After Another Look, Vadadustat (VAFSEO) Becomes the Second HIF-PHD Inhibitor Approved by the FDA
vadadustat (VAFSEO)
oral HIF-PHD enzyme inhibitor Ph. III candidate for anemia in CKD carboxylic acid class of HIF-PHD inhibitors J. Pharmacol. Exp. Ther., Oct 1, 2022 Akebia Therapeutics, Cambridge, MA
Other molecules you may be interested in
atrasentan (ABT-627, A-127722)
Atrasentan, an ETA receptor antagonist discovered by Abbott (AbbVie) in the 1990s, was initially developed for prostate cancer. Due to insufficient clinical data for approval, AbbVie shifted its focus to chronic kidney diseases, conducting a large trial (SONAR) with over 5,000 patients. AbbVie later exited kidney disease drug development and out-licensed atrasentan to Chinook. Novartis then surprised everyone with a $3.2B buyout of Chinook. This case exemplifies the complexities of drug discovery for kidney diseases and the long journey from initial research to clinical success.
"Compound 19" (iron-binder)
“Compound 19” (iron-binder) is an oral inhibitor of the hypoxia-inducible factor (HIF) propyl hydroxylase domain (HIF-PHD), increasing HIF levels to activate EPO transcription and promote hematopoiesis for treatment of anemia. Interestingly, this compound is modeled to make a bi-dentate interaction with an iron co-factor of HIF-PHD via a [...]
sparsentan
An old BMS program revitalized as a first-in-class drug in a new indication. Despite Travere Therapeutics having a checkered industry history due to ties to Martin Shrkeli, there appears to be potentially differentiating efficacy for sparsentan’s ( Filspari ) accelerated approval thanks to its novel dual-antagonistic mechanism. It’s also [...]
inaxaplin (VX-147)
Inaxaplin (VX-147), developed by Vertex, is an inhibitor of APOL1 channel activity currently in a Ph. II/III pivotal study for the treatment of chronic kidney disease caused by specific variants of the APOL1 gene. It was recently granted Breakthrough Therapy designation by the FDA and PRIME designation by the EMA. The discovery story, which is an excellent case study for the use of MetID. Inaxaplin has been called “the most important genomic-driven drug discovery for chronic kidney disease this century”, acting on a target with a fascinating human genetic validation story.
“Compound 9”
“Compound 9” is the first potent M3-selective positive allosteric modulator, with potential utility as a biological tool compound. It does have secondary activity against M5 at high doses though. It’s quite a large zwitterion, which is somewhat unusual for GPCRs.