OBJECTIVES: The Dependence Scale (DS) captures a combination of the cognitive, functional, and psychiatric changes that occur in Alzheimer’s disease (AD) and is strongly correlated with cost of patient care. As reported previously, combination therapy with donepezil and 35 mg intepirdine (RVT101), an oral 5HT6 antagonist in development for the treatment of mild-moderate AD, was projected based on a conversion algorithm to reduce progression in Dependence Level (DL) compared to donepezil monotherapy using data from a placebo-controlled study. Here we examine potential cost differences associated with this reduced DL progression. METHODS: The Alzheimer’s Disease Cooperative Study – Activities of Daily Living Scale (ADCSADL) was measured in a 48week study of intepirdine vs placebo on top of stable donepezil in subjects with mild-moderate AD (n=684). The ADCSADL was converted to DL using a published algorithm. Total costs were estimated from the Predictors 2 study using self-reported data and assigned to this study. Costs associated with both direct medical and non-medical care were included. Informal caregiving costs were not included. Cost changes from baseline were compared between treatment groups. RESULTS: Estimated costs were higher at more severe DLs, ranging from $4,755 for DL=0/1 to $23,311 for DL=4/5. Costs associated with the donepezil monotherapy group were projected to increase by $595 over all visits, while costs associated with the 35 mg intepirdine plus donepezil combination therapy group were projected to decrease by $283. The magnitude of annual cost benefit associated with intepirdine treatment was projected to range from $443 to $1,203 based on baseline DL. CONCLUSIONS: In this analytical framework, combination therapy with 35 mg intepirdine and donepezil was associated with projected annual cost benefits between $443 and $1,203 compared to donepezil monotherapy. Intepirdine is currently being evaluated in a global Phase 3 study in mild-moderate AD with data expected in 2017.