A phase 3, open-label, single-arm study of vadadustat for anemia in chronic kidney disease for Japanese patients on hemodialysis not receiving erythropoiesis-stimulating agents

Masaomi Nangaku, Kazuoki Kondo, Souichirou Takabe, Kiichiro Ueta, Tsubasa Tandai, Yutaka Kawaguchi, Yasuhiro Komatsu, Masaomi Nangaku, Kazuoki Kondo, Souichirou Takabe, Kiichiro Ueta, Tsubasa Tandai, Yutaka Kawaguchi, Yasuhiro Komatsu

Abstract

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in Japan for the treatment of anemia in patients with chronic kidney disease (CKD). This phase 3, open-label, single-arm study evaluated the efficacy and safety of vadadustat in 24 Japanese patients with CKD-associated anemia on hemodialysis who were not receiving erythropoiesis-stimulating agents (ESAs). Patients received vadadustat for 24 weeks; the starting dose was 300 mg/day and doses were adjusted to achieve the target hemoglobin (Hb) range of 10.0-12.0 g/dL. The least squares mean of average Hb at Weeks 20 and 24 (95% confidence interval) was 10.75 g/dL (10.35, 11.14). The most common adverse event was shunt stenosis (25.0%). Adverse drug reactions (diarrhea and vomiting) occurred in two patients (8.3%) and the severity was mild. Vadadustat increased and maintained Hb levels within the target range and was generally well-tolerated in Japanese patients with anemia on hemodialysis not receiving ESAs.

Keywords: anemia; chronic kidney disease; hemodialysis; hypoxia-inducible factor prolyl hydroxylase inhibitor; vadadustat.

Conflict of interest statement

Masaomi Nangaku has received honoraria, advisory fees, or research funding from Akebia, Alexion, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, GSK, JT, Kyowa Hakko Kirin, Mitsubishi Tanabe, Ono, Takeda, and Torii. Yasuhiro Komatsu has received honoraria from Baxter, Chugai, and Kyowa Hakko Kirin. Kazuoki Kondo, Souichirou Takabe, Kiichiro Ueta, Tsubasa Tandai, and Yutaka Kawaguchi are employees of Mitsubishi Tanabe Pharma Corporation.

© 2021 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Figures

FIGURE 1
FIGURE 1
Patient flow diagram. a Treatment was discontinued because blood transfusion was necessary to improve hemoglobin level. b Although 21 patients completed the study, two of these were excluded from the efficacy analysis because they received rescue therapy
FIGURE 2
FIGURE 2
Average hemoglobin over time (full analysis set). Data are means with 95% confidence intervals. The shaded area indicates the target range. LOCF, last observation carried forward
FIGURE 3
FIGURE 3
Proportion of patients at each visit with hemoglobin levels above, within, or below the target range (full analysis set)
FIGURE 4
FIGURE 4
Change in iron‐related measures and red blood cell indices over time (full analysis set). (a) Serum iron, (b) TIBC, (c) TSAT, (d) serum ferritin, (e) Hepcidin, (f) MCV, (g) MCH, (h) MCHC, (i) RDW, (j) IV iron. Asterisks indicate a significant difference from baseline (paired t‐test; *p < 0.05; **p < 0.01). Data are means with 95% confidence intervals. BL, baseline; IV, intravenous; LOCF, last observation carried forward; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; RDW, red cell distribution width; TIBC, total iron binding capacity; TSAT, transferrin saturation; WK, week

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