Kidney Week

Abstract: TH-PO907

Safety and Efficacy of Vadadustat in Erythropoiesis-Stimulating Agent-Naïve Patients New to Dialysis Who Have CKD-Related Anemia

Session Information

• Anemia and Iron Metabolism
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States

Glenn M. Chertow, MD, MPH, FASN

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

Steven K. Burke, MD

• Lewis, Eldrin F., Stanford University School of Medicine, Stanford, California, United States

Eldrin F. Lewis, MD

• 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

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak, MD, MS

• Eckardt, Kai-Uwe, Charite Universitatsmedizin Berlin, Berlin, Germany

Kai-Uwe Eckardt, MD

Background

Vadadustat (VADA) is an oral HIF-PHI for treating anemia in CKD. In the phase 3 incident INNO₂VATE trial in patients new to dialysis, VADA was noninferior to the ESA darbepoetin alfa (DA) for hemoglobin (Hb) efficacy, with a similar safety profile. Since this trial enrolled patients with and without prior ESA use, post hoc analyses of patients previously naïve to ESAs were conducted to better understand efficacy and safety of VADA in this subgroup.

Methods

A post hoc analysis of the incident INNO₂VATE trial (N=369; NCT02865850) assessed the efficacy and safety of VADA compared to DA in ESA-naïve patients. Primary and secondary efficacy endpoints were mean change in Hb from baseline to the primary (PEP, weeks 24-36) and secondary (SEP, weeks 40-52) evaluation periods, respectively (noninferiority margin [lower bound of the 95% CI] of −0.75 g/dL). Other endpoints included the proportion of patients requiring ESA rescue and those with Hb levels >12g/dL and <9g/dL. Treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and TEAEs leading to death were reported as safety endpoints.

Results

In the incident INNO₂VATE trial, 192 patients were ESA naïve (VADA, n=89; DA, n=103). A majority (VADA, n=58 [65.2%]; DA, n=66 [64.1%]) had Hb <9.5 g/dL. In ESA-naïve patients, VADA was noninferior to DA for Hb efficacy during the PEP (LS mean treatment difference, -0.13; 95% CI, -0.44 to 0.18) and SEP (LS mean treatment difference, 0.05; 95% CI, -0.30 to 0.40). ESA rescue therapy was similar, with 9.0% and 10.6% (PEP) and 6.2% and 7.2% (SEP) of patients receiving it in the VADA and DA groups, respectively. Hb excursions >12.0 g/dL were more common in the VADA group (PEP, 25.6%; SEP, 30.4%) than the DA group (PEP, 18.9%; SEP, 21.2%). Hb concentrations <9.0 g/dL were seen with similar frequency in the VADA and DA groups during the PEP (VADA, 23.1%; DA, 18.9%) and SEP (VADA, 24.6%; DA, 28.2%). Safety endpoints were seen with similar frequency between treatment groups: TEAEs (VADA, 79.5%; DA, 86.3%), SAEs (VADA, 51.1%; DA, 57.8%), TEAEs leading to death (VADA, 11.4%; DA, 9.8%).

Conclusion

In this post hoc analysis of ESA-naïve patients new to dialysis with CKD-related anemia, VADA was noninferior to DA for efficacy and had a similar safety profile.

Funding

• Commercial Support – Akebia Therapeutics, Inc.