summary of Feedback received from a UK-based nephrology expert,...

summary of Feedback received from a UK-based nephrology expert, for those SH interested in the science:

# FDA and EMA do not accept the surrogate of proteinuria reduction in fsgS for accelerated or conditional approval because there is currently no data to support a quantitative association between proteinuria and GFR in fsgs. Contrast this with IGA nephropathy where meta-analysis has conclusively shown this asscotiation which is why tarpeyo (calliditas) and sparsentan (travere) got conditional approval in IGA nephropathy based on proteinuria.
# DUPLEX sparsentan study possibly tripped up partly because of how heteregeneous FSGs is and other factors such as extent of fibrosis in kidneys. The DMX trial will probably have to deal with these same challenges that could affect efficacy, independent of how the drug works. Many in the nephrology community to do not consider fsg to be a defined disease or specific diagnosis, rather it's biopsy lesion finding. For a good review on this read the review article in nephrology dialysis transplantation journal by Zand ('what are we missing in the clinical trials of fsgs?") 2017, 32: i14-i21
# chemokine inhibiition including targeting ccr2 has not been successful in chronic kidney diseases, there is evidence for tolerance to these drugs that reduces efficacy over time and the long tern safety of chronic chemokine inhibition which affect immune system is unknown which could also be a concern for a regulator.