New Alzheimer's Drug Sharply Reduces Cognitive Decline in Phase 1 Clinical Trial
A new experimental Alzheimer's drug has exceeded scientists' expectations in its ability to reduce amyloid plaque and minimize cognitive decline.
An experimental Alzheimer’s drug has surprised scientists.
While many researchers would have been thrilled to slow the rate of cognitive decline in patients by a mere 20 or 30%, aducanumab greatly exceeded expectations: the drug, being developed by Biogen, slowed the rate of cognitive decline by 70% in its highest dose.
The results of this small but substantive phase 1 clinical trial were presented on Friday at a neurology meeting in France. While the trial was designed to look at safety, not necessarily effect on cognition, it nevertheless reported significant decreases in cognitive decline that corresponded to the amount of the drug administered. It also greatly reduced the amount of amyloid plaque in the patients’ brains, though scientists caution that this does not prove or disprove what’s known as the amyloid hypothesis: the idea that build-up of amyloid proteins leads to dementia in Alzheimer’s disease.
Other companies like Johnson & Johnson and Pfizer have attempted similar drugs but failed to see any positive results. Eli Lilly and Roche are still working on theirs, and some experts believe they could see a bigger impact if the drugs are administered at an earlier stage of the disease’s progression.
Here’s Andrew Pollack, reporting for The New York Times:
Biogen tried to increase its chances of success by treating patients with either mild disease or so-called prodromal disease, an even earlier stage. It also enrolled only patients shown to have plaque in their brains using a new imaging technique. In some trials of other drugs, some of the patients turned out not to have plaque, which could have been a reason the trials were not successful.
The results reported Friday were for 166 patients, who were randomly assigned to get one of several doses of the drug or a placebo. The drug not only slowed cognitive decline but also substantially reduced plaque in the brain, and higher doses were better than lower doses. Those are signs that the effects seen were from the drug.
People who received the placebo scored an average of 3.14 points lower in a 30-point mental state test at the end of the year-long trial than they’d scored in the beginning. But the decrease for those who received the highest dose of the drug was only 0.58 points, and 0.75 points for those who received a medium dose. And on another cognitive and task-oriented test, the placebo group declined by 2.04 points, while the drug recipients worsened only 0.59.
One problem with the highest dose is that it appears to result in a major side effect known as ARIA-E, or a type of localized swelling in the brain. The effect was even more pronounced among patients who have a genetic variant that increases Alzheimer’s risk. It is currently unclear as to whether or not the risks of taking the highest dose will be worthwhile if this drug passes subsequent trials. No one taking the middle dose who also experienced swelling dropped out of the study, which suggests that perhaps a medium or even low dose may be sufficient.
The results from this latest trial may be the most telling yet, even if the sample size is somewhat small and more work needs to be done—for example, in determining what amyloid species are being targeted, and whether or not inflammation plays a larger role in Alzheimer’s than amyloid does. Still, there is hope on the horizon for generations to come.
Photo credit: Maiara Bolsson / Flickr (CC BY 2.0)