Lecanemab Reduced Cognitive Decline in Early Alzheimer Disease in Confirmatory Trial
In the phase 3 confirmatory Clarity AD trial, participants with early Alzheimer disease who were treated with lecanemab (Eisai, Woodcliff Lake, NJ and Biogen, Cambridge, MA) had improved cognition. Participants in the trial (n=1,795) had mild cognitive impairment (MCI) due to AD or mild AD and confirmed amyloid pathology in the brain. Cognitive improvement was measured with the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Participants in the Clarity-AD study had similar baseline characteristics and 25% were Black or Hispanic/Latinx. All participants were randomly assigned 1:1 to receive 10 mg/kg lecanemab or placebo biweekly.
In the intention-to-treat population, those treated with lecanemab vs placebo for 18 months had a 27% reduction in clinical decline (-0.45 points on CDR-SB; P<.001), with differences between lecanemab and placebo appearing as early as 6 months. Lecanemab treatment also resulted in improvements on other clinical measures of AD, including the AD Assessment Scale-Cognitive Subscale-14 (ADAS-cog14), AD Composite Score (ADCOMS) and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL). Further, statistically significant reductions in brain amyloid were also seen with lecanemab vs placebo.
Haruo Naito, chief executive officer at Eisai said, "The positive result of lecanemab. . . . . .is an important milestone for Eisai in fulfilling our mission to meet the expectations of the AD community. AD not only presents a great challenge for patients and their families, but it also negatively impacts society, including decreased productivity, increased social costs and disease-related anxiety. We believe that helping to alleviate these burdens will positively impact society as a whole. Eisai believes these findings will create new horizons in the diagnosis and treatment of AD as well as further activate innovation for new treatment options. The successful results of the Clarity AD clinical trial would not be possible without the truly inspiring dedication of the study's participants, their families and caregivers and the clinical investigators around the world. We thank all the people involved in the study for their invaluable contributions."
Among those treated with lecanemab vs placebo, amyloid-related imaging abnormalities (ARIA) with edema/effusion (ARIA-E) occurred in 12.5% vs 1.7% and was symptomatic in 2.8% of those treated with lecanemab. ARIA with cerebral micro- or macrohemorrhages and superficial siderosis (ARIA-H) occurred in 17% of those treated with lecanemab vs 8.7% with placebo and was symptomatic in 0.7% with lecanemab vs 0.2% with placebo.
Lecanemab is a monoclonal antibody to amyloid beta (Aβ) protofibrils being investigated for potential treatment of AD. Submission to the Food and Drug Administration (FDA) under the accelerated approval process was completed in July 2022. A Prescription Drugs User Fee Act action date (PDUFA) is set for January 6, 2023, and the FDA has agreed that the results of Clarity AD can serve as the confirmatory study to verify the clinical benefit of lecanemab.
Results of the Clarity AD study will be presented November 29, 2022, at the Clinical Trials on Alzheimer's Congress (CTAD) in San Francisco, CA.