The experimental Alzheimer’s disease drug lecanemab slowed cognitive decline in some people with early Alzheimer’s disease but also caused serious side effects in some patients, according to new results from a late-stage clinical trial.
Lecanemab is in a family of medicines designed to clear the brain of plaques formed by the buildup of a protein known as beta-amyloid, which is thought to play a role in the development of Alzheimer’s disease.
The new results, published November 29 in the New England Journal of Medicine (NEJM), offer a more detailed look at the effectiveness and safety of the drug two months after its developers, the drugmakers Biogen and Eisai, released preliminary findings from this 18-month clinical trial highlighting that lecanemab slowed cognitive decline by 27 percent.
“In persons with early Alzheimer’s disease, lecanemab reduced brain amyloid levels and was associated with moderately less decline on clinical measures of cognition and function than placebo at 18 months but was associated with adverse events,” the researchers wrote in the NEJM report. “Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease.”
For the trial, researchers randomly assigned almost 1,800 people with early Alzheimer’s disease to receive biweekly infusions of lecanemab or a placebo solution. The trial included people with a wide range of chronic health problems, such as obesity, diabetes, and high blood pressure — reflecting the real-life circumstances of many Alzheimer’s disease patients. Participants ranged in age from 50 to 90 years old and had either mild cognitive impairment or mild dementia.
At the start of the trial, participants in both groups had so-called clinical dementia rating scores of about 3.2 out of a possible 18 points, a lower score consistent with early Alzheimer’s disease and “very mild” symptoms.
By the end of the 18-month trial, scores climbed about 1.21 points in the lecanemab group, compared with about 1.66 points in the placebo group. Judging by these scores, lecanemab slowed cognitive decline by 27 percent. The scores also suggest that patients in both groups still had “mild” symptoms of dementia and cognitive decline by the end of the trial.
Advanced brain scans also showed less accumulation of amyloid during the trial for people taking lecanemab. Participants in both groups started with similar average amyloid levels measured by a unit known as centiloids: 77.92 in the lecanemab group and 75.03 in the placebo group. By the end of the trial, amyloid levels declined by 55.48 centiloids on average with lecanemab, but rose by an average of 3.64 with the placebo.
The new trial results also offered a clearer picture of potential safety issues with lecanemab. Researchers reported in the NEJM that about 48 percent of the patients on lecanemab and 22 percent on placebo experienced treatment-related side effects, most often involving reactions related to the infusion process.
There were six deaths in the lecanemab group and seven fatalities in the placebo group during the trial. Researchers wrote in NEJM that the deaths were not treatment related. There have been recent news reports of two patient deaths associated with lecanemab.
With lecanemab, 14 percent of patients experienced serious side effects and 6.9 percent stopped treatment as a result of adverse events. With the placebo, 11.3 percent of patients experienced serious side effects and 2.9 percent discontinued treatment because of adverse events.
Researchers reported more details about a side effect that has been an ongoing concern with medicines targeting amyloid in the brain — the potential for bleeding and swelling known as amyloid-related imaging abnormalities (ARIA). In the lecanemab group, 17.3 percent of participants had ARIA brain bleeding, compared with 9 percent on placebo. And 12.6 percent of patients on lecanemab had ARIA brain swelling, compared with 1.7 percent on placebo.
Brain bleeding and swelling have also been found with the first amyloid-clearing drug, Aduhelm. The U.S. Food and Drug Administration (FDA) approved Aduhelm in 2021 under an accelerated process that required additional testing because it didn’t show a clear clinical benefit. Earlier this year, Medicare, the U.S. health program for people 65 and older, limited coverage of Aduhelm to patients in clinical trials, citing a lack of definitive proof that it improves symptoms.
More than six million Americans have Alzheimer’s disease, and their ranks are expected to swell to 13 million by 2050, according to the Alzheimer’s Association. About one-third of people who have mild cognitive impairment due to Alzheimer’s disease go on to develop full-blown dementia within five years.
There are few effective treatments and no cures.
“Today’s results show that lecanemab slows cognitive decline, which is welcome news for the millions of patients and families living with Alzheimer’s,” said Howard Fillit, MD, a cofounder and the chief science officer at the Alzheimer’s Drug Discovery Foundation, in a statement. “But this is only a start to stopping Alzheimer’s in its tracks. We have a lot of ground to cover to get from the 27 percent slowing lecanemab offers to our goal of slowing cognitive decline by 100 percent.”