A newly disclosed sGC activator in Ph. II for CKD/DKD. This month, researchers at BI reported promising preclinical results for a newly disclosed sGC activator, BI-685509, which is in several Ph. II trials including for treatment of chronic kidney disease (CKD) and diabetic kidney disease (DKD) ( NCT04736628 , NCT04750577 ). In rodents, the [...]

“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.

Daprodustat is the first HIF-prolyl hydroxylase domain (PHD) inhibitor that has been approved for the treatment of anemia in chronic kidney disease (CKD) and marks the first novel anemia treatment approved in the US in >30 years. PHDs have been attractive targets for treating anemia, especially in CKD patients, because the enzymes regulate levels of hypoxia-inducible factors (HIFs) including HIF-2, which induces the production of erythropoietin that in turn stimulates red blood cell production. The small molecule drug has similar safety and activity as epoetin alfa, an injected biologic.

Vadadustat (Vafseo) from Akebia Therapeutics is an oral hypoxia-inducible factor prolyl-4-hydroxylase domain (HIF-PHD) inhibitor developed for anemia in patients with chronic kidney disease (CKD). It received FDA approval on March 27th, 2024 for patients on dialysis for at least three months, after regulatory challenges including an earlier complete response letter due to safety concerns. This makes vadadustat the second FDA-approved HIF-PHD inhibitor for the treatment of anemia in CKD for dialysis-dependent patients after GSK’s daprodustat’s approval in Feb. 2023.

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 [...]