Vadadustat, an investigational oral inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain proteins (HIF-PHDs), can maintain mean hemoglobin (Hb) within target range for hemodialysis (HD) patients, according to new study findings.
In an online report published by Nephrology Dialysis Transplantation, Peter McCullough, MD, MPH, of Baylor University Medical Center in Dallas, and colleagues presented data from a 16-week, phase 2 trial of vadadustat in 94 HD patients with anemia previously controlled with epoetin alpha therapy. After halting the erythropoiesis-stimulating agent, patients received vadadustat starting doses of 300 mg once daily, 450 mg once daily, or 450 mg thrice weekly with titration up to 600 mg daily after week 8.
Results showed no statistically significant change in mean Hb from pre-baseline levels. Mean Hb remained relatively stable through weeks 7 and 16 of the trial. Just one patient had an Hb excursion above 13 g/dL. Whether vadadustat improves iron metabolism requires further study.
The vast majority of patients (83%) experienced an adverse event. Nausea (11.7%), diarrhea (10.6%), and vomiting (9.6%) were the most common. Although serious adverse events occurred, none were related to vadadustat use.
“Given its effects on erythropoiesis and preliminary safety profile, vadadustat has the potential to provide an alternative to conventional ESA therapy for the treatment of anemia secondary to CKD,” Dr McCullough and the team stated. Additional studies are needed to assess vadadustat’s long-term safety and efficacy.
The study was funded by Akebia Therapeutics, the makers of vadadustat. Several authors disclosed financial relationships or employment with the company.
Haase VH, Chertow GM, and Block GA. Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents. Nephrol Dial Transplant 2018;1–10. doi: 10.1093/ndt/gfy055