Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients.

Abstract

Safety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb≤10.0 g/dl) patients incident to hemodialysis (HD) or peritoneal dialysis (PD). Sixty patients received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks. Mean±SD baseline Hb was 8.3±1.0 g/dl in enrolled patients. Roxadustat at titrated doses increased mean Hb by ≥2.0 g/dl within 7 weeks regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality. Mean±SEM maximal change in Hb from baseline (ΔHb(max)), the primary endpoint, was 3.1±0.2 g/dl over 12 weeks in efficacy-evaluable patients (n=55). In groups receiving oral or IV iron, ΔHb(max) was similar and larger than in the no-iron group. Hb response (increase in Hb of ≥1.0 g/dl from baseline) was achieved in 96% of efficacy-evaluable patients. Mean serum hepcidin decreased significantly 4 weeks into study: by 80% in HD patients receiving no iron (n=22), 52% in HD and PD patients receiving oral iron (n=21), and 41% in HD patients receiving IV iron (n=9). In summary, roxadustat was well tolerated and corrected anemia in incident HD and PD patients, regardless of baseline iron repletion status or C-reactive protein level and with oral or IV iron supplementation; it also reduced serum hepcidin levels.

• Authors: Anatole Besarab, Elena Chernyavskaya, Igor Motylev, Evgeny Shutov, Lalathaksha M Kumbar, Konstantin Gurevich, Daniel Tak Mao Chan, Robert Leong, Lona Poole, Ming Zhong, Khalil G Saikali, Marietta Franco, Stefan Hemmerich, Kin-Hung Peony Yu, Thomas B Neff
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 27 Issue 4 Pg. 1225-33 (Apr 2016) ISSN: 1533-3450 [Electronic] United States
• PMID: 26494833 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by the American Society of Nephrology.

Chemical References

• Hepcidins
• Isoquinolines
• Glycine
• roxadustat

Topics

• Anemia (blood, drug therapy)
• Female
• Glycine (analogs & derivatives, therapeutic use)
• Hepcidins (blood)
• Humans
• Isoquinolines (therapeutic use)
• Male
• Middle Aged
• Peritoneal Dialysis
• Renal Dialysis