- In the phase 3 Clarity AD trial by van Dyck et al. the primary end point was the change from baseline to 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB; scores range from 0 to 18, with higher scores indicating greater impairment).
CDR-SB Score Changes:
In the phase 3 Clarity AD trial, the primary endpoint was the change in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score from baseline to 18 months. The minimal clinically relevant change in CDR-SB is estimated to be 1-2 points. At 18 months, the CDR-SB score increased from baseline by 1.21 points with lecanemab and by 1.66 points with placebo, resulting in a significant between-group difference of -0.45 points.
Sex Differences in Efficacy:
Concerns were raised about the possible lack of therapeutic efficacy among women in the trial. Among men, the between-group difference in CDR-SB score change was -0.73, which appears significant, whereas among women, the corresponding difference was only -0.20 (apparently not significant).
Unblinding and Adverse Events:
The Clarity AD trial results could have been influenced by unblinding due to adverse events. More patients in the lecanemab group experienced infusion-related reactions (26.4% vs. 7.4%) and amyloid-related imaging abnormalities with edema or effusions (ARIA-E) (12.6% vs. 1.7%). The trial did not use more objective scales, such as the Mini–Mental State Examination, as a measure of cognition.
ApoE ε4 Homozygotes:
In a subgroup of apolipoprotein E (ApoE) ε4 homozygotes, the effect of the drug was +0.28, which is larger in magnitude than the beneficial adjusted mean score among all women who received lecanemab (-0.20). The authors could provide ApoE genotype breakdowns for patients who left the trial and report results of the CDR-SB cohort analysis with only the patients who had no adverse reactions to antiamyloid agents.
New England Journal of Medicine. (2023). Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine, 388(17), 1630-1632. doi:10.1056/NEJMc2301380