Abstract: TH-OR047
Win-Odds Analysis of Deaths and Hospitalization in Patients Taking Vadadustat or Darbepoetin Alfa for CKD-Related Anemia Undergoing Dialysis
Session Information
- Hemodialysis: Novel Interventions
November 06, 2025 | Location: Room 351D, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States
- Agarwal, Rajiv, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Burke, Steven K., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Minga, Todd Eric, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Sarnak, Mark J., Tufts University School of Medicine, Boston, Massachusetts, United States
- Winkelmayer, Wolfgang C., Baylor College of Medicine, Houston, Texas, United States
- Eckardt, Kai-Uwe, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany
Background
Vadadustat (VADA) is an oral HIF-PHI for treating anemia in CKD. In the phase 3 INNO2VATE trials, VADA was noninferior to darbepoetin alfa (DA) for cardiovascular safety ([MACE; a composite endpoint of death from any cause, nonfatal myocardial infarction, or nonfatal stroke], HR 0.96; 95% CI, 0.83–1.11). The primary time to event analysis does not use a hierarchy of clinical priorities, and only accounts for the first event, not recurrent events. Therefore, we employed a post-hoc win odds analysis that prioritizes all-cause mortality and accounts for multiple hospitalizations to further understand these important clinical priorities in the context of treatment with VADA or DA.
Methods
The INNO2VATE trials were open-label active-controlled trials in adult patients with CKD-related anemia on dialysis, randomized 1:1 to receive VADA or DA. In this win-odds analysis, the hierarchy for the components was 1) time to all-cause mortality (ACM) and 2) exposure adjusted all-cause hospitalizations (HOSP) [ACM+HOSP]. The win-odds was calculated as the number of wins in DA group plus half of the ties divided by the number of wins in VADA group plus half of the ties. Safety analyses were conducted among all randomized patients who received at least one dose of study drug.
Results
There were 1947 patients randomized to VADA and 1955 patients randomized to DA. The incidence of ACM was 14.9% (291/1947) for VADA and 15.9% (310/1955) for DA. The incidence of HOSP was 50.6% (986/1947) for VADA and 53.9% (1053/1955) for DA. For the composite ACM+HOSP, the win count in the DA group was 1,435,594 and the win count in the VADA group was 1,576,345, with 794,446 ties. The win odds (95% CI) for VADA compared to DA was 0.93 (0.87–0.99; p=0.03).
Conclusion
In a post-hoc analysis, the composite of all-cause mortality and hospitalizations was statistically significantly lower for VADA compared to DA in a win-odds analysis among patients with DD- CKD.
Funding
- Commercial Support – Akebia Therapeutics, Inc.