"The absence of any effect at one year is puzzling. It would have been reassuring to see at least a trend for benefit at one year, even if non-significant."

There is actually an effect. In both the mild and high risk groups, there was an improving trend over the whole two years. It is the first year trend of the placebo group that needs explanation. Bear has given one possible and plausible explanation for that and maybe there are more. It is hard to say there is no effect when it improved from 18 to over 20 in the first year. We don't know how much was inproved standard of care and how much was Apabetalone but saying no effect is harsh. If you want to claim no effect, than why would we credit APL for the second year improvement when it was almost the same rate of improvement. There are some unknowns here but hard to say no effect.