Lecanemab, an experimental Alzheimer's drug developed by Eisai and Biogen, slowed cognitive and functional decline by 27% compared to a placebo in a new study—results that the drugmakers said were "highly statistically significant."
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Details on the study
Similar to Aduhelm, Alzheimer's drug lecanemab reduces abnormal clumps of beta amyloid, proteins that are typically a sign of Alzheimer's disease.
According to a press release, the study—called CLARITY-AD—enrolled 1,795 patients with mild cognitive impairment caused by Alzheimer's disease, or early-stage Alzheimer's. Roughly a quarter of the participants were Hispanic and African American.
The patients were then tested using the Clinical Dementia Rating sum of boxes (CDR-SB), which measures six domains of cognitive decline with a score ranging from zero to 18, with a higher score meaning more severe cognitive decline.
During the 18 months of the study, patients who received lecanemab performed .45 points better on the CDR-SB than those receiving a placebo, results that the drugmakers said hit the threshold of statistical significance.
According to Ivan Cheung, chair of Eisai's U.S. operations and global head of its Alzheimer's unit, lecanemab's positive effects emerged six months into the trial and were largest at the 18-month point.
The companies also said in the release that lecanemab met its secondary goals of reducing toxic plaques within the brain and slowing decline on three other measures of memory and function.
Around 21% of the participants in the study experienced brain swelling or brain bleeding that was visible on PET scans after taking lecanemab, and less than 3% of those patients had symptomatic cases. According to the companies, those side effects were within expectations.
The study results were released through a press release, and Eisai said it plans to present the full results of the study in November at an Alzheimer's conference in San Francisco.
According to Chueng, the results represented "the first definitively positive large clinical trial to show that you can indeed slow down Alzheimer’s disease at this very early symptomatic stage."
The companies said FDA has agreed the results of the CLARITY-AD trial can serve to verify the clinical benefit of lecanemab, and officials from Eisai said they intend to seek full FDA approval for the drug after they receive an expedited approval.
Experts had mixed reactions to the study results, with some praising the treatment and others saying it didn't produce a significant enough benefit.
"This is a statistically robust and positive study but the treatment effect is small," said Lon Schneider, a physician and Alzheimer's expert at the Keck School of Medicine at the University of Southern California, adding that experts need to take a closer look at the data on lecanemab when it's presented in more detail.
Schneider added that the "relatively low" rates of brain swelling and bleeding "suggest that lecanemab is easier to use" than Aduhelm. In a study published last year in JAMA Neurology, 41% of patients taking Aduhelm were found to have experienced either brain bleeding or swelling.
Michael Greicius, a neurologist at Stanford University who studies and treats Alzheimer's patients, specifically called out the brain swelling in the trial. He believes it could be confounding, as once the side effect presents itself, everyone involved in the trial can be reasonably certain they received lecanemab and not the placebo, which could expose the study results to bias. Greicius added that a real test of the benefits of the drug would look only at lecanemab's effects on patients who did not present the side effect.
"I think if anything this is going to be on the cusp of what's considered minimally clinically significant and it may be below that," Greicius said. "That's where we need to see more data."
Gil Rabinovici, a neurologist at the University of California, San Francisco, said that while "a 27 percent slowing of deterioration seems like a modest effect … for patients with Alzheimer's, this could be very meaningful."
Richard Isaacson, director of the Center for Brain Health at Florida Atlantic University, said the study results are "compelling," adding that he wants to see the full results once they're published. "But in the right patient population at the right time and the right dose, this is a treatment that will probably become a part of the standard of care for patients," he said.
In a statement, the Alzheimer's Association said the study results are "the most encouraging results in clinical trials treating the underlying causes of Alzheimer's to date."
"For people in the earliest stages of Alzheimer's, this treatment has the potential to change the course of the disease in a clinically meaningful way," the association said. "These results indicate lecanemab may give people more time at or near their full abilities to participate in daily life, remain independent and make future health care decisions." (McGinley, Washington Post, 9/27; Garde/Feuerstein, STAT, 9/27; Alltucker, USA Today, 9/27; Robbins/Belluck, New York Times, 9/28; Walker, Wall Street Journal, 9/27)