Kidney Week

Abstract: SA-PO1097

Comparison Between Vadadustat Exposure (Cmax) and Major Adverse Cardiovascular Events in Patients with Dialysis-Dependent CKD

Session Information

• Kidney Replacement Therapy and Care Delivery Innovations
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 801 Dialysis: Hemodialysis and Frequent Dialysis

Authors

• Navarro Gonzales, Pamela C., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Pamela C. Navarro Gonzales, MS

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

Wenli Luo, MD, PhD

• Minga, Todd Eric, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Todd Eric Minga, MD

• Burke, Steven K., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Steven K. Burke, MD

• Dykstra, Kevin, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States

Kevin Dykstra, PhD

Background

Vadadustat (VADA) is approved in the US for once-daily (QD) dosing to treat anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least 3 months. While overall treatment effects on major adverse cardiovascular events (MACE) have been previously characterized, the relationship between VADA exposure, particularly peak concentration (C_max), and cardiovascular risk remains an important consideration, especially for three-times-weekly (TIW) dosing where a higher dose is given less frequently, to evaluate overall exposure (weekly area under the curve [AUC]) compared with QD dosing. Here, we evaluated whether VADA dose, AUC, or C_max is associated with an increased risk of MACE in patients with dialysis-dependent (DD)-CKD.

Methods

The VADA phase 3 trials (INNO₂VATE, MO₂DIFY, and FO₂CUS) included adult patients who were receiving dialysis for at least 12 weeks prior to screening. Time-to-event analyses were conducted in VADA-treated patients from phase 3 trials evaluating QD and TIW dosing. Individual weekly C_max values were derived via population pharmacokinetic modeling and empirical Bayes estimates under steady-state assumptions, then time-averaged over treatment duration (or until event). To examine a potential relationship between VADA concentration and risk of MACE, C_max was categorized into quartiles within each regimen, and the highest quartile (Q4) was compared with lower quartiles (Q1–Q3). Cox proportional hazards models were used to evaluate associations with MACE, adjusting for demographic and clinical covariates, baseline erythropoiesis-stimulating agent (ESA) dose, and time-averaged VADA dose.

Results

A total of 2362 VADA-treated patients from phase 3 trials had pharmacokinetic data available (QD, n=1958; TIW, n=404). For QD dosing, C_max (μg/mL) ranged from 47.84 to 281.04 in Q4 and from 0.02 to 47.70 in Q1–Q3. For TIW dosing, C_max ranged from 75.80 to 387.32 in Q4 and from 4.42 to 75.45 in Q1–Q3. No significant association was observed between higher VADA C_max quartile and MACE risk (Q4 vs Q1–Q3: estimate 0.19, SE 0.140; P=0.19). Age (P<0.001), history of previous cardiovascular events (P<0.001), and baseline ESA dose (P=0.02) were all associated with increased risk.

Conclusion

Overall, these results suggest VADA C_max was not associated with MACE risk in patients with DD-CKD, irrespective of dosing regimen.

Funding

• Commercial Support – Akebia Therapeutics, Inc.