INTRODUCTIONThe Phase 3 trial CLARITY AD found that lecanemab slowed cognitive decline by a statistically significant 27% vs. placebo. However, the subgroup analysis indicated a significant sex difference in the effect, and recent work has implied that lecanemab has either no or limited effectiveness in females. To resolve this ambiguity, we used simulations constrained by the trial design to determine whether the difference could be explained by known sex differences in Alzheimer’s progression, or as an isolated random event.METHODSSimulations were generated using linear mixed models of cognitive decline fit to data from ADNI participants who satisfied CLARITY AD inclusion criteria.RESULTSThe statistically nonsignificant 7.9% sex difference in cognitive decline rate observed in our selected ADNI participants does not explain the trial’s 31% sex difference in lecanemab’s effect. A ≥31% difference occurred randomly in only 12 of our 10,000 simulations, signifying a probability of 0.0012.DISCUSSIONOur results are consistent with those from CLARITY AD. Lecanemab likely affects females and males differently, but we cannot conclude that the drug is ineffective in females.