BACKGROUND: Daprodustat is an oral agent that stimulates erythropoiesis by 
inhibiting the prolyl hydroxylases which mark hypoxia-inducible factor for 
degradation through hydroxylation. Its safety and efficacy (noninferiority) were 
assessed in this 52-week, open-label study.
METHODS: Japanese patients not on dialysis (ND) (N = 299) with anemia of CKD 
(stages G3, G4, and G5) with iron parameters of ferritin >100 ng/mL or 
transferrin saturation >20% at screening were randomized to daprodustat or 
epoetin beta pegol (continuous erythropoietin receptor activator [CERA], also 
known as methoxy polyethylene glycol-epoetin beta). After initiation of the 
study, the daprodustat starting dose for erythropoiesis-stimulating agent 
(ESA)-naïve participants was revised, and daprodustat was started at 2 or 4 mg 
once daily depending on baseline hemoglobin. ESA users switched to daprodustat 4 
mg once daily. CERA was started at 25 μg every 2 weeks for ESA-naïve patients 
and 25-250 μg every 4 weeks for ESA users based on previous ESA dose. In both 
treatment groups, dose was adjusted every 4 weeks based on hemoglobin level and 
changed according to a prespecified algorithm. The primary endpoint was mean 
hemoglobin level during weeks 40-52 in the intention-to-treat (ITT) population. 
ESA-naïve patients who entered before the protocol amendment revising the 
daprodustat starting dose were excluded from the ITT population.
RESULTS: Mean hemoglobin levels during weeks 40-52 were 12.0 g/dL in the 
daprodustat group (n = 108; 95% confidence interval [CI], 11.8-12.1) and 11.9 
g/dL for CERA (n = 109; 95% CI 11.7-12.0); the difference between the groups was 
0.1 g/dL (95% CI -0.1 to 0.3 g/dL). The lower limit of the 95% CI of the 
difference was greater than the prespecified margin of -1.0 g/dL. The mean 
hemoglobin level was within the target range (11.0-13.0 g/dL) during weeks 40-52 
for 92% of participants in both groups. There was no meaningful difference in 
the frequencies of adverse events.
CONCLUSIONS: Oral daprodustat was noninferior to CERA in achieving and 
maintaining target hemoglobin levels in Japanese ND patients. Daprodustat was 
well tolerated, with no new safety concerns identified.