The American pharmaceutical company Eli Lilly announced last week that it had seen encouraging clinical trial results of his new Alzheimer’s medication.
According to the company, their experimental drug, donanemab, was found to slow cognitive decline by 35 percent in a late-stage study.
While these results sound promising, the full data hasn’t been released yet, so there’s still a lot we don’t know.
Donanemab works by targeting a common hallmark of Alzheimer’s disease in the brain: amyloid plaques.
Beta-amyloid is a protein that plays an important role in brain function for everyone. But in patients with Alzheimer’s disease, beta-amyloid becomes toxic — it clumps together and disrupts the connection between brain cells and their function. This leads to cognitive problems such as memory loss.
Donanemab uses the body’s immune system to target and clear these amyloid plaques from the brain, while reducing disease-related decline.
But what’s most important about this new drug is that it only binds to harmful, established plaques, leaving other forms of beta-amyloid alone.
The trial was conducted in 1,182 people with early symptoms of Alzheimer’s disease and detectable plaques in their brains. Half of the participants initially received 700 milligrams of donanemab intravenously every four weeks for the first three doses, then 1400 milligrams every four weeks thereafter. The other half of the participants received a placebo treatment.
Each participant’s duration of treatment was determined by measuring the plaques in their brains. They only stopped treatment when the plaques in their brains were considered gone. Slightly more than half of the participants completed the course after one year.
Another 20 percent of participants completed treatment at 18 months — meaning the drug was able to achieve some level of plaque removal for 72 percent of participants who received donanemab.
Nearly half of the participants who took donanemab showed no signs of an increase in the severity of their disease after one year. By comparison, this was only true for 29 percent of the placebo group.
Importantly, donanemab also slowed clinical and functional decline by 35 percent in all cases of those who took the full course of donanemab, compared to the placebo group.
It was also shown that, compared to the placebo group, participants taking the drug had a 40 percent less decline in their ability to perform daily activities after 18 months, in addition to a 39 percent lower risk of progressing to the next stage of the sickness.
The researchers then focused their further analysis on another 552 patients who had high levels of tau in their brains (a small protein usually used as a marker of the progression and severity of Alzheimer’s disease).
They found that, when the data was combined with participants with intermediate tau levels, cognitive decline was slowed by 22 percent, compared with 35 percent for the first study cohort.
However, the trial also showed that the drug had worrisome side effects. For example, about 24 percent of participants experienced brain swelling, while 31 percent experienced microbleeds.
These side effects were dangerous in about 1.6 percent of cases and led to three deaths.
How it measures
In general, these results do sounds encouraging. But it’s important to note that the full results of the phase 3 trial for donanemab have yet to be published, so it’s best to wait until then to understand more about this drug.
Donanemab is not the first amyloid-targeted drug to be developed. Two other drugs that work by a similar mechanism have been approved for use in recent years. But both have produced slightly different results compared to donanemab.
The first drug, called aducanumab, did lead to a reduction of plaques in the brain. But there was controversy when it came to the trial resultsin that the effectiveness of the drug only became significant when certain subgroups of patients were excluded (or included) from the analysis – such as patients who fell out.
The drug was approved despite the fact that it clinical benefit may be limited.
The other drug lecanemabwhich was approved for use by the U.S. Food and Drug Administration earlier this year was found to reduce both plaques and disease-related decline in early-stage Alzheimer’s disease.
Participants in the lecanemab study had a 27 percent slower rate of cognitive decline after 18 months of treatment. The drug was also found to slow the decline of a measure of daily living by 37 percent after treatment compared to the placebo group.
But while lecanemab had relatively worse outcomes compared to donanemab, it also had a lower percentage of unwanted incidents.
While the results of donanemab may be promising for anyone who has been diagnosed with or is at risk of Alzheimer’s, there’s still a lot researchers don’t know, such as why donanemab seems to work differently in different people.
There are also currently no data showing which patients may benefit most from this treatment. The only exception to this is data showing that patients with less severe disease (as indicated by tau levels and symptoms) benefited more than patients with more severe disease.
This suggests that donanemab may work best when administered to patients with early-stage amyloid plaques.
We also do not yet know which patients are more at risk of developing dangerous side effects, nor whether the use of donanemab in patients without symptoms but with established plaques has a preventive effect. Finally, we also don’t know if and when plaques can reappear, or if these effects are permanent.
Further studies will need to focus on exploring these unknowns, in addition to looking at what makes this treatment successful.
Nevertheless, the results of this study make it clear that early intervention and targeting changes in the right hemisphere at the right time are critical when it comes to Alzheimer’s disease.
Perhaps in combination with screening for Biomarkers for Alzheimer’s riskmay new drugs allow scientists to stop the disease before it starts.