Abstract: FR-PO0202
Consistency of the Estimate of Responsiveness of Vadadustat vs. Darbepoetin
Session Information
- Anemia and Iron Metabolism
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Chait, Yossi, University of Massachusetts Amherst, Amherst, Massachusetts, United States
- Nathanson, Brian Harris, OptiStatim, LLC, Longmeadow, Massachusetts, United States
- Germain, Michael J., Holyoke Medical Center, Holyoke, Massachusetts, United States
Background
Heterogeneous responses to ESAs make maintaining target hemoglobin (Hb) levels challenging, as Hb variability—affected by factors such as iron status—has been associated with adverse outcomes. Model-based, personalized anemia management can reduce this variability. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) stimulate endogenous erythropoietin and improve iron use, even during inflammation. We assessed the consistency of a personalized responsiveness metric in patients treated with either ESA or HIF-PHI therapy.
Methods
The cohort included non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients from Phase 3 Vadadustat trials. Responsiveness was retrospectively estimated from drug dose and Hb levels over 10-week windows, recalculated with a one-week forward shift. Following an 8-week washout, patients with ≥9 weeks of data were included. Responsiveness and dosage were z-score normalized. A panel data linear regression with patient-clustered robust standard errors modeled responsiveness by drug type and dose. Adjusted mean responsiveness standard deviations (SDs) were compared using a two-sample test for equality of variance.
Results
Over the 10-week post-washout period, patients treated with Vadadustat demonstrated a significantly lower adjusted SD of the responsiveness coefficient of variation than those receiving Darbepoetin (Figure 1; NDD: 1.41 vs. 2.23, p < 0.001; DD: 0.987 vs. 2.195, p < 0.001). This trend persisted when responsiveness was assessed in subsequent 10-week periods later in the trials (Table 1).
Conclusion
Lower responsiveness variability in NDD and DD Vadadustat-treated patients suggests more precise Hb control, supporting the potential of a personalized dosing algorithm to improve anemia management.
Normalized responsiveness histograms: Darbepoetin vs. Vadadustat in NDD and DD trials
Table 1: Adjusted standard deviations of responsiveness
Funding
- Commercial Support – Akebia Therapeutics, Inc.