Is lecanemab really a breakthrough drug for Alzheimer's?
Esteban Pardo | Fred Schwaller
November 30, 2022
Lecanemab appeared to slow progression of the disease in a phase three Alzheimer's drug trial. But is the drug as effective as hoped?
There's news in the world of Alzheimer's research.
In a phase three trial, drug companies Biogen and Eisai reported this week that lecanemab, an experimental monoclonal antibody, reduced cognitive decline caused by the disease by 27% after 18 months.
Researchers have been scrambling to find a treatment for Alzheimer's for decades. Where do these new results put us in the global race to cure this devastating degenerative disease?
What do we know?
Around 2,000 people with early-onset Alzheimer's took part in the trial, which started in March 2019. Half of the participants were given two injections per week of lecanemab, while the others received a placebo.
At the start and end of the trial, researchers measured the severity of the participants'dementia symptoms. After 18 months, the treatment group had a 27% reduction in these symptoms compared to those who received a placebo.
"It is extremely encouraging to see positive effects of lecanemab in a trial of just 18 months. This trial proves that Alzheimer's disease can be treated," Bart De Strooper, director of the UK Dementia Research Institute, told reporters.
Amyloid proteins and Alzheimer's
Like all drugs that end in "mab," which stands for monoclonal antibody, lecanemab is an antibody and specifically targets the amyloid-beta protein.
Humans naturally produce the amyloid-beta protein — it is encoded in a gene in our chromosome 21, one of the 23 pairs of chromosomes in the human body.
When too many of these proteins accumulate in the brain, they can form plaques, which causes neurons in the brain to die. Over time, this causes dementia symptoms in patients with Alzheimer's.
Lecanemab works by helping the body to clear these plaques. The drug sticks to amyloid proteins in the brain, attracting immune cells to break down the plaques. By removing plaques in the brain, fewer neurons in the brain die, thereby slowing down the rate of cognitive decline.
"The full trial data confirms that treatment with lecanemab clearly removes amyloid protein deposits from the brain in a period of months and also has beneficial effects on other hallmarks of Alzheimer's disease," said De Strooper.
Efficacy, safety of lecanemab debated
However, scientific communities are closely monitoring the benefits of lecanemab for patients with Alzheimer's.
Some say the drug did not halt cognitive decline but merely slowed it, and had a questionable impact on symptoms.
Rob Howard, professor of old age psychiatry at University College London, said the treatment benefits were extremely small.
"Lecanemab was associated with a 1.4 point advantage on the ADAS-cog14 (a 90-point scale used to measure memory, attention, language function and other thinking abilities). This is just too small a difference to be noticed in an individual patient," he said.
What's more, many patients experienced severe side effects to lecanemab during the trial. Brain scans showed 17% of participants had brain bleeds, and 13% had brain swelling. And 7% of participants had to stop the trial due to side effects.
Howard suspects the drug won't be taken up widely with health care systems around the world, but was upbeat about the prospects of building on the trial's success.
"We need to keep looking for better and safer dementia treatments and today's results show that we are now on a believable path to doing so," he said.
A long way to go before Alzheimer's cure
Alzheimer's is a devastating and so far incurable disease that impacts more than 50 million people globally, according to data from the BrightFocus Foundation, which funds scientific research on Alzheimer's.
So far, there are still no treatments available to patients that can stop or reverse the progression of the disease. And though the results of this trial seem encouraging, the drug is yet to go through administrative approval*.
Researchers have cautioned against overselling the results before more research has been conducted.
"The trial results have shown us that there is a risk of side effects," said John Hardy, a group leader at the UK Dementia Research Institute at University College London, who was not part of the study.
"This doesn't mean the drug can't be administered, but that it will be important to have rigorous safety monitoring in place for people receiving lecanemab, and further trials to fully understand and mitigate this risk."
Edited by: Tamsin Walker
This article was originally published on September 30 and updated November 30.
Update January 11, 2023:
On January 6, 2023, the U.S. Food and Drug Administration (FDA) approved lecanemab for patients in the earliest stages of the disease. Eisai and Biogen also applied for full approval by the FDA. Eisai has also submitted a marketing application to the European health regulator for review of lecanemab.