Chicago (Reuters): This week, there was clear evidence that Eisai and Biogen’s drug lecanemab slows cognitive decline in early-stage dementia. This has led people who study Alzheimer’s to work toward a tempting goal: stopping dementia before the first signs show up.
Lecanemab is an antibody that goes after and gets rid of dangerous clumps of a protein called amyloid beta that builds up in the brains of Alzheimer’s patients. The companies’ trial with 1,800 people showed on Tuesday that doing this also slows the progression of the disease that kills brain cells.
After 18 months, people with mild cognitive impairment or early-stage dementia who took the drug had 27% less cognitive decline than those who got a placebo.
Dr. Christopher Van Dyck, who runs the Alzheimer’s Disease Research Unit at Yale School of Medicine, said that gives them about six months more to cook, use a computer, or pay their bills.
Scientists have already started to argue about how strong the benefit is. But the results suggest to many people who study Alzheimer’s that it might be possible to stop the decline from happening at all.
“It makes you wonder what will happen if you step in when the brain damage isn’t too bad,” Van Dyck said.
In a trial called AHEAD, Eisai, Biogen, the National Institutes of Health, and the US Alzheimer’s Clinical Trial Consortium are working together to find out the answer to this question. In the global trial, which is taking place at 100 sites, Eisai’s lecanemab is being tested on people who have high levels of amyloid in their brains but are still smart.
“All of a sudden, these results make the AHEAD study seem even more important,” Van Dyck said.
Dr. Reisa Sperling, who is in charge of the trial and runs the Center for Alzheimer’s Research and Treatment at Brigham and Women’s and Massachusetts General Hospitals in Boston, found the results to be especially moving.
Sperling and his team chose lecanemab in 2019 because it was safe and could remove amyloid from the brain, which was shown in an earlier midstage trial. At that time, it wasn’t as clear how well the drug worked.
She said, “I’ve been holding my breath for the last two and a half years, so it was great to see these results.”
Sperling said she knows there is a debate about whether the 27% benefit is enough for people with early-stage disease, but for people who haven’t had any symptoms yet, that would be a big deal.
“If we saw the same slowing at the early stage of Alzheimer’s,” she said, “most people wouldn’t get dementia in their lifetime, or at least a large number of them wouldn’t.”
The AHEAD study, which started in July 2020 with 1,400 healthy adults between the ages of 55 and 80, has two sister trials that are based on how much amyloid is in the brain. Those with lower levels of amyloid will be given treatment less often, while those with higher levels will be given treatment more often.
At first, C2N Diagnostics, a specialty diagnostics company based in St. Louis, checks the blood of volunteers to see if they have amyloid. Those who test positive then have a special brain imaging test to make sure that amyloid is present in their brains.
Sperling said that the number of expensive imaging tests has already been cut in half because of this screening test.
She and her colleagues are also thinking about adding a blood test to look for abnormal forms of a protein called tau that is also linked to Alzheimer’s.
Sperling plans to show at an Alzheimer’s meeting this fall that levels of p-tau217, a type of tau, rise in the blood just as early or even earlier than amyloid in people who are at risk for Alzheimer’s disease but don’t have any symptoms yet.
“From a scientific point of view, this is very important.” “It seems to me that letting amyloid build up changes Tau even before symptoms show up,” she told me.
“A BIGGER EFFECT”
Sperling said that in some people with normal brain function, tau builds up in parts of the brain before there are any signs of brain damage. Some people with high levels of both amyloid and tau that have spread all over the brain are already doing worse on memory tests.
“All of these people have normal thinking skills because they had to have them in order to be in the study. “She told me that if they have both Amyloid-beta and Tau, they are not as normal as people who only have Amyloid-beta.
Sperling thinks that the blood tests will accurately tell if people who don’t have any symptoms of Alzheimer’s disease already have too much amyloid in their brains.
A team at Washington University School of Medicine in St. Louis is testing lecanemab on people with an inherited form of Alzheimer’s dementia along with an Eisai anti-tau agent called E2814.
“There are good reasons to think that the two work together,” said Dr. Randall Bateman, who is leading this trail. “If we can hit both, we’ll have a bigger effect than if we just hit one.”
Sperling’s study found that people whose brains have both amyloid and tau “don’t stay normal for very long.”
She wants to test both anti-amyloid and anti-Tau drugs on people with early Alzheimer’s disease next year. “I think people are at risk once they have even a little tau,” she says.
The COVID pandemic slowed down the sign-up process for the AHEAD trial, which is only a third of the way done. Sperling hopes that the results of the lecanemab trial will get more people to sign up for the study.
She said, “I think we’re on the right track.” “We have to show it now.”