Two long-term phase 3 studies of enarodustat (JTZ-951) in Japanese anemic patients with chronic kidney disease not on dialysis or on maintenance hemodialysis: SYMPHONY ND-Long and HD-Long studies.

Published on Aug 13, 2021in Therapeutic Apheresis and Dialysis1.762
· DOI :10.1111/1744-9987.13724
Tadao Akizawa65
Estimated H-index: 65
(Showa University),
Masaomi Nangaku84
Estimated H-index: 84
(UTokyo: University of Tokyo)
+ 4 AuthorsHideki Hirakata59
Estimated H-index: 59
Sources
Abstract
Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease. Two open-label, uncontrolled phase 3 studies evaluated the 52-week safety and efficacy of enarodustat in Japanese anemic patients with chronic kidney disease not on dialysis (n = 132) [SYMPHONY ND-Long study] or on maintenance hemodialysis (n = 136) [SYMPHONY HD-Long study]. The most frequent adverse events were viral upper respiratory tract infection (25.8%) followed by chronic kidney disease (8.3%) in the SYMPHONY ND-Long study, and viral upper respiratory tract infection (49.3%) followed by contusion (16.9%) and diarrhea (16.9%) in the SYMPHONY HD-Long study. The incidence of any adverse events did not increase over time. Mean hemoglobin levels and 95% confidence intervals were maintained within the target range (10.0-12.0 g/dL) over 52 weeks in both studies. The long-term safety and efficacy of enarodustat were confirmed in Japanese anemic patients with chronic kidney disease. This article is protected by copyright. All rights reserved.
References23
Newest
#1Tadao Akizawa (Showa University)H-Index: 65
#2Masaomi Nangaku (UTokyo: University of Tokyo)H-Index: 84
Last. Hideki HirakataH-Index: 59
view all 7 authors...
Abstract Introduction Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that might be a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy (non-inferiority to darbepoetin alfa [DA]) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis. Methods Erythropoiesis-stimulating agent (ESA)-naive patients and ESA-treated patients were randomized at a 1:1 ratio to receiv...
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#1Tadao AkizawaH-Index: 4
#2Masaomi NangakuH-Index: 84
Last. Hideki HirakataH-Index: 59
view all 7 authors...
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#1Mark R. Hanudel (UCLA: University of California, Los Angeles)H-Index: 10
#2Michele F Eisenga (UMCG: University Medical Center Groningen)H-Index: 15
Last. Tomas Ganz (UCLA: University of California, Los Angeles)H-Index: 159
view all 17 authors...
BACKGROUND: Erythropoietin (EPO) has been reported as a novel determinant of fibroblast growth factor 23 (FGF23) production; however, it is unknown whether FGF23 is stimulated by chronic exposure to EPO or by EPO administration in nonpolycystic chronic kidney disease (CKD) models. METHODS: We analyzed the effects of chronic EPO on FGF23 in murine models with chronically high EPO levels and normal kidney function. We studied the effects of exogenous EPO on FGF23 in wild-type mice, with and withou...
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#1Tadao Akizawa (Showa University)H-Index: 65
#2Masaomi Nangaku (UTokyo: University of Tokyo)H-Index: 84
Last. Hideki HirakataH-Index: 59
view all 8 authors...
Background: Enarodustat (JTZ-951) is an orally available hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin levels in the treatment of anemia associated with chronic kidney disease (CKD). Objective: A phase 2b study of enarodustat to assess the hemoglobin (Hb) response, safety, and maintenance dosage was conducted in Japanese anemic patients with hemodialysis-dependent CKD. Methods: Subjects receiving a stable dose of an erythropoiesis-stimulating agen...
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#1Midori Sakashita (UTokyo: University of Tokyo)H-Index: 2
#2Tetsuhiro Tanaka (UTokyo: University of Tokyo)H-Index: 38
Last. Masaomi Nangaku (UTokyo: University of Tokyo)H-Index: 84
view all 3 authors...
