Roxadustat Improved Iron Homeostasis in Patients with NDD-CKD

Kidney Week 2020

The causes of anemia in patients with chronic kidney disease are multifactorial, including reductions in production of erythropoietin and hepcidin-induced functional iron deficiency. Roxadustat treats anemia by enhancing erythropoietin synthesis and increasing iron availability via reduction in hepcidin and increase in iron transport. Steven Fishbane, MD, and colleagues conducted an analysis to examine the effect of roxadustat on iron parameters in patients with non–dialysis-dependent (NDD) CKD.

In three pivotal double-blind trials of roxadustat in patients with NDD-CKD, trial participants were randomized to receive roxadustat or placebo. Oral iron was administered without restriction per the discretion of the treating physician, and use of intravenous (IV) iron was limited to rescue therapy. The outcomes of interest were mean changes from baseline in hemoglobin (Hb), hepcidin, and iron parameters.

The researchers reported pooled results from the three studies during a virtual poster session at ASN Kidney Week 2020. The poster was titled Hemoglobin (Hb) Correction with Roxadustat Is Associated with Improved Iron Homeostasis in Patients with Non–Dialysis-Dependent CKD (NDD-CKD).

A total of 4277 patients were evaluated, 2391 in the roxadustat arm and 1886 in the placebo arm. In both groups, mean estimated glomerular filtration rate was 20 mL/min/1.73 m², and baseline Hb was 9.1 g/dL. Roxadustat was superior to placebo in increasing mean Hb from baseline averaged over weeks 28 to 52 (1.9 vs 0.2 g/dL, respectively; P<.0001). During the first 52 weeks, 2.1% of patients in the roxadustat arm required IV iron use compared with 4.8% of those in the placebo arm.

Roxadustat reduced hepcidin and increased transferrin and serum iron. Reductions in ferritin and transferrin saturation were seen predominantly in patients with the highest baseline values of those parameters when assessed by quartile (>328 µg/L and >35%, respectively).

In summary, the researchers said, “Roxadustat increased both serum iron and iron-carrying capacity (transferrin) while simultaneously inducing erythropoiesis and correcting anemia in patients with NDD-CKD, without the need for regular IV iron supplementation.”

Source: Fishbane S, Charytan C, Little DJ, Tham S, Leong R, Pergola PE. Hemoglobin (Hb) correction with roxadustat is associated with improved iron homeostasis in patients with non–dialysis-dependent CKD (NDD-CKD). Abstract of a poster presented at the American Society of Nephrology virtual Kidney Week 2020 (Abstract PO0257), October 22, 2020. Funding for this poster was provided by AstraZeneca.