Molidustat as good as Darbepoetin to correct anemia in CKD patients: Study
Japan: Molidustat (MO) is noninferior to darbepoetin alfa (DA) for the correction of hemoglobin (Hb) in nondialysis chronic kidney disease (CKD) patients with untreated anemia, according to a recent study in the Nephrology Dialysis Transplantation. Further, MO showed no new safety concerns.
The findings were also presented at the European Renal Association-European Dialysis and Transplant Association 2020 virtual congress.
Anemia is a common complication among CKD patients. A hypoxia-inducible factor prolyl-hydroxylase (HF-PH) inhibitor is being developed as a new treatment option of renal anemia. Molidustat is an oral HIF-PH inhibitor that stimulates the production of erythropoietin. It was well-tolerated in phase IIb clinical trials. The phase III program entitled MolIdustat once dailY improves renal Anemia By Inducing EPO (MIYABI) was conducted in Japan.
Hiroyasu Yamamoto, The Jikei University School of Medicine, Tokyo, Japan, and colleagues investigated the efficacy and safety of molidustat in non-dialysis patients with renal anemia who are not treated with erythropoiesis-stimulating agents in this MIYABI Non-Dialysis-Correction (ND-C) of Hb study -- randomized, darbepoetin-controlled, open-label conducted up to 52 weeks. 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). 82 patients were treated with a starting dose of 25mg of MO and 79 patients were treated with a starting dose of 30μg/2weeks of DA.
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 of MO to 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 in this study.
Key findings of the study include:
- The mean of baseline Hb values were 9.84 g/dL and 10.00 g/dL in the MO and DA group, respectively.
- MO increased 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 ) and achieved the lower limit of target range at 12 weeks.
- MO maintained Hb values after 12 weeks, and for the mean Hb values during the evaluation period, the mean was 11.28 g/dL.
- As the primary efficacy variables (the changes from baseline of mean Hb values during the evaluation period), the means were 1.45 g/dL and 1.70 g/dL in the MO and DA group, respectively.
- The LS mean difference was -0.38, therefore the non-inferiority of MO to DA was established.
- The mean (SD) doses during the study period were 45.33 (28.88) mg/day of MO and 17.87 (12.49) μg/week of DA.
- The most common maximum dose of MO 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 the MO group 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).
"The non-inferiority of MO to DA was established in non-dialysis patients with untreated anemia. The MO showed no new safety concern but further longitudinal investigation will be needed," concluded the authors.
The study, "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," is published in the journal Nephrology Dialysis Transplantation.