Kidney Week

Abstract: PO0457

Iron-Related Outcomes in Patients with Dialysis-Dependent CKD Randomized to Vadadustat vs. Darbepoetin Alfa

Session Information

• Anemia: Therapies and Iron Metabolism
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Winkelmayer, Wolfgang C., Baylor College of Medicine, Houston, Texas, United States

Wolfgang C. Winkelmayer, MD, FASN

• Fishbane, Steven, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States

Steven Fishbane,

• Tumlin, James A., Emory University School of Medicine, Atlanta, Georgia, United States

James A. Tumlin,

• Farag, Youssef MK, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Youssef MK Farag,

• Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Wenli Luo,

• Anders, Robert, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Robert Anders,

• Solinsky, Christine, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Christine Solinsky,

• Vargo, Dennis, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Dennis Vargo,

• Koury, Mark, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Mark Koury,

Background

Vadadustat (VADA) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being investigated for treatment of anemia due to chronic kidney disease (CKD).

Methods

We conducted 2 global phase 3, randomized, open-label, active-controlled, noninferiority trials (INNO₂VATE) comparing once-daily oral dosing of VADA with the erythropoiesis-stimulating agent darbepoetin alfa (DA) in patients with anemia and incident (N=369) or prevalent (N=3554) dialysis-dependent (DD) CKD. Inclusion criteria: serum ferritin ≥100 ng/mL and transferrin saturation (TSAT) ≥20%. Safety and efficacy results of the INNO₂VATE trials were previously reported. Here we report iron-related outcomes, including the changes in mean serum hepcidin, ferritin, total iron-binding capacity (TIBC), iron, and TSAT from baseline to the primary (wk 24–36) and secondary (wk 40–52) evaluation periods.

Results

A total of 1958 patients received VADA and 1965 received DA. VADA treatment was associated with greater decreases in mean hepcidin and ferritin, and increases in TIBC from baseline to the primary and secondary evaluation periods (Table). Mean serum iron decreased more in the DA than the VADA group from baseline to wk 24–36 and 40–52. Oral and intravenous iron use was similar in the 2 treatment groups throughout both studies. Similar results were seen in the non–DD-CKD populations (PRO₂TECT studies).

Conclusion

The observed relative decreases in hepcidin and ferritin and the increase in TIBC are consistent with a VADA-induced facilitation of iron mobilization from intracellular stores that support erythropoiesis.

Funding

• Commercial Support – Akebia Therapeutics, Inc., and Otsuka Pharmaceuticals Development and Commercialization, Inc.