Replies to post #226876 on Biotech Values

[jq1234]

I’ll try to answer your rhetorical question:

It would be much clearer if they release MACE results from both ITT analysis and on-treatment analysis, and results showed there are no dramatic differences for DD including subgroups ID, SD, and NDD between the two different methodologies.

Common replies: AZN/FGEN agreed with FDA on the methodology. Well, 1st this was post hoc agreement, not pre-agreement, there are differences between the two from regulatory point of view. 2nd FGEN PR and filing stated agreement was on primary analysis. Since this was post hoc agreement, the distinction between primary analysis and secondary and sensitivity analysis isn’t as material as most think. FGEN filing made clear about other analyses needed:

The below cardiovascular safety analyses reflect the pooling strategy and analytical approach we agreed on with the FDA. Similar sets of analyses will be submitted to the EMA to serve as the basis for potential approval in dialysis and non-dialysis in Europe, and additional supportive analyses and sensitivity analyses as well as subgroup analyses will also be included in the NDA and MAA. However, the FDA and EMA will each conduct their own benefit-risk analysis and may use additional statistical analyses other than those agreed with the FDA or set forth below, including, but not limited to, pre-specified or other analyses that may not sufficiently address the differential drop-out rate between the roxadustat and placebo study arms in non-dialysis.

o Non-Dialysis - Pooled Cardiovascular Safety Data
In our pre-NDA meeting, the FDA agreed that the ITT-analysis would be our primary cardiovascular safety analysis method for non-dialysis in the U.S. as it uses on-treatment and post treatment long term follow-up (until a common study end date) to account for the higher drop-out rate in the placebo arm.

It is quite clear to me what it says: those who think these “primary analysis” are the only thing matter is just wrong. Question then is how big the differences would be? I don’t know, neither do most except maybe a few insiders, I am not sure those presenters at ASN even saw those analyses. Based on AZN/FGEN behavior - had there ever been any other companies the size of AZN/FGEN who made rollout of major data this confusing? - it tells me differences are significant, but until you see those analyses you can’t make more definitive conclusion one way or the other.

Many are trashing the short report, to be honest it made many similar points I made including but not limited to differences in dropouts between roxadustat and epo in DD. At minimum it showed same data could be analyzed so many different ways which raises the question why don’t they just release more straightforward data as I suggested? Additionally Pyrenees study - no one else picked up on this previously - is important because it was the only dedicated SD study while other DD studies are either in ID or mixed ID and SD. They still haven’t released MACE in their pooled SD subgroup yet, I’d be really curious what would pooled SD results including Pyrenees look like because I am quite sure they have adjudicated MACE for Pyrenees and it would be easy to have that analysis done.

https://twitter.com/jq1234t/status/1192901288264114178?s=21

https://twitter.com/jq1234t/status/1194334883822391296?s=21

[zipjet]

The Bloomberg screen shot is what I saw.

jb is right about the language which I did not handle as carefully as jb.