[pdeuchler]

> All this stuff you here about “evergreening” is entirely the result of gaming the FDA approval practices

Evergreening has absolutely nothing to do with the FDA and everything to do with the USPTO and the specific chemical makeup of insulin, which has unique characteristics that make it very easy to engage in effective "evergreening". This also allows drug companies to manipulate pricing lists in deceptive ways that fool both doctors and distributors into placing higher cost (but chemically identical) products onto "preferred" prescription lists of insurance companies. There are also current court cases where there are accusations of fraud and illegal kickbacks around those practices.

[rayiner]

> Evergreening has absolutely nothing to do with the FDA and everything to do with the USPTO and the specific chemical makeup of insulin, which has unique characteristics that make it very easy to engage in effective "evergreening"

I’m very curious what you think these are.

[nate_meurer]

The best answer comes from the paper you cited earlier:

> "New biologic drugs are orders of magnitude larger than small-molecule drugs, and it’s often impossible to know on an atom-by-atom basis whether one large-molecule drug is the same as another. Subsequent versions of off-patent biotech drugs are therefore called biosimilar rather than generic. Differences in the tissue systems that produce them can lead to differences in protein folding and glycosylation, which could theoretically result in efficacy or safety differences. But the FDA, the EMA, and the generic drug industry hope these issues can be addressed by new regulatory sciences of biosimilarity."

> "Although regulatory pathways for biosimilar insulin are being finalized in the United States and Europe, economists warn that the introduction of biosimilars may not lead to price reductions equivalent to those seen with typical generic medicines. Even an abbreviated approval process for biosimilars will require substantially more original data than the typical abbreviated new drug application required for small-molecule generics and will necessitate immunogenicity and other safety studies in humans."

[nate_meurer]

Sorry, I realize those excerpts in my earlier comment don't really convey what I intended. The paper does talk about about how the various improvements over the years were changes in just a few (or even just one) amino acids in the molecule. It's a large molecule, nearly 6000 daltons (for reference, the limit for what we call small molecules is around 1500 da), so there's been a lot of opportunity for tinkering.

FWIW, the full paper is available at https://sci-hub.tw/10.1056/nejmms1411398