Enaroy (enarodustat) / Japan Tobacco, JW Pharma, Shenzhen Salubris - LARVOL DELTA

REAL-WORLD ANEMIA MANAGEMENT BEFORE HEMODIALYSIS INITIATION IN JAPAN: A RETROSPECTIVE MULTICENTER COHORT STUDY (ISN-WCN 2026) - "ESA was used in 60%, HIF-PHIs in 30%, and no erythropoietic agents in 10%, with the following distribution: darbepoetin alfa 34%, epoetin beta pegol 26%, daprodustat 25%, roxadustat 3%, vadadustat 1%, and enarodustat 1%. In a multivariate logistic regression model adjusted for sex, age, and transferrin saturation, lower Hb 6 months prior was independently associated with Hb < 9 g/dL at HD initiation (p < 0.001), without significant differences between ESA and HIF-PHI groups.Conclusion Despite contemporary anemia therapy, 60% of patients presented with Hb < 10 g/dL and one-third with Hb < 9 g/dL at HD initiation. Lower baseline Hb strongly predicted suboptimal Hb control, suggesting that earlier dose adjustment and closer monitoring are warranted during progression to end-stage kidney disease."

Real-world • Real-world evidence • Retrospective data • Acute Kidney Injury • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Glomerulonephritis • Heart Failure • Hematological Disorders • Lupus Nephritis • Nephrology • Renal Disease • STAT3

The Efficacy and Safety of Enarodustat for the Treatment of Anemia in Hemodialysis Dependent Chronic Kidney Disease Patients: A Phase 3, Multicenter, Randomized, Active-Comparator (recombinant human erythropoietin), Open-Label Study：the ENARODIAL study. (PubMed, Am J Nephrol) - "Enarodustat was noninferior to rHuEPO for the treatment of anemia in HD-CKD patients , with good safety and tolerability over 24 weeks."

Journal • P3 data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Prospective, Multicenter, Randomized, Controlled, Double-Blind Study: Analysis of the Efficacy of Enarodustat in Treating Anemia in Patients with Renal Insufficiency due to Multiple Myeloma (ChiCTR) - P=N/A | N=154 | Not yet recruiting | Sponsor: The FIrst Affiliated Hospital, College of Medicine, Zhejiang University; The FIrst Affiliated Hospital, College of Medicine, Zhejiang University

New trial • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Nephrology • Oncology • Renal Disease

A Multicenter, Randomized, Positive Controlled Exploratory Study of Enadurestat in the Treatment of Renal Anemia in Diabetes Nephropathy (ChiCTR) - P4 | N=150 | Not yet recruiting | Sponsor: The Second Affiliated Hospital Zhejiang University School of Medicine; The Second Affiliated Hospital Zhejiang University School of Medicine

New P4 trial • Anemia • Diabetes • Diabetic Nephropathy • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease

A Phase 3 Study of Enarodustat in Chinese Patients Undergoing Peritoneal Dialysis for Treatment of Anemia: The ENAROPERA Study. (PubMed, Kidney Dis (Basel)) - "Enarodustat effectively maintained target Hb levels in PD patients with anemia, demonstrating favorable safety and tolerability. Its convenient once-daily oral dosing regimen may enhance patient adherence, highlighting its potential as a promising therapeutic option for anemia management in PD patients."

Journal • P3 data • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Prospective, Multicenter, Randomized, Controlled, Double-Blind Study: Analysis of the Efficacy and Safety of Enarodustat in Treating Anemia in Patients with Multiple Myeloma (ChiCTR) - P4 | N=82 | Not yet recruiting | Sponsor: The FIrst Affiliated Hospital, College of Medicine, Zhejiang University; The FIrst Affiliated Hospital, College of Medicine, Zhejiang University

New P4 trial • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Enarodustat suppresses thymic stromal lymphopoietin expression via hypoxia-inducible factor-mediated c-Jun N-terminal kinases dephosphorylation. (PubMed, PLoS One) - "Collectively, our findings identify a previously uncharacterized HIF-DUSP-JNK axis that negatively regulates TSLP expression. This study provides mechanistic insight into how HIF activation shapes epithelial cytokine responses, offering a basis for understanding the pathogenesis of TSLP-associated diseases such as atopic dermatitis."

IO biomarker • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • EPAS1 • HIF1A • MAPK8 • TLR2 • TSLP

Prolyl-hydroxylase domain inhibition enhances collagen levels in oral mucosa-derived fibroblasts. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "We examined three PHD inhibitors, IOX4, Enarodustat, and Daprodustat, for their effect on collagen levels in keratinized OMDFs. The mechanism involves HIF-1α-mediated upregulation of collagen-modifying enzymes. These findings highlight the potential of repurposing clinically approved PHD inhibitors as therapeutic agents for promoting the healing and regeneration of damaged gingiva and additional tissues."

