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Kidney Week

Abstract: TH-PO690

Maximal Change in Erythropoietin in Hemodialysis Patients Receiving Daprodustat or Epoetin Alfa in the ASCEND-TD Trial

Session Information

  • Anemia and Iron Metabolism
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Coyne, Daniel W., Washington University School of Medicine, St. Louis, Missouri, United States
  • Wanner, Christoph, University of Würzburg, Würzburg, Germany
  • Lopes, Renato D., Duke University Medical Center, Durham, North Carolina, United States
  • Bailey, Christine K., GSK, Collegeville, Pennsylvania, United States
  • Mahar, Kelly M., GSK, Collegeville, Pennsylvania, United States
  • Shannon, Jennifer, GSK, Collegeville, Pennsylvania, United States
  • Singh, Ajay K., Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
Background

Higher erythropoiesis-stimulating agent (ESA) doses correlate with morbidity in patients treated for anemia of chronic kidney disease. Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, corrects anemia by inducing endogenous erythropoietin (EPO). Changes in EPO and vascular endothelial growth factor (VEGF) were examined in a double-blind trial of daprodustat vs epoetin alfa (epoetin) in hemodialysis patients.

Methods

407 patients on ESA (baseline hemoglobin [Hb] 8–11.5 g/dL) were randomized 2:1 to daprodustat 3-times-weekly (TIW) or epoetin once-weekly or TIW for 52 weeks (ASCEND-TD, NCT03400033). The primary endpoint (change in Hb) was met and safety profiles were similar. Plasma EPO and VEGF were measured pre-dose on day 1 and once during weeks 28–52, pre-dose and 2, 4, 6, or 8h post-dose. Major adverse cardiovascular events (MACE) were adjudicated.

Results

Mean ± standard deviation (SD) baseline EPO levels (IU/L) were low (22 ± 45 daprodustat vs 18 ± 22 epoetin). Maximal (max) mean EPO increases across all doses were lower with daprodustat (161 ± 362) vs epoetin (12313 ± 814). Higher daprodustat and epoetin doses mostly correlated with max EPO (Figure); max post-baseline and change from baseline EPO with higher daprodustat doses (20–48mg) were similar to or lower than for the lowest epoetin dose (1500U). VEGF levels declined from baseline for daprodustat and epoetin, unrelated to dose. Daprodustat dose was not related to occurrence of first MACE; mean ± SD dose at first MACE (14.6 ± 9.5mg) was similar to final dose without MACE (17.2 ± 13.7mg).

Conclusion

Daprodustat-induced changes in EPO were dose-dependent. Despite high daprodustat doses, the EPO levels produced were similar to levels seen at the lowest epoetin doses.

Figure. Summary of EPO, IU/L, maximal change from baseline for daprodustat (A) and epoetin alfa (B)

Funding

  • Commercial Support