Daprodustat May Reduce Fatigue, Improve Quality-of-life, for Patients with Chronic Kidney Disease

Kirsten Johansen, MD, Director of Nephrology, Hennepin Healthcare, joins Pharmacy Times to discuss daprodustat, which treats anemia caused by chronic kidney disease. Johansen talks about the primary results of past and current trials, which she presented at ASN Kidney Week in Orlando Florida, and a surprising benefit of this medication that even she did not foresee.

Q: Can you review the mechanism of action of daprodustat and what effect is being investigated regarding hemoglobin stability and quality of life in individuals with CKD?

Kirsten Johansen, MD: So daprodustat acts on the hypoxy-induceable factor pathway. Normally, if those factors are produced all the time but if we have enough oxygen around there are enzymes called prolyl hydroxylases that break those down. And daprodustat is a prolyl hydroxylase inhibitor so it inhibits those enzymes and then stabilizes those compounds So that even if you’re hypoxic you still produce and maintain the stability of that compound which then leads to erythropoietin production.

Q: Can you speak on the efficacy (ASCEND-D and -ND) and quality of life (ASCEND-NHQ) findings presented at Kidney Week 2022?

Kirsten Johansen, MD: So a little bit of background, because a lot of the primary results were presented last year. The top line results were presented last year at kidney week. ASCEND D and ND, those were large global cardiovascular trials. They looked at efficacy comparing hemoglobin, to (erythropoiesis-stimulating agents [ESAs]) in Dialysis (D) to non-dialysis (ND). And then also looked at major adverse cardiac events. What they found was that in both D and ND, daprodustat was non-inferior to ESAs in terms of achieved hemoglobin as a primary outcome measure, and then efficacy as an outcome measure- and equivalent in terms of major adverse cardiovascular events.

The other study that we presented results on was the Ascend- NHQ study. This one was not a cardiovascular study; it was a placebo-controlled trial to look at efficacy and then to look at quality of life. and that was in the patient’s not on dialysis. Efficacy was a primary outcome still, and it was effective compared to placebo, with a rise in hemoglobin of about, I think it was about 1.4 g/dL in the group that got daprodustat compared to the placebo group. And then a secondary outcome was fatigue by the vitality score, the SF-36, which asks patients about their level of fatigue.

It was more than a 5-point increase in scale in the people who got daprodustat compared to the group who got the placebo. This year we presented additional quality of life data. They used the vitality score because it’s well known, it’s used in A lot of different trials and a lot of different patient populations. But it’s not to see specific, it’s not specific for people with kidney disease or anemia. So, folks at GSK worked with people from the FDA to determine what they need to do to develop a Measure for this population. And they did that. So, they interviewed patients about their anemia and about their symptoms and we worked together to produce an instrument that would take what they thought were the key symptoms and put it into a questionnaire. Then we went back to them to see if that reflected what they thought. And so, we presented those results here at the 2022 meeting. In those results in terms of fatigue, fatigue was a big part, was one of the scales that came out of the CDKAQ but with a few more questions than what was in the other. they really mirrored. It was a big difference in fatigue, a big reduction and the people who got daprodustat compared to the placebo. But there were also two other skills that came out of that. One was shortness of breath and chest pain, the other was cognitive function. And both of those also improved. And I was not surprised about the shortness of breath and chest pain, but I was surprised by the reduction in cognitive dysfunction that patients reported.

Q: What is important to understand about the quality-of-life benefits of daprodustat?

Kirsten Johansen, MD: Fatigue is one of the most important and most common symptoms that patients with kidney disease face. because that’s the case, anything that improves fatigue is something that I think patients are really excited about, because they suffer a lot from fatigue.