An experimental drug called lecanemab is getting attention after clinical trial results show that it appears to slow progression of Alzheimer’s disease, a major milestone in the fight against the deadly and progressive disease.
The companies behind the drug—Biogen and Eisai—revealed in September that lecanemab reduced both cognitive and functional decline in patients by 27% in their phase 3 clinical trial. Now, the trial results have been published in the New England Journal of Medicine. But, while the study’s researchers note in the conclusion that lecanemab “reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo,” they also pointed out that it was “associated with adverse events.” Meaning, it had some side effects worth noting (more on those in a moment).
As a result, they wrote, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease.”
Nearly 6 million Americans have Alzheimer’s disease, and that’s a number that’s expected to rise, according to the Centers for Disease Control and Prevention (CDC). Alzheimer’s disease is the sixth leading cause of death in the country, and there is currently no treatment to stop its development or progression to severe stages.
So, will lecanemab potentially be helpful in the fight against Alzheimer’s disease or not? Here’s what the study found—and what doctors think.
What did the study find?
According to the study, a phase 2 clinical trial did not find a significant difference in results between lecanemab and a placebo in patients over 12 months. However, the phase 3 trial found that lecanameb was linked with less cognitive decline and more clearance of amyloid plaques (protein fragments associated with Alzheimer’s disease) after 18 months.
The phase 3 clinical trial was done at 235 different medical sites across North America, Europe, and Asia from March 2019 through March 2021. The trial included 1,795 adults between the ages of 50 and 90 who had mild cognitive impairment due to early Alzheimer’s disease or mild Alzheimer’s disease-related dementia. Study participants were randomly assigned to received lecanemab via IV infusion every two weeks or a placebo.
Study participants in both groups had a clinical dementia rating (aka a CDR-SB score) of around 3.2 when the trial began. (A higher number is linked with more cognitive impairment.) At the end of the 18-month trial, the score rose 1.2 points in the group that received lecanemab; It went up nearly 1.7 points in the placebo group.
The study also tracked average amyloid levels: In the beginning, the average amyloid level was 77.92 centiloids in the group of participants who took lecanemab and 75.03 centiloids in participants who took a placebo. At the end of the trial, the average levels went down to 55.48 centiloids in the lecanemab group, but actually went up 3.64 centiloids in the placebo group.
“There is a major unmet need for treatments that can slow the progression of Alzheimer’s disease, since the treatments in current use only provide temporary symptomatic benefit,” says lead study author Christopher H. van Dyck, M.D., director of the Alzheimer’s Disease Research Center at the Yale University School of Medicine.
The Alzheimer’s Association released a statement applauding the findings, and called on the Food and Drug Administration (FDA) to accelerate approval of the drug.
“These peer-reviewed, published results show lecanemab will provide patients more time to participate in daily life and live independently,” the statement reads. “It could mean many months more of recognizing their spouse, children, and grandchildren. Treatments that deliver tangible benefits to those living with mild cognitive impairment (MCI) due to Alzheimer’s and early Alzheimer’s dementia are as valuable as treatments that extend the lives of those with other terminal diseases.”
Lecanemab side effects
A big sticking point with lecanemab is the side effects. The trial results point out that the drug led to “infusion-related reactions” in more than 26% of patients and “amyloid-related imaging abnormalities” with edema (i.e. swelling) or effusions (fluid leaking into a body cavity) in 12.6%.
More than 17% of those who took lecanemab experienced brain bleeding, compared to 9% of those in the placebo group. Nearly 7% of people in the lecanemab group stopped taking the drug due to side effects; only about 3% of people in the placebo group did the same.
Overall, there were six deaths in the lecanemab group and seven in the placebo group, which translated to 0.7% of lecanemab participants and 0.8% of placebo participants.
What do doctors think?
Experts say there is a need for an Alzheimer’s treatment like this. “There are currently drugs available for the treatment of Alzheimer’s disease, but they do not modify the disease progression,” says Jamie Alan, Ph.D., associate professor of pharmacology and toxicology at Michigan State University.
Douglas W. Scharre M.D., professor of clinical neurology and psychiatry, and director of the Center for Cognitive and Memory Disorders at The Ohio State University Wexner Medical Center said he’s “very excited to hear of the positive clinically significant results.” He adds, “finally, a bit more hope to help those with Alzheimer’s disease.”
“This is big news,” says Scott Kaiser, M.D., geriatrician and Director of Geriatric Cognitive Health for the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, Calif. “Lecanemab clearly demonstrated some benefit, but there are still remaining questions as to how clinically significant that benefit will be and open questions with risks for patients.”
The side effects of lecanemab have gotten attention, but Dr. Scharre said that the overall safety profile of the drug is “reasonably good,” noting that it’s “much improved” over aducanumab, a controversial medication that was approved by the FDA to try to slow the progression of Alzheimer’s disease. “Only about 7% had to stop taking the medicine due to adverse events compared to about 3% who were on placebo. That means 93% tolerated the medicine well enough,” Dr. Scharre says. “There were six deaths in the lecanemab group and seven in the placebo group. So, there is no real difference.”
Alan points out that “the most common side effects are infusion reactions,” adding that “this isn’t particularly bothersome to me, as these occur with other antibody-based therapies.” She also notes that “no deaths were thought to occur because of the drug.”
But, Alan says, there is a cost-benefit ratio to consider. “Some of the side effects were brain bleeds, which can potentially result in more cognitive or physical decline,” she says.
If lecanemab is eventually approved by the FDA, Dr. Scharre says it will be important for patients to take it sooner rather than later. “Since this medication only helps those with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s dementia, it is critical for people to get into their provider as soon as they or their family notice a change in their cognition, memory, or thinking over a year’s time,” he says. “If individuals are not identified in the early stages of Alzheimer’s, they will miss the opportunity and window for treatment using these agents as those individuals will be identified too late.”
What happens next with lecanemab?
The makers of the drug said in a press release that they are hoping to file to have lecanemab approved by the Food and Drug Administration (FDA) before April 2023. The FDA has already granted the drug “priority review,” meaning the FDA wants to take action on it within six months.
Dr. Kaiser says that a drug like lecanemab is “needed and shows promise.” Still, he urges people to “focus on prevention” of Alzheimer’s, including exercising regularly, eating a healthy diet, and trying to keep high blood pressure under control.
You Might Also Like