Journal • HIF1A

Characterization of Novel Enarodustat Metabolites Using Liquid Chromatography-High Resolution Mass Spectrometry for Doping Control Purposes. (PubMed, Drug Test Anal) - "The study elucidates enarodustat's metabolic pathways and provides a foundation for developing sensitive detection methods. Future work should focus on synthesizing reference materials to identify metabolite structures."

Journal

Erythropoietin-Mimetic Peptide Pegmolesatide Therapy for Pure Red Cell Aplasia in a Patient with Nondialysis-Dependent Type 1 Diabetic Nephropathy: A Case Report (KIDNEY WEEK 2025) - "Enarodustat and roxadustat were administered successively after discontinuation of EPO, but anemia did not improve, and the patient was maintained with weekly blood transfusions...Discussion The new EPO-mimetic peptide pegmolesatide, which consists of 44 amino acids and has a completely different peptide chain structure from peginesatide and EPO (Fig 4), was independently developed in China...Thus, there is no cross-immune response between pegmolesatide and EPO. In addition, pegmolesatide rarely produces drug antibodies, attributed to the low immunogenicity.Based on these findings, we speculate that pegmolesatide can provide a safe, effective, and convenient therapeutic strategy for PRCA in Chinese patients with chronic kidney disease."

Case report • Clinical • Anemia • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hematological Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus

Effect and Mechanism of Enarodustat on Delaying Renal Interstitial Fibrosis by Mediating Aerobic Glycolysis (KIDNEY WEEK 2025) - "After interfering with HIF expression in HK-2 cells using shRNA, supplementation with JTZ-951 did not significantly improve the above phenomena. Conclusion JTZ-951 can inhibit the excessive activation of FOXK1 and the abnormally activated glycolysis, thereby delaying the progression of renal fibrosis."

Anemia • Cardiovascular • Chronic Kidney Disease • Fibrosis • Hematological Disorders • Immunology • Nephrology • Renal Disease • Reperfusion Injury • TGFB1

Profiling Inhibitor Scaffolds for the Cancer Target Jumonji-C Domain-Containing Protein 6. (PubMed, ChemMedChem) - "By contrast, some, but not all, clinically used inhibitors of the human hypoxia-inducible factor-α prolyl hydroxylase domain-containing proteins (PHDs) efficiently inhibit isolated JMJD6, in particular Enarodustat and Desidustat. The results identify attractive scaffolds for the development of selective, cell permeable JMJD6 inhibitors and suggest that JMJD6 inhibition is a potential off-target effect of PHD inhibitors in clinical use."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Discovery of enarodustat: A HIF prolyl hydroxylase inhibitor for the treatment of renal anemia (ACS-Fall 2025) - "As a result, we succeeded in identifying compound A bearing an [1,2,4]triazolo[4,3-a]pyridine core as a lead compound. Lead optimization to improve the efficacy of EPO release in cells and in vivo by improving cell permeability led to the discovery of enarodustat, with a 5-phenethyl substituent on the triazolopyridine group, which increased hemoglobin levels with daily oral dosing in rats."

Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

CANNON: Correction of Anemia With Enarodustat in Non-dialysis Dependent Chronic Kidney Disease (clinicaltrials.gov) - P4 | N=1670 | Recruiting | Sponsor: Shanghai Zhongshan Hospital | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2024 ➔ Mar 2025

Enrollment open • Trial initiation date • Anemia • Chronic Kidney Disease • Congestive Heart Failure • Hematological Disorders • Nephrology • Renal Disease

Enarodustat Tablets at Different Initial Doses for Anemia in Non-dialysis CKD Patients (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.

New P4 trial • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Lead Generation for a HIF Prolyl Hydroxylase Inhibitor: Discovery of (7-Hydroxy-[1,2,4]triazolo[1,5‑a]pyridine-8-carbonyl)glycine as a Lead Compound of Enarodustat. (PubMed, ACS Med Chem Lett) - "We successfully identified compound 21 bearing a [1,2,4]-triazolo-[4,3-a]-pyridine core as a lead compound. Structures of enarodustat and compound 21 differed only by the presence or absence of a phenethyl group, implying that the identification of a high-quality lead compound led to our success."

