Molidustat appears noninferior to darbepoetin alfa in correcting hemoglobin (Hb) in nondialysis chronic kidney disease (CKD) patients not previously treated with an erythropoiesis-stimulating agent (ESA) and in maintaining Hb in patients who have been treated with ESAs, according to the results of 2 late-breaking trials presented at the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 2020 virtual congress.
Molidustat is an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI) that stimulates the endogenous, predominantly renal, production of erythropoietin.
In the MIYABI (MolIdustat once dailY improves renal Anemia By Inducing EPO) Non-Dialysis-Correction phase 3 trial, 82 Japanese patients with baseline Hb of 9.84 g/dL were treated with molidustat (starting dose 25 mg) and 79 patients with Hb 10.00 g/dL were treated with darbepoetin (starting dose 30 μg/2 wks). By 12 weeks, molidustat had increased mean Hb to the lower limit of the 11.0 to 13.0 g/dL target range and then maintained it at a mean 11.28 g/dL during weeks 30 to 36. The mean change in Hb from baseline was 1.45 g/dL in the molidustat group and 1.70 g/dL in the darbepoetin group, according to the investigators. The least square mean difference of -0.38 demonstrated noninferiority, Hiroyasu Yamamoto, MD, PhD, of the Jikei University School of Medicine in Tokyo, and colleagues reported.
During the study, mean doses were 45.33 mg/d for molidustat and 17.87 μg/wk for darbepoetin. Nearly a third of the molidustat group had a maximum dose of 25 mg, 17% reached 50 mg, and a fifth reached 75 mg.
In the MIYABI Non-Dialysis Maintenance phase 3 trial, the same research team assigned 82 patients to molidustat (starting dose 25 or 50 mg) and 82 patients to darbepoetin (with starting doses in accordance with previous ESA dose and interval). Molidustat maintained Hb at a mean 11.67 g/dL from a baseline value of 11.31 g/dL, with 80.5% of patients staying within target range. During weeks 30 to 36, the mean change in Hb from baseline was 0.35 g/dL and 0.26 g/dL in the molidustat and darbepoetin group, respectively. A least square mean difference of 0.13 established the noninferiority of molidustat, Dr Yamamoto’s team reported.
Mean doses were 52.16 mg/d for the molidustat group and 21.33 μg/wk for the darbepoetin group.
With respect to adverse events, no new safety concerns emerged in the 2 trials. Most patients in both trials experienced an event: 84.1% vs 91.1% of molidustat and darbepoetin patients in the correction trial and 87.8% vs 89.0%, respectively, in the maintenance trial. Less than a third of patients in both trials developed nasopharyngitis. More molidustat than darbepoetin patients experienced worsening of CKD: 13.4% vs 6.3%, respectively, in the correction trial and 12.2% vs 7.3%, respectively, in the maintenance trial.
Please see the original references for a full list of authors’ disclosures.
Yamamoto H, Taguchi M, Nobori K, et al. To investigate the efficacy and safety of molidustat in nondialysis patients with renal anemia who are not treated with erythropoiesis-stimulating agents: MIYABI ND-C. Nephrol Dial Transplant. Presented at the European Renal Association-European Dialysis and Transplant Association 2020 virtual congress. Abstract P1866.
Yamamoto H, Taguchi M, Nobori K, et al. To investigate the efficacy and safety of molidustat in nondialysis patients with renal anemia who are treated with erythropoiesis-stimulating agents: MIYABI ND-M. Nephrol Dial Transplant. Presented at the European Renal Association-European Dialysis and Transplant Association 2020 virtual congress. Abstract P1868.