Biotech Values

[iwfal]

It would be naive to think there were zero LFT abnormalities in ph 2 since placebos have LFT abnormalities.

But they haven't had *any* LFT issues in the placebo arms of the reported Roxa or AKBA NDD HIF RCT trials. Which, combined with the fact that they had explicit issue in the earlier drug, is my point. E.g. there was also a withdrawl from 017 in treated for liver disfunction. An alcoholic, but nonetheless the point stands that we don't have a good placebo base - but the one we have says liver excursions don't happen often in this population.

The rate of LFT abnormalities was more or less in line w placebo

See above. There isn't good published literature (what there is says LFTs are lower than in the general population), but the FGEN data we see says LFTs are rare in this untreated pop, and they had a major problem on the previous drug. FWIW.

that said i do think some idiosyncratic SAE like a liver failure remains a risk to the program (along w some link w CA, etc.)

It wouldn't completely surprise me. But OTOH I think unless it is very common (unlikely) it is unlikely to jeopardize the EPO resistant indications.

on cardiac i tend to think fgen may prove better than epo - although your concern about the temporal nature of events is duly noted

My speculation would agree that on cardiac they are probably better even in comparison to placebo. Normalizing the iron regulation system is likely a powerful good. But just speculation along with my favorite speculation - that it significantly slows GFR decline (as I know you know, HIF actors are potent actors in some kinds of kidney injury).