Highlights
The problem is that there were people thinking [cardiovascular events] were inherent with the ESAs, or is it because of too much change in biology, in the viscosity of the blood as you increase hemoglobin from 8 to 11, 12, or even 13, or if it’s something about ESA itself that is causing this. So, there were a lot of debates, a lot of discussions, then there was a huge study by Amgen, the study was called TREAT, which was one of the largest ESRD/CKD studies that looked at events in these types of patients, 4,000 patients, for more than four years, and it showed that ESAs can be given in a safe manner as long as the hemoglobin does not go above 10.5.
So, coming back to HIFs, it has several good responses, number one a physiological rise in erythropoietin, number two a reduction of hepcidin, number three liberating iron. So, you have a perfect nice niche that you allow ineffective erythropoietin to become effective, and the patients can respond, and do well.
There’s a big problem there that I think has not been resolved, and that’s why I am negative on HIFs. I gave you all the positives, but I’ll mention a few of the negatives. Number one, we know that HIFs stimulate VEGF, VEGF causes vascular proliferation, HIFs are very important in cancer, why? As the cancer cell grows very rapidly the blood supply is limited, so you can get into hypoxia, hypoxia causes HIF to be activated and angiogenesis is produced, so you have more vessels going into a newly formed and rapidly growing cancer cell. So, imagine you’re giving HIFs, and it can activate VEGF, you have so many diabetic nephropathies, with retinopathy of the eyes that can be affected, there are so many patients that could be having a nidus of cancer, and this can make it grow rampant, and become very dangerous.
We know that more than 200 genes are activated [with HIFs stabilizers], some of them good, some of them we don’t know, some of them are detrimental, are you willing to take this drug versus a safe drug that has been around for more than 25 years, and we know how to give it, and we have learned how to avoid MACE and other issues… I’m very, very disturbed by all these gene activations that no one is paying attention to.
This interview with a US-based key opinion leader (KOL) provides insights into prescribing habits, key marketed brands, and late-phase pipeline therapies for anemia in chronic kidney disease (CKD). Key topics discussed include current treatments for anemia in CKD, with a focus on ESAs and IV iron, and the future of HIF stabilizers as a potential treatment for the disease.