New Alzheimer’s drug shows 35% reduction in cognitive decline in late-stage clinical trial : ScienceAlert

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U.S. pharmaceutical company Eli Lilly last week announced promising clinical trial results for a new Alzheimer’s drug.

The company says its experimental drug, donamab, was shown in a late-stage study to slow cognitive decline by 35 percent.

While these results sound promising, there are still many unknowns as the full data have not yet been published.

Donanemab works by targeting amyloid plaques, a common hallmark of Alzheimer’s disease, in the brain.

Beta-amyloid is a protein that plays an important role in brain function in everyone. But in Alzheimer’s patients, beta-amyloid becomes toxic, clumping together and disrupting the connections between brain cells and their function. This leads to cognitive problems such as memory loss.

Donanemab can harness the body’s immune system to target and remove these amyloid plaques from the brain, while also reducing disease-related decline.

But the most important thing about this new drug is that it only binds to harmful established plaques, leaving other forms of beta-amyloid alone.

The trial included 1,182 people with early symptoms of Alzheimer’s who had plaques detected in their brains. Half of the participants received 700 mg of donanemab intravenously every 4 weeks for the first three doses, followed by 1,400 mg every 4 weeks. The other half of the participants received placebo treatment.

The duration of treatment for each participant was determined by measuring plaques in the brain. They stopped treatment only when the plaques in the brain were deemed cleared. Just over half of the participants completed their course of treatment one year after her.

An additional 20% of participants completed treatment after 18 months. This means that the drug achieved some level of plaque clearance in 72% of participants who received donanemab.

Nearly half of the participants who took donanemab showed no signs of increased disease severity after one year. In contrast, this was true for only 29 percent of the placebo group.

Importantly, donanemab was also shown to slow clinical and functional decline by 35 percent compared to the placebo group in all cases of patients who received all courses of donanemab.

Participants who took the drug also had 40 percent less decline in their ability to perform activities of daily living and a 39 percent lower risk of progressing to the next stage of the disease at 18 months compared to placebo. was also shown.

The researchers then focused further analysis on an additional 552 patients with high levels of tau (a small protein commonly used as a marker of Alzheimer’s disease progression and severity) in their brains.

They found that when the data were combined with participants with intermediate tau levels, cognitive decline slowed by 22 percent compared to 35 percent in the initial study cohort.

However, the trial also showed that the drug had worrisome side effects. For example, approximately 24 percent of participants experienced brain swelling and 31 percent experienced microbleeds.

These side effects were dangerous in about 1.6% of cases and 3 died.

Measuring method

Overall, these results certainly seem promising. However, it is important to note that the full results of the Phase 3 trials of donamab have not yet been published. So it’s best to wait until then to understand more about this drug.

Donamab is not the first amyloid-targeted drug to be developed. Two other He drugs that act using a similar mechanism have been approved for use in the past few years. However, both of these gave somewhat different results compared to donamab.

The first drug called aducanumab led to a reduction in plaques in the brain. However, there have been controversies regarding the trial’s results, to the point that the efficacy of the drug only became significant when certain subgroups of patients were excluded (or included) from the analysis, such as those who dropped out. There was a discussion in

The drug continued to be approved despite potentially limited clinical benefit.

Another drug, lecanemab, was approved for use by the US Food and Drug Administration earlier this year and was shown to reduce both plaques and disease-related decline in early Alzheimer’s disease.

Participants in the lecanemab trial experienced a 27 percent slower rate of cognitive decline after 18 months of treatment. The drug was also shown to slow the decline in measures of daily living after treatment by 37 percent compared to the placebo group.

However, lecanemab performed relatively poorly compared with donanemab, but also had a lower rate of adverse events.

Donanemab’s results may be encouraging for people diagnosed with or at risk of Alzheimer’s disease, but there are still many things researchers don’t know, including why donanemab’s effects seem to vary from person to person. be.

There are also no data at this time to indicate which patients would 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 those with more severe disease.

This suggests that donamab may be most effective when given early in patients with amyloid plaques.

We also don’t yet have a way to know which patients are at higher risk of developing dangerous side effects, or whether using donemab in asymptomatic patients with established plaques works prophylactically. . Finally, we also do not know if and when plaques will return, or whether these effects are permanent.

Future research should focus on investigating these unknowns as well as examining what makes this treatment successful.

Nonetheless, the results of this trial revealed the importance of early intervention and timely targeting of changes in the right brain when it comes to Alzheimer’s disease.

In fact, perhaps combined with screening for Alzheimer’s disease risk biomarkers, scientists may be able to stop Alzheimer’s disease before it develops with new drugs.

Eleftheria Kodsaki, Neuroimmunology Research Fellow, Cardiff University

This article is republished from The Conversation under a Creative Commons license. Please read the original article.

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