P0862DAPRODUSTAT INTERACTION WITH PHOSPHATE BINDERS HAS MINIMAL IMPACT ON HEMOGLOBIN VALUES IN HEMODIALYSIS POPULATION

Abstract

Abstract Background and Aims Daprodustat is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) currently in phase 3 development for the treatment of anemia of chronic kidney disease (CKD). Phosphate binders (PB) are widely prescribed for hemodialysis (HD) patients to control for hyperphosphatemia. The coadministration of PB and HIF-PHI may potentially impact hemoglobin values thus requiring time between PB administration and HIF-PHI. The purpose of this analysis was to determine whether daprodustat interaction with PB has an impact on hemoglobin (Hgb) values in the HD population. Method GSK PHI113633 study (NCT01977482) included 216 subjects on maintenance HD previously treated with rhEPO. This study included daprodustat dose-ranging for the first 4 weeks, followed by a Hgb correction/maintenance phase for the next 20 weeks; daprodustat was dosed daily without regard to the timing of PB administration. The control group received placebo for 4 weeks, followed by rhEPO for the next 20 weeks as previously reported (Clin Kidney J 2019;12(1):139-148). Target Hgb range was 10.0-11.5 g/dL from Week 4 through Week 24. Baseline PB use was a prespecified study subgroup of interest. The difference in mean Hgb values at Week 24 between treatment groups was summarized overall and by subgroup. Comparisons were performed for the Week 24 Hgb (post hoc), as well as the final dose of daprodustat, for those receiving/not receiving PB. Results The majority of HD subjects in this 24-week safety and efficacy study received PB at baseline; 136 of 177 (77%) of subjects on daprodustat and 33 of 39 (85%) of subjects on control were taking PBs, with comparable phosphate control at baseline [mean (±SD) phosphate: daprodustat 1.76 mmol/L (0.56); control 1.67 mmol/L (0.44)]. No meaningful difference in Hgb change from baseline (CFB) at Week 24 was noted between daprodustat and rhEPO groups (Table 1). Conclusion These results suggest that daprodustat can be taken without regard to the timing of PB administration. Results of the large, phase 3 dialysis study of daprodustat will be important to definitively confirm these initial observations.