Doc,
Endothelin-receptor antagonists have been trialled previously in nephropathy. Avosentan (http://www.ncbi.nlm.nih.gov/pubmed/20167702) showed good results; but the trial was prematurely terminated because of an excess of cardiovascular events. Others have also been trialled. Given Sparsentan has dual endothelin receptor and angiotensin II receptor antagonism, it intuitively makes sense to give it a go. They do not have a platform tech like Receptor-HIT like DMX. They in-licensed the drig from Ligand pharmaceuticals for FSGS in 2012, who in turn in-licensed it from pharmacopeia/BMS.
I also want to reiterate that we do not need to decrease proteinuria by 50% in patients already on irbesartan to have a valuable drug. The 50%+ reduction seen in the rat model was a combination of Irb/PPG in a naive rat and not 50% reduction in rats already on irbesartan like this human study. So we all need to be clear about what can and should be achieved in terms of proteinuria reduction.
Cheers
A.
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