Safety concerns with erythropoietin analogues and intravenous ( IV ) iron for treatment of anemia in chronic kidney disease ( 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.
Researchers performed an open-label, randomized hemoglobin ( Hb ) correction study in anemic ( Hb less than or equal to 10.0 g/dl ) patients incident to hemodialysis or peritoneal dialysis.
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 greater than or equal to 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 ( ΔHbmax ), 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, ΔHbmax was similar and larger than in the no-iron group.
Hb response ( increase in Hb of greater than or equal to 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 hemodialysis patients receiving no iron ( n=22 ), 52% in hemodialysis and peritoneal dialysis patients receiving oral iron (n=21), and 41% in hemodialysis patients receiving IV iron (n=9).
In conclusion, Roxadustat was well tolerated and corrected anemia in incident hemodialysis and peritoneal dialysis 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. ( Xagena )
Besarab A et al, J Am Soc Nephrol 2015; Epub ahead of print