Abstract
BACKGROUND: A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency. METHODS: DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0-11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10-12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16-24. The key secondary efficacy endpoint was the number of patients with hemoglobin response. RESULTS: The least square mean (standard error) change in hemoglobin from the baseline to week 16-24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: -0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa. CONCLUSION: In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India).