You can't realistically discuss "how to do drug pricing in general" without taking into account the dynamic where companies recoup their research costs on a tiny number of hit drugs. It doesn't work if those hit drugs only make a small margin.
Americans are just fatter.
Is your theory that demand is higher in the US and that's why the prices are higher?
I don't see any reason to think that would be the case for a product that is very easy to transport globally. That is, absent other effects, like regulation and the differences between how insurance works in different places, I think this would be a global market with prices driven by global demand.