Biotech Values

[iwfal]

FGEN -

I'm on mobile so will be brief. In general I think there's every reason to pay attention to liver se. Not only in light of prior hold for first fgen agent but also the moa which probably relies on liver for epo production. The randomized trial of one case of lft excursion in a drinker really doesn't bug me. The fact there were no liver elevation among 29 placebo pts in the study that you pointed out in prior email also doesn't bother me. Fact is there was no drug related liver tox in the study by any reasonable measure. The second case is off putting it clearly happened after Roca dosing and one shouldn't have to work to figure this out. I expect better from this management team. That said I think liver tox is a relatively low risk for the program at this juncture but it's still a risk (and will be even in early stages of launch if its a one in ten thousand deal).

Although I mostly agree with you (e.g. I consider the lack of forthrightness as big a concern as the potential liver tox - or bigger (as I alluded to in the original post)), but some potential, minor, disagreements:

While I agree that the mapping of ALT >3xULN to Hy's Law is poorly understood, I think the other things make it a bigger risk than they would if the only thing we saw was the 2.8% ALT >3xULN. The bilirubin, the spike in ALT on first dose, and even the quick liver tox in the alcoholic. Further there is data that Fibrogen hasn't actually published, so far as I can tell: they appear to have run a special trial just to determine how the drug worked in those with moderate liver impairment ( https://clinicaltrials.gov/ct2/show/NCT02161224?term=roxadustat&rank=11&submit_fld_opt= ). Perhaps nothing of importance happened, but given their behavior it is reasonable, IMO, to wonder.

BTW - I'll reiterate what I have said before (on the subject of IONS): all companies have character flaws - e.g. hiding safety data is a big one, and another is massive post hocing - so, by itself it can't be a disqualifier. But it does go into the decision mix for me.

BTW2 - Interesting note: the only company for which I have never been able to find a systemic flaw has been BMRN. It actually kinda bugs me -g-.