Target Occupancy Study (TOS), page-13

This correspondence is dated April 2018:


As to your question about ABT384 – this was an AbbVie 11B-HSD1 inhibitor that was developed as a treatment for diabetes, and as such targeted the enzyme systemically in the liver and adipose tissue. ABT384’s enzyme inhibition alibility isn’t in question, however, when the drug was studied in Alzheimer’s disease, it was quite clear that its brain penetration was inadequate for the purpose. On current published data the estimate is that the amount of ABT384 that crossed the blood-brain-barrier was adequate to inhibit the 11B-HSD1 enzyme in the brain only up to 11%. We know that 30% inhibition of the enzyme is the minimum required. Xanamem, in contrast, crosses the blood-brain-barrier in concentrations that achieve a 50% inhibition of the enzyme, with the 10mg dose used in XanADu