BACKGROUND: Hypoxia-inducible factor (HIF) stabilizers, also known as inhibitors of HIF prolyl hydroxylase domain (PHD) inhibitors enzymes, are novel small-molecule agents to treat renal anemia. They increase endogenous erythropoietin (EPO) production by stabilizing HIF. This review focuses on the mechanisms by which PHD inhibitors ameliorate anemia in chronic kidney disease (CKD) and summarizes the current clinical experience with and prospects for these drugs. SUMMARY: Anemia is a serious comp...
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#1Tadao Akizawa (Showa University)H-Index: 65
#2Masaomi Nangaku (UTokyo: University of Tokyo)H-Index: 84
Last. Hideki HirakataH-Index: 59
view all 7 authors...
BACKGROUND: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that mimics adaptive responses to hypoxic conditions and may provide a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy, safety, and maintenance dose of enarodustat in anemic patients with CKD not on dialysis. METHODS: Erythropoiesis-stimulating agent (ESA) naive patients (correction group) and patients on a stable dose of ESA (co...
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#1Mark R. Hanudel (UCLA: University of California, Los Angeles)H-Index: 10
#2Marciana Laster (UCLA: University of California, Los Angeles)H-Index: 6
Last. Isidro B. Salusky (UCLA: University of California, Los Angeles)H-Index: 66
view all 3 authors...
Purpose of Review We will review non-renal-related mechanisms of fibroblast growth factor 23 (FGF23) pathophysiology.
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#1Yosuke Ogoshi (JT: Japan Tobacco)H-Index: 4
#2Takuya Matsui (JT: Japan Tobacco)H-Index: 3
Last. Hiroyuki Abe (JT: Japan Tobacco)H-Index: 7
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Inhibition of hypoxia inducible factor prolyl hydroxylase (PHD) represents a promising strategy for the discovery of a next generation treatment for renal anemia. We identified several 5,6-fused ring systems as novel scaffolds of the PHD inhibitor on the basis of pharmacophore analysis. In particular, triazolopyridine derivatives showed potent PHD2 inhibitory activities. Examination of the predominance of the triazolopyridines in potency by electrostatic calculations suggested favorable π–π stac...
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#1Ingo Flamme (Bayer)H-Index: 5
#2Peter Ellinghaus (Bayer)H-Index: 9
Last. Thilo Krüger (Bayer)H-Index: 2
view all 4 authors...
Plasma levels of FGF23 are increased in patients with chronic kidney disease. Beside its role in phosphate homeostasis, iron deficiency and anemia are associated with increased FGF23 plasma levels. Recently, FGF23 plasma levels were shown to be increased in mice after treatment with hypoxia inducible factor-proline hydroxylase (HIF-PH) inhibitors which are strong inducers of erythropoietin and erythropoiesis and are known to modulate iron uptake and availability. Therefore we investigated a pote...
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#1Hiroyasu YamamotoH-Index: 20
#2Shinichi Nishi (Kobe University)H-Index: 48
Last. Hirokazu Honda (Showa University)H-Index: 16
view all 19 authors...
Renal anemia is a complication of chronic kidney disease. Guidelines for safe and effective treatment in patients with renal anemia are needed. The Japanese Society for Dialysis Therapy (JSDT) published guidelines for the treatment of renal anemia in chronic hemodialysis patients in 2004 and in hemodialysis, peritoneal dialysis, predialysis, and pediatric patients in 2008. These two publications provide excellent guidance with respect to clinical practice issues, including the definition and dia...
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Cited By1
Newest
Anemia is a common feature and complication of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) and recombinant human erythropoietin have been used widely in renal anemia treatment. Recently, hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs) that may improve the treatment of renal anemia patients were launched. Previous studies indicated that HIF-PHIs may decrease hepcidin levels and modulate iron metabolism, thereby increasing total iron-binding capa...
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#1Bartłomiej Borawski (Medical University of Warsaw)
#2Jacek S. MalyszkoH-Index: 31
Last. Jolanta MalyszkoH-Index: 35
view all 4 authors...
Chronic kidney disease (CKD) is one of the fastest-growing major causes of death internationally. Better treatment of CKD and its complications is crucial to reverse this negative trend. Anemia is a frequent complication of CKD and is associated with unfavorable clinical outcomes. It is a devastating complication of progressive kidney disease, that negatively affects also the quality of life. The prevalence of anemia increases in parallel with CKD progression. The aim of this review is to summar...
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