Vadadustat for Treatment of Anemia in Patients With Dialysis-Dependent Chronic Kidney Disease Receiving Peritoneal Dialysis

Authors

Mark J Sarnak
Rajiv Agarwal
Neil Boudville
Pradip C P Chowdhury
Kai-Uwe Eckardt
Carlos R Gonzalez
Laura A Kooienga
Mark J Koury
Kwabena A Ntoso
Wenli Luo
Patrick S Parfrey
Dennis L Vargo
Wolfgang C Winkelmayer
Zhiqun Zhang
Glenn M Chertow

Publication Date

9-29-2023

Journal

Nephrology Dialysis Transplantation

DOI

10.1093/ndt/gfad074

PMID

37096396

PMCID

PMC10539221

PubMedCentral® Posted Date

4-24-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Darbepoetin alfa, Renal Dialysis, Anemia, Renal Insufficiency, Chronic, Peritoneal Dialysis, Hematinics, Hemoglobins, Erythropoietin, anemia, chronic kidney disease, hypoxia-inducible factor prolyl hydroxylase inhibitor, peritoneal dialysis, vadadustat

Abstract

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 evaluation 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% confidence interval (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 evaluation 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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