Biotech Values

[iwfal]

FGEN - Links to relevant papers and some key liver quotes:

Trial 017 (NDD):

https://www.researchgate.net/profile/Anatole_Besarab2/publication/285420191_Besarab_2015_NDT_Study_017_NDD_roxadustat/links/565e24d408ae4988a7bd3d0c.pdf

Key quotes:

Liver function was monitored. One patient with a history of
heavy alcohol intake had study treatment discontinued due to
elevated alanine aminotransferase (ALT), aspartate aminotransferase
(AST) and bilirubin levels following the first dose of study drug, all of which normalized within a week. No evidence of liver toxicity or sustained increases of liver enzymes or serum bilirubin were reported in this study.

Note the interesting fact that the last sentence doesn't really gibe with the earlier paragraphs. And note that AE table doesn't include the LFT excursions.


Trial 053 (Incident Dialysis):

https://www.researchgate.net/profile/Anatole_Besarab2/publication/283210436_Roxadustat_FG-4592_Correction_of_Anemia_in_Incident_Dialysis_Patients/links/565e1f5a08aeafc2aac8d6d5.pdf

Key quote:

One patient in the IV iron cohort had an alanine aminotransferase
level 3.3 times the upper limit of normal at predose on day of randomization; this became normal in a few days and remained normal while treatment with roxadustat resumed and continued for the rest of
treatment period.

The text is not entirely clear, but:

a) the key word is "resumed".

b) And the key to understanding this is that the protocol diagram in the paper implies they started Roxa and then split into the various iron groups. I.e. randomization probably happened after start of Roxa.

And, finally, the link to 041 (NDD again):

http://cjasn.asnjournals.org/content/early/2016/05/01/CJN.06890615.full


And my comments:

1) there is an apparent pattern of obfuscation (e.g. not in the table numbers, only in the text in multiple papers) on liver issues (the great thing about putting this stuff out there is it makes me put the pieces together in different ways)

2) all the significant issues crop up very early in the trial (e.g. both of the above events were very early, and, as I noted in my post yesterday, the CV issues also appear very early.) It looks like a giant bodywide remodelling.

3) 041, which I suspect was a later trial (e.g. last published), explicitly excludes anyone who has more than 3 drinks a day. 041 also avoided the withdrawls for liver issues.