VIDEO: Exciting approvals, treatments in the pipeline for anemia management in CKD

Editor’s note: This is a previously posted video, and the below is an automatically generated transcript to be used for informational purposes. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

There are several newer classes of agents that are in the drug development pipeline which may have a significant impact on changing our approach to anemia in patients with chronic kidney disease. The most notable of which is the hypoxy inducible factor, or HIF, prolyl hydroxylase inhibitor, PHI, class of drugs. I'll talk about them about them as HIF stabilizers, because their actual mechanism of action is to prevent the degradation of HIF, and potentiate its activity, which ultimately leads to the transcription of a number of genes that are related to erythropoiesis, including not only erythropoietin and the erythropoietin receptor, but a number of iron-handling proteins that improve duodenal iron absorption and also improve the release of iron from internal stores in the reticuloendothelial system. So unlike exogenous erythropoietin, which has its own risks that I've alluded to in the previous answers, this new class of agents leads to an endogenous production of erythropoietin at much more physiologic, rather than pharmacologic levels. And it is hoped that this will lead to a decrease in some of those adverse cardiovascular endpoints that have been observed in patients receiving large doses of exogenous erythropoietin-stimulating agents.

Now, getting back to the mechanism of action of this new class of drugs, another attraction is that they are small molecules, and as a result can be administered orally. So this to me is extremely exciting for patients with non-dialysis-dependent chronic kidney disease, who as we mentioned, have to take ESAs perennially. If you have an oral-administered agent, the patient doesn't have to self-administer or go to some healthcare facility to get an injection. They can just take a pill daily or three times a week, whichever happens to be the pharmacokinetics of that particular drug. So that's probably gonna lead to much better compliance and also a bit better mobilization as we said, of iron and absorption of iron. So you won't necessarily see the kinds of iron deficiency states with this newer class of drugs that you generally see with ESAs that really have no mechanism for improving either iron absorption or iron mobilization. So that to me is the most exciting class of drugs.

Now, there are a number of other contenders, shall we say, that address specifically the inflammatory state of chronic kidney disease, which leads to high hepcidin levels. Now high hepcidin is the master regulator of iron metabolism and distribution. And patients with chronic kidney disease, because it is an inflammatory state, tend to have high hepcidin levels, which are compounded by the fact that hepcidin is a small peptide that is degraded by the kidney. So in the presence of renal insufficiency, you have not only increased production, but decreased metabolism. And this leads to very high levels, which pretty much paralyze iron distribution within the body. So you have less iron absorption, you have less iron release from internal stores, less iron delivery to the marrow, and a state of functional iron deficiency. There are variety of products in the pipeline that are specifically targeting these high hepcidin levels through a variety of mechanisms, including monoclonal antibodies, inhibitors of various transcriptional elements that it is hoped that some point may fix this issue which is almost universal in patients with chronic kidney disease. And that's this inflammatory state that leads to functional iron deficiency.