A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study
Chaim Charytan, Roberto Manllo-Karim, Edouard Martin, Dylan Steer, Marializa Bernardo, Sohan Dua, Moustafa A. Moustafa, Gopal Saha, Charles W. Bradley, Meraf Eyassu, Robert Leong, Khalil G. Saikali, Cameron Liu, Lynda A. Szczech, Kin-Hung P. Yu
Abstract
INTRODUCTION: Erythropoiesis-stimulating agents, standard of care for anemia of end-stage kidney disease, are associated with cardiovascular events. We evaluated the efficacy and safety of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. METHODS: SIERRAS was a phase 3, randomized, open-label, active-controlled study enrolled adults on dialysis for end-stage kidney disease receiving erythropoiesis-stimulating agents for anemia. Patients were randomized (1:1) to thrice-weekly roxadustat or epoetin alfa. Doses were based on previous epoetin alfa dose and adjusted in the roxadustat arm to maintain hemoglobin at ∼11 g/dl during treatment. Epoetin alfa dosing was adjusted per US package insert. Primary efficacy endpoint was mean hemoglobin (g/dl) change from baseline averaged over weeks 28 to 52. Treatment-emergent adverse events were monitored. RESULTS: 001) to epoetin alfa. Tolerability was comparable between treatments. CONCLUSION: In end-stage kidney disease, roxadustat was noninferior to epoetin alfa in up to 52 weeks of treatment in this erythropoietin-stimulating agent conversion study. Roxadustat had an acceptable tolerability profile.