Introduction: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that might be a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy (noninferiority to darbepoetin alfa [DA]) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis. Methods: Erythropoiesis-stimulating agent (ESA)–naïve patients and ESA-treated patients were randomized at a 1:1 ratio to receive enarodustat orally once daily or DA subcutaneously every 2 or 4 weeks for 24 weeks, respectively. Subjects in each arm had dose adjustments every 4 weeks to maintain their hemoglobin (Hb) level within the target range (10 to 12 g/dl). The primary endpoint was the difference in the mean Hb level between arms during the evaluation period defined as weeks 20 to 24 (noninferiority margin: –0.75 g/dl). Results: The mean Hb level during the evaluation period in the enarodustat arm was 10.96 g/dl (95% confidence interval [CI]: 10.84 to 11.07 g/dl) with a difference of 0.09 g/dl (95% CI: −0.07 to 0.26 g/dl) between arms, establishing its noninferiority to DA. Nearly 90% of subjects in both arms maintained a mean Hb level within the target range. Compared with DA, enarodustat was associated with decreased hepcidin and ferritin, and increased total iron-binding capacity. There were no apparent differences in the incidence of adverse events between arms (65.4% [enarodustat], 82.6% [DA]). Conclusions: The efficacy of enarodustat was comparable to DA in anemic patients with CKD not requiring dialysis. No new safety concerns were identified compared with DA.
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