SP334IRON REGULATION BY MOLIDUSTAT, BAY 85-3934, A DAILY ORAL HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITOR IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract

INTRODUCTION AND AIMS: Dysregulation of iron metabolism occurs frequently in patients with chronic kidney disease (CKD) and contributes to development of anemia. Accumulating evidence has shown that hypoxia‐inducible factor (HIF) is an important regulator of iron metabolism under hypoxic conditions. Therefore, we studied whether molidustat, a HIF‐prolyl hydroxylase (PH) inhibitor, by stabilizing HIF activity, has an effect on iron metabolism in patients with CKD. METHODS: A Phase 2b study (up to 16 weeks, randomized, placebo‐controlled, openlabel, fixed‐dose) was conducted in anemic ESA‐treatment‐naïve subjects with CKD who were not in dialysis who had ferritin levels≥100 lg/L and<1,000 lg/L or transferrin saturation (TSAT)≥ 20% at screening. Serum ferritin, iron, total iron binding (TIBC), TSAT and hepcidin were measured to assess iron metabolism. Iron supplementation was administered at the discretion of the physician with the goal of maintaining adequate levels during the study. RESULTS: 35 subjects (34.7 %) of the 101 subjects treated with molidustat and 8 subjects (40.0 %) of the 20 subjects treated with placebo received iron supplementation prior to the study. Iron supplementation was started in 10.9% of subjects on molidustat and in 25.0% of subjects on placebo. Iron supplementation was discontinued in 4.0% of subjects on molidustat and 25.0% of subjects on placebo. During the study period, molidustat corrected hemoglobin (Hb) values and decreases from baseline to 16 weeks in ferritin, iron, TSAT and hepcidin values were observed in the molidustat group, along with an increase in TIBC. In contrast, Hb values and iron parameters remained near baseline levels in the placebo group (Table 1). CONCLUSIONS: Molidustat appears to have an effect on iron metabolism, as manifest by changes in iron parameters, while at the same time correcting hemoglobin values in patients with CKD (Table presented).