Kidney Week

Abstract: SA-PO1096

Comparison of Major Adverse Cardiovascular Events with Once-Daily vs. Three-Times-Weekly Vadadustat Dosing 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 an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved to treat anemia in adult patients with chronic kidney disease (CKD) who have been on dialysis for at least 3 months. It is approved for once-daily (QD) administration. In the phase 3 INNO₂VATE trials, VADA was noninferior to darbepoetin alfa for time to first major adverse cardiovascular event (MACE, a composite endpoint of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke). Three-times-weekly (TIW) dosing, which aligns with the typical hemodialysis schedule, has been evaluated in two phase 3 trials (MO₂DIFY and FO₂CUS) with efficacy and safety findings comparable to QD dosing; however, TIW is not currently an approved dosing regimen for VADA. Here, we compared the cardiovascular safety of QD vs TIW dosing in the VADA phase 3 trials.

Methods

The VADA phase 3 trials included adult patients who were receiving dialysis for at least 12 weeks prior to screening. Time-to-event analyses for MACE were conducted using integrated data from phase 3 trials, including INNO₂VATE (safety population, n=3902) as well as MO₂DIFY and FO₂CUS (together, n=768). Cox proportional hazards models were used to evaluate the association between QD and TIW treatment regimens of VADA and MACE, adjusting for demographic and clinical covariates, baseline erythropoiesis-stimulating agents (ESA) dose, time-averaged VADA dose, and maximum concentration (C_max) quartiles.

Results

When comparing the time to MACE data for patients receiving QD or TIW dosing, there was no evidence of an increased risk of MACE with TIW dosing compared with QD dosing (P=0.924). Covariates associated with increased MACE risk included age (P<0.001) and prior cardiovascular history (P<0.001), while baseline ESA dose remained a significant predictor (P=0.017).

Conclusion

The risk of MACE was similar with TIW VADA dosing compared with QD dosing, supporting further evaluation of TIW dosing in patients with dialysis-dependent CKD.

Funding

• Commercial Support – Akebia Therapeutics, Inc.