Abstract: TH-PO983
Safety and Efficacy of Vadadustat Thrice Weekly in Patients with Anemia due to Dialysis-Dependent CKD
Session Information
- Anemia in CKD: Risk Factors, Practice Patterns, Therapies
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Toka, Hakan R., Nova Clinical Research, Bradenton, Florida, United States
- Luo, Wenli, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Ullah, Irfan, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Yang, Zhihui (Sunny), Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Zhang, Zhiqun, Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
- Burke, Steven K., Akebia Therapeutics Inc, Cambridge, Massachusetts, United States
Background
Vadadustat (VADA) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). This study investigated the efficacy and safety of conversion from the long-acting IV erythropoiesis-stimulating agent methoxy polyethylene glycol-epoetin beta (CERA; MIRCERA®) to oral VADA thrice weekly (TIW) for the maintenance treatment of anemia in patients with dialysis-dependent chronic kidney disease (DD-CKD).
Methods
This randomized (1:1:1), open-label, active-controlled, sponsor-blinded trial compared VADA, at starting doses of 600 mg and 900 mg TIW, and CERA treatment in patients with DD-CKD for up to 52 weeks. Primary and secondary endpoints were mean change in hemoglobin (Hb) from baseline to the primary evaluation period (PEP; weeks 20–26) and secondary evaluation period (SEP; weeks 46–52), respectively (noninferiority margin, −0.75 g/dL). Other key endpoints included the proportion of patients requiring red blood cell (RBC) transfusions during the PEP and those with Hb levels >11g/dL and 12g/dL. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported as primary safety endpoints.
Results
VADA TIW (n=304) was noninferior to CERA (n=152) for mean change in Hb from baseline during the PEP (least-squares mean difference: –0.33 g/dL; 95% CI: –0.53, –0.13) and SEP (–0.33 g/dL; 95% CI: –0.56, –0.09). The percentage of patients receiving RBC transfusions during the PEP was 3% for both groups. The proportion of patients with Hb levels >11g/dL and 12g/dL were lower in the VADA group (61.6% and 20.5%, respectively) vs the CERA group (78.2% and 30.6%, respectively). VADA and CERA had similar incidences of TEAEs and serious TEAEs. The proportion of patients with TEAEs resulting in death was 9% in the VADA group and 11% in the CERA group. The most common TEAEs were COVID-19 and diarrhea in both groups. Incidence of cardiac arrest was more common in the CERA group (7.3%) compared to the VADA group (1.7%). No differences in abnormal liver enzymes were observed between treatment groups.
Conclusion
VADA TIW was noninferior to CERA in Hb efficacy. VADA had a lower proportion of patients with Hb excursions compared to CERA. The incidence of TEAEs and serious TEAEs was similar between VADA and CERA.
Funding
- Commercial Support – Akebia Therapeutics, Inc.