Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis

Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA. Indiana University School of Medicine, Indianapolis, IN, USA. Medical School, University of Western Australia, Perth, Australia. Peritoneal Dialysis Center of America, Montebello, CA, USA. Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany. PI Health, Montebello, CA, USA. Colorado Kidney Care, Denver, CO, USA. Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. Pennsylvania Nephrology Associates, Philadelphia, PA, USA. Akebia Therapeutics, Inc., Cambridge, MA, USA. Memorial University, St. John's, NL, Canada. Baylor College of Medicine, Houston, TX, USA. Stanford University School of Medicine, Palo Alto, CA, USA.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2023

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BACKGROUND Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear. METHODS We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary efficacy period (weeks 24-36). RESULTS Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups (hazard ratio 1.10; 95% CI 0.62, 1.93). In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was -0.10 g/dL (95% CI -0.33, 0.12) in the primary efficacy period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively. CONCLUSIONS In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.
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Language : eng
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