The investigational drug lecanemab slowed clinical decline in participants with early-stage Alzheimer’s disease by 27% after 18 months of treatment compared with participants who received a placebo, a phase 3 clinical trial has reported.
The results of the “Clarity AD” trial of 1,795 participants were published Jan. 5 in the New England Journal of Medicine.
Based on this finding, the Food and Drug Administration gave the drug accelerated approval on January 6.
“This is truly the first time we have found unequivocally positive results for a potential therapy that may slow the course of Alzheimer’s disease,” said Yale’s Christopher van Dyck, MD, lead author of the paper.
Van Dyck is professor of psychiatry, neurology, and neuroscience and director of the Alzheimer's Disease Research Unit and director of the Division of Aging and Geriatric Psychiatry at Yale.
Lecanemab, developed by Eisai Co., Ltd of Tokyo and Biogen Inc. of Cambridge, Mass, is an antibody treatment designed to attack the most toxic forms of the amyloid-beta protein —a hallmark of Alzheimer’s disease. Individuals who received lecanemab showed a statistically significant reduction in amyloid burden in PET scan sub-study and most lecanemab-treated participants had normal levels of amyloid at the end of the trial.
They also had significant slowing of decline on key secondary measures of cognitive function (26%) and activities of daily living (37%) compared to those who received a placebo. Clinical benefit was evident as early as six months after treatment started and continued through the 18-month duration of the trial.
This is truly the first time we have found unequivocally positive results for a potential therapy that may slow the course of Alzheimer’s disease.
Christopher van Dyck, MD
The most common adverse events in the lecanemab group were infusion-related reactions in 26.4% of participants (compared with 7.4% among those in the placebo group). Infusion reactions — which typically involved transient flushing, chills, fever, rash, and body aches — were largely mild to moderate (96%) and typically occurred on the first dose (75%). Lecanemab was also associated with amyloid-related imaging abnormalities with edema or effusions (a leakage of fluid that accumulates in the brain and is detected on MRI scans), which occurred in 12.6% of lecanemab participants (compared with 1.7% in the placebo group). In addition, lecanemab was associated with amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (blood that is deposited on the surface of the brain and is detected on MRI scans) in 17.3% of lecanemab participants (compared with 9% in the placebo group).
In July 2022, Eisai applied for accelerated approval by the U.S. Food and Drug Administration for the use of lecanemab in early-stage Alzheimer’s disease based on robust plaque clearance in the phase 2 study. Having received the January 6 accelerated approval, the company is now seeking a traditional approval.
Van Dyck said that while lecanemab is not a cure for Alzheimer’s disease, the trial participants who received the drug did experience a preservation of abilities compared with those who received placebo. If the same rates of decline in daily functioning and cognition persisted beyond the 18-month trial period, then those who received the drug may not experience the same loss of daily functioning and cognition experienced by individuals in the placebo group until about seven months later.
“This is an important slowing of decline, but what we next want to know is whether earlier intervention can produce a larger benefit,” van Dyck said. He said trials are underway to determine whether administration of the drug to asymptomatic individuals with an early buildup of amyloid might preserve cognitive health even more.
He presented the efficacy results of the trial Nov. 29 at the Clinical Trials on Alzheimer’s Disease meeting in San Francisco.
Van Dyck is a paid consultant to Eisai, which funded the trials.