also showed that there were severe side effects that came with the treatment – and the results make it clear that the medication is mostly effective for those in the early stages of the disease.
More than 6 percent of the 860 patients who received Donanemab infusions experienced symptoms associated with brain bleeds and swelling, such as confusion, headaches and seizures. There were also 3 deaths thought to be related to treatment.
Still, the fact that we have a third potential treatment for this devastating disease after decades of making little clinical progress is an exciting step forward.
This “may prove to be just the opening chapter in a new era of molecular therapies for [Alzheimer’s disease] and related neurodegenerative disorders,” write doctor Gil Rabinovici and neuroscientist Renaud La Joie, both from the University of California, San Francisco.
Neither researcher was involved in the trial, but commented on the results in an accompanying editorial in the Journal of the American Medical Association (JAMA).
Donanemab is an anti-amyloid monoclonal antibody created by Eli Lilly and Company. It works by attacking amyloid-beta proteins in the brain, and is the same type of drug as the other two approved Alzheimer’s treatments: Aducanumab and which was approved in 2021, and Lecanemab which was approved in January this year.
The build-up of amyloid-beta is closely linked to the progression of Alzheimer’s disease. Though debated, the currently leading amyloid cascade hypothesis of the disease suggests that getting rid of the amyloid plaques will help treat the condition.
To test whether this was the case, the Phase 3 Donanemab trial took 1,736 patients and randomly put them into two groups that received an unknown intravenous infusion, consisting of either Donanemab or a placebo, every 4 weeks for 72 weeks.
The patients were tested at the start and end of the trial and ranked on both the integrated Alzheimer Disease Rating Scale (iADRS) and the Clinical Dementia Ratin Scale (CDR-SB).
They also underwent scans throughout the experiment to identify levels of amyloid-beta plaques and abnormal tau proteins in their brains.
This trial is unique because it broke down the trial groups into those with either low/medium or high tau pathology – it’s generally thought that high tau pathology is associated with more advanced Alzheimer’s.
Analysis revealed disease progression slowed by more than 20 percent among those given doses of Donanemab compared to those given a placebo. When analysis was restricted to individuals with low/medium tau pathology, the progress was stalled by 35.1 percent, ased on the iADRS.
Impressively, 47 percent of the low/medium tau group who received Donanemab had no change at all in their CDR-SB rating after one year, compared to only 29 percent of those who received the placebo.
Unfortunately, no significant improvement was seen for the high tau group when compared with the placebo.
Throughout the trial, if any patient had a high enough clearance of amyloid-beta plaques, they were unknowingly moved off the drug and onto the placebo – a move intended to save money and unnecessary treatment. This occurred in 52 percent of the low/medium tau patients in the test treatment group.
What’s interesting is such significant clearance of amyloid-beta plaques could be associated with relatively mild clinical impact, once again highlighting how much we still have to learn.
“These results serve to highlight the complexity of Alzheimer disease itself,” write a group of doctors based in the U.S. who weren’t involved in the trial but commented on the results in JAMA.
“The exceptional ability of drugs such as Donanemab and Lecanemab to remove amyloid, paired with their rather subtle effect on the rate of decline in cognitive and functional measures, suggests that amyloid is likely not the only factor that contributes to Alzheimer disease progression.”
It’s important to note there are some big limitations to the study – almost all of the participants were white, and the age of participants was restricted to between 60 and 85.
The trial also ended after 18 months, although the researchers say an extension is now in the works.
More data is needed before we can tease out exactly who Donanemab will most benefit and whether the potential side effects will be worth it. As Rabinovici and La Joie explain in their editorial, it’s likely that we’ll have better drug options in the future.
But for now, any hope is meaningful for people hoping to delay Alzheimer’s disease just a few more months or years.
The results have been published in the Journal of the American Medical Association.