A Phase 3 Study of Enarodustat in Anemic Patients with CKD not Requiring Dialysis, the SYMPHONY ND Study

Abstract 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 (non-inferiority to darbepoetin alfa [DA]) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis. Methods Erythropoiesis-stimulating agent (ESA)-naive 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 (10–12 g/dL). The primary endpoint was the difference in the mean Hb level between arms during the evaluation period defined as Weeks 20–24 (non-inferiority 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, 11.07) with a difference of 0.09 g/dL (95% CI: −0.07, 0.26) between arms, establishing its non-inferiority 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]). Conclusion 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.