Kidney Week

Abstract: TH-PO908

Long-Term Safety of Vadadustat for Treatment of Anemia-Related CKD in Phase 3 Trials

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 Department 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

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

Kai-Uwe Eckardt, MD

• Koury, Mark, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Mark Koury, 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

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

Eldrin F. Lewis, MD

Background

Vadadustat (VADA) is an oral HIF-PHI for treating anemia in CKD. In a safety analysis from the VADA phase 3 clinical program, VADA had a similar safety profile to darbepoetin alfa (DA) over the course of treatment with respect to treatment-emergent adverse events (TEAEs) and TEAEs of special interest (TEAESIs), including cardiovascular, hepatic, retinal, and neoplasm-related AEs. The present analysis evaluated the long-term safety of VADA compared with DA in patients from the phase 3 VADA clinical program.

Methods

Safety data were pooled from four global phase 3 trials that compared the safety and efficacy of VADA and DA in patients with CKD (INNO₂VATE: incident dialysis-dependent [DD]-CKD [NCT02865850] or prevalent DD-CKD [NCT02892149]; PRO₂TECT: ESA-untreated [NCT02648347] or ESA-treated [NCT02680574] with non-DD [NDD]-CKD). We compared the long-term (≥2 years) risk of TEAESIs and serious TEAESIs for each treatment arm. TEAESIs were grouped by medical topic. Rate ratios and 95% CIs were calculated for each TEAESI to evaluate potential differences between treatment arms.

Results

In the global phase 3 program, 2634 patients had ≥2 years of treatment and follow-up (VADA, n=1305, total patient years [PY]=3426.7; DA, n=1329, total PY=3512.4). Baseline characteristics were similar. TEAESIs were observed in 625 (47.9%; 42.2 events per 100 PY) and 696 (52.4%; 46.2 events per 100 PY) patients treated with VADA and DA, respectively (Figure). The frequency of serious TEAESIs was similar between VADA (259 patients [19.8%]; 12.3 events per 100 PY) and DA (292 patients [22.0%]; 14.5 events per 100 PY).

Conclusion

The long-term (≥2 years) safety profile of VADA was similar to DA in a pooled population of patients with DD- or NDD-CKD-related anemia.

Figure. TEAESIs During Long-term Treatment. *Clear cell renal carcinomas were reported in 2 (0.2%) patients in the VADA group and 2 (0.2%) patients in the DA group.

Funding

• Commercial Support – Akebia Therapeutics, Inc.