Abstract: TH-PO1197
Model-Based Vadadustat Starting Dose Recommendations in Patients with Dialysis-Dependent CKD
Session Information
- Late-Breaking Research Posters
November 06, 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
- Dykstra, Kevin, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Clary, James A, Allucent US LLC, Cary, North Carolina, United States
- Navarro Gonzales, Pamela C., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Roberts, Jessica K, Allucent US LLC, Cary, North Carolina, United States
Background
Vadadustat (VADA) is an oral hypoxia inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for treatment of CKD anemia. In Phase 3 trials, many patients experienced an initial hemoglobin (Hb) decline after switching from an ESA at starting VADA doses of 300 mg daily (QD) or 600-900mg thrice weekly (TIW). Patients with lower baseline (bl) Hb or with higher bl ESA dose were more likely to experience Hb falling below 9.5 g/dL before returning to pre-dose levels. We used modeling to explore alternative dosing strategies based on bl Hb and ESA dose to ameliorate initial Hb decline.
Methods
We developed a PK/PD model linking Hb response to VADA dose using data from 5 Phase 2 trials (N=463) and 8 Phase 3 trials (N=2359) including patients treated with QD and TIW dosing regimens. Simulations were performed in virtual dialysis-dependent patients with bl characteristics of interest (ESA experienced/naïve, bl Hb ≥ or <10 g/dL, and bl standardized ESA dose ≥ or < 90 IU/kg/wk Epogen equivalents). We tested QD starting doses of 150, 300, 450, and 600 mg or TIW doses of 300, 600, 900 and 1200 mg, and predicted Hb response vs. time for each virtual patient. Results were summarized across patients over time to find the regimen(s) minimizing the magnitude and duration of initial Hb decline.
Results
Treatment objectives were to keep Hb levels >9.5 g/dL for transfusion avoidance, while minimizing excursions above 12 g/dL (US target Hb range of 10-11g/dL). Because VADA is titrated to effect, the long-term Hb response is independent of starting dose for all patients. A QD starting dose of 450 mg or 900 mg TIW minimized the initial decline in Hb and accelerated the return to the target range in most patients (Figure). Patients with higher bl Hb or lower prior ESA dose were more likely to achieve satisfactory Hb response at a lower VADA starting dose.
Conclusion
A VADA starting dose of 450 mg QD or 900 mg TIW should ameliorate the transitory decline in Hb following a switch from ESA in most patients.
Simulated Hb vs. Time by VADA Starting Dose
Funding
- Commercial Support – Akebia Therapeutics, Inc.