Journal • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Derivatives of the Clinically Used HIF Prolyl Hydroxylase Inhibitor Desidustat Are Efficient Inhibitors of Human γ-Butyrobetaine Hydroxylase. (PubMed, J Med Chem) - "We report that the clinically used hypoxia-inducible factor-α prolyl residue hydroxylase (PHD) inhibitors Desidustat, Enarodustat, and Vadadustat efficiently inhibit isolated recombinant BBOX, suggesting that BBOX inhibition by clinically used PHD inhibitors should be considered as a possible off-target effect. Structure-activity relationship studies on the Desidustat scaffold enabled development of potent BBOX inhibitors that manifest high levels of selectivity for BBOX inhibition over representative human 2OG oxygenases, including PHD2. The Desidustat derivatives will help to enable investigations into the biological roles of l-carnitine and the therapeutic potential of BBOX inhibition."

Journal • Cardiovascular

Pharmacokinetics, Pharmacodynamics, and Safety Evaluation of the Novel HIF-PH Inhibitor Enarodustat: An Open-Label Phase I Study in Healthy Chinese Participants. (PubMed, Clin Drug Investig) - "SAL-0951 was safe and well tolerated in healthy Chinese participants and had a linear pharmacokinetic profile. We found no ethnic differences in the pharmacokinetic characteristics of the drug between Chinese and Japanese populations."

Journal • P1 data • PK/PD data

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Non-Dialysis Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Indian J Nephrol) - "The studies included roxadustat (n = 2), daprodustat (n = 3), molidustat (n = 3), vadadustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Broadly, HIF-PHI molecules exhibited little difference when compared to other alternatives like erythropoietin stimulating agents (ESAs), but the evidence is not of high certainty. Our meta-analysis provides evidence on the use of HIF-PHIs as an alternative to ESAs for anemia in NDD-CKDs."

Journal • Retrospective data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Dialysis-Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Indian J Nephrol) - "The studies included roxadustat (n = 9), daprodustat (n = 5), vadadustat (n = 2), molidustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Roxadustat increased treatment-emergent adverse events up to 6-52 weeks as compared to ESAs [OR: 1.45 (95% CI 1.08-1.96); p = 0.01; six studies; 1715 participants; moderate certainty evidence]. The study provided evidence on the use of HIF-PHIs for treating renal anemia in DD-CKD patients as an alternative to ESAs."

Journal • Retrospective data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Enarodustat for the Treatment of Anemia in Chinese Patients with Non-Dialysis Chronic Kidney Disease: A Phase 3 Trial. (PubMed, Kidney Dis (Basel)) - "Its once-daily oral administration offers convenience that may enhance the adherence. Enarodustat shows the potential as a promising therapy for anemic patients with ND-CKD."

Journal • P3 data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

EPO-Mimetic Peptide Pegmolesatide Therapy for Pure Red Cell Aplasia in a Patient with Non-dialysis-dependent Type 1 Diabetic Nephropathy: A Case Report. (PubMed, Kidney Med) - "Enarodustat and roxadustat were administered successively after discontinuation of EPO, but anemia did not improve, and the patient was maintained with weekly blood transfusions. Subsequently, the EPO-mimetic peptide pegmolesatide was administered, and the patient's hemoglobin started to increase after 1 week and increased from 50 g/L to 92 g/L over approximately 3 months. Based on these findings, we speculate that pegmolesatide can provide a safe, effective, and convenient therapeutic strategy for PRCA in Chinese patients with chronic kidney disease."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hematological Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus

Bioanalysis, Analysis, Chemistry, and Pharmacological Aspects of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors. (PubMed, Curr Top Med Chem) - "The development of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIFPHIs), such as Roxadustat (ROX), Enarodustat (ENA), Desidustat (DES), Vadadustat (VAD), Molidustat (MOL), and Daprodustat (DAP), has significant effects on anemia in chronic kidney disease. Research indicates that most studies concentrate on hyphenated methodologies for drug estimation in various biological fluids. Consequently, this study assesses the biological efficacy of HIF-PHIs and elucidates the analytical methodologies currently employed for measurement across various matrices."

Journal • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

CANNON: Correction of Anemia with Enarodustat in Non-dialysis Dependent Chronic Kidney Disease (clinicaltrials.gov) - P4 | N=1670 | Not yet recruiting | Sponsor: Shanghai Zhongshan Hospital

New P4 trial • Anemia • Chronic Kidney Disease • Congestive Heart Failure • Hematological Disorders • Nephrology • Renal Disease

SAL-0951 in the Treatment of Chemotherapy-induced Anemia in Patients With Non-myeloid Malignancies (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.

New P2 trial • Anemia • Chemotherapy-Induced Anemia • Hematological Disorders • Oncology