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 *
22 October 2015
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.