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766 Hemoglobin (Hb) Correction with Roxadustat Is Associated with Improved Iron Homeostasis in Patients with Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD)

Program: Oral and Poster Abstracts
Session: 102. Regulation of Iron Metabolism: Poster I
Hematology Disease Topics & Pathways:
Anemias, Adult, Non-Biological, Diseases, Therapies, Biological Processes, Study Population, Clinically relevant, iron metabolism, iron transport
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Steven Fishbane1*, Chaim Charytan2*, Dustin Little3*, Stefan Tham4*, Robert Leong5* and Pablo E Pergola6*

1Department of Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY
2New York Hospital Queens, Division of Nephrology, Flushing, NY
3Clinical Research, AstraZeneca, Gaithersburg, MD
4Clinical Research, AstraZeneca, Gothenburg, Sweden
5FibroGen Inc., San Francisco
6Renal Associates PA, San Antonio, TX

Background: Anemia in CKD is multifactorial, with contributions from reduced erythropoietin production and hepcidin-induced functional iron deficiency. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, treats anemia by enhancing erythropoietin synthesis and increasing iron availability via reducing hepcidin and increasing iron transport. We assessed the effect of roxadustat on iron parameters in patients with NDD-CKD.

Methods: Patients were randomized to double-blind roxadustat or placebo in 3 pivotal NDD-CKD trials. Oral iron was administered without restriction per discretion of the treating physician, and intravenous (IV) iron use was limited to rescue therapy. Mean changes from baseline (BL) in Hb, hepcidin, and iron parameters were evaluated. Pooled results are reported.

Results: Overall, 4277 patients were evaluated (roxadustat N=2391; placebo N=1886). Mean estimated glomerular filtration rate (eGFR) was 20 ml/min/1.73 m2 in both groups. Roxadustat was superior to placebo in increasing mean Hb from BL (9.1 g/dL for both groups) averaged over Weeks 28–52: 1.9 vs 0.2 g/dL (P<0.0001). IV iron use was required in 2.1% of roxadustat vs 4.8% of placebo patients during the first 52 weeks after randomization. Roxadustat reduced hepcidin and increased both transferrin and serum iron (Figure). Reductions in ferritin and transferrin saturation occurred predominantly in patients with the highest BL values of these parameters when assessed by quartile (>328 µg/L and >35%, respectively).

Conclusion: 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.

Disclosures: Fishbane: Akebia Inc.: Research Funding; Ardelyx: Research Funding; AstraZeneca: Consultancy, Research Funding; MegaPro Biomedical Co Ltd: Research Funding; Cara Therapeutics: Research Funding; Corvidia Therapeutics: Research Funding. Charytan: Akebia: Research Funding; GSK: Research Funding; Fibrogen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding. Little: AstraZeneca: Current Employment, Current equity holder in private company. Tham: AstraZeneca: Current Employment, Current equity holder in private company. Leong: FibroGen Inc.: Current Employment, Current equity holder in private company. Pergola: AstraZeneca: Consultancy, Research Funding.

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