P1868TO INVESTIGATE THE EFFICACY AND SAFETY OF MOLIDUSTAT IN NON-DIALYSIS PATIENTS WITH RENAL ANEMIA WHO ARE TREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS: MIYABI ND-M

Abstract

Background and Aims: Anemia is a common complication of chronic kidney disease (CKD). A hypoxia‐inducible factor prolyl‐hydroxylase (HF‐PH) inhibitor is developing as a new treatment option of renal anemia. Molidustat, an oral HIF‐PH inhibitor, stimulated endogenous production of erythropoietin and was well tolerated in phase IIb clinical trials. The phase III program entitledMolIdustat once dailY improves renal Anemia By Inducing EPO (MIYABI) was conducted in Japan. Method: MIYABI Non‐Dialysis‐Correction (ND‐C) of Hb study (up to 52 weeks, randomized, darbepoetin‐controlled, open‐label) was conducted to investigate the efficacy and safety of molidustat (MO) in non‐dialysis patients with renal anemia who are not treated with erythropoiesis‐stimulating agents. Study drug doses were titrated regularly with the aim of correcting and maintaining the patients' Hb values between the target range (11.0‐13.0 g/dL). The primary efficacy variables were the mean Hb values during the evaluation period (30‐36 weeks) and its change from baseline to demonstrate the non‐inferiority ofMOto darbepoetin alfa (DA) using a non‐inferiority margin of 1.0g/dL. Safety variables included adverse events (AE). Prespecified primary analysis results up to 36 weeks are presented here. Results: 82 patients were treated with a starting dose of 25mg ofMO and 79 patients were treated with a starting dose of 30lg/2weeks of DA. The mean of baseline Hb values were 9.84 g/dL and 10.00 g/dL in theMOand DA group, respectively.MOincreased the mean Hb values (rate of rise from baseline in Hb values at the first dose change up to 8 weeks: mean: 0.086 g/dL/week (95%CI; 0.047, 0.126)) and achieved the lower limit of target range at 12 weeks.MOmaintained Hb values after 12 weeks, and for the mean Hb values during the evaluation period, the mean was 11.28 g/dL (95%CI; 11.07, 11.50). As the primary efficacy variables (the changes from baseline of mean Hb values during the evaluation period), the means were 1.45 g/dL (95%CI; 1.21, 1.68) and 1.70 g/dL (95%CI; 1.47, 1.92) in theMOand DA group, respectively. The LS mean difference was ‐0.38 (95%CI; ‐0.67, ‐0.08), therefore the non‐inferiority ofMO to DA was established. The mean (SD) doses during the study period were 45.33 (28.88) mg/day ofMOand 17.87 (12.49) lg/week of DA. The most common maximum dose ofMO was 25 mg (26 patients, 31.7%) followed by 75 mg (16 patients, 19.5%) and 50mg (14 patients, 17.1%). AEs were experienced in 84.1% of patients in theMOgroup and in 91.1% of patients in the DA group up to 36 weeks. The most common AEs occurred ≥5% of patients in any group were nasopharyngitis (20.7% and 25.3%, respectively) and worsening of chronic kidney disease (13.4% and 6.3%, respectively). Conclusion: Correction and Maintenance effect ofMOon the Hb values was investigated and the non‐inferiority ofMOto DA was established in non‐dialysis patients with untreated anemia. TheMOshowed no new safety concern but further longitudinal investigation will be needed.