• Masaomi Nangaku, FaragYoussef M KYMKClinical Development, Akebia Therapeutics Inc., Cambridge, MA, USA., Emil deGoma, Wenli Luo, Dennis Vargo, and Zeeshan Khawaja.
• Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
• Nephrol. Dial. Transplant. 2020 Jul 28.

BackgroundVadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic kidney disease (CKD)-induced anemia.MethodsTwo Phase 2, multicenter, double-blind, placebo-controlled studies randomized Japanese patients with nondialysis-dependent (NDD, n = 51) or dialysis-dependent (DD, n = 60) CKD-induced anemia to once-daily vadadustat (150, 300 or 600 mg) or placebo. A 6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat dose adjustment/maintenance period. The primary endpoint was the mean change in hemoglobin (Hb) level from pretreatment to Week 6.ResultsStatistically significant (P < 0.01) dose-dependent increases in mean Hb values were observed at Week 6 in all vadadustat groups versus placebo [placebo and vadadustat 150, 300 and 600 mg: -0.47, 0.43, 1.13 and 1.62 (NDD-CKD) and -1.48, -0.28, 0.08 and 0.41 (DD-CKD), respectively]. By Week 16, 91% (NDD-CKD) and 71% (DD-CKD) of vadadustat-treated participants achieved target Hb levels (10.0-12.0 g/dL) and significant dose-dependent changes in iron utilization and mobilization biomarkers were observed with vadadustat. During the primary efficacy period, the incidence of treatment-emergent adverse events (AEs) with placebo and vadadustat 150, 300 and 600 mg was 36, 33, 58 and 54% (NDD-CKD) and 40, 53, 73 and 40% (DD-CKD), respectively. The most common AEs during the primary efficacy period were nausea and hypertension (NDD-CKD) and diarrhea, nasopharyngitis and shunt stenosis (DD-CKD). Of 23 serious AEs in 18 patients, 1 was deemed related (hepatic function abnormal); no deaths were reported.ConclusionsThe efficacy and safety results from these studies support the development of vadadustat for the treatment of anemia in patients with CKD.© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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