Evrenzo (roxadustat) / Astellas, AstraZeneca, Kyntra Bio - LARVOL DELTA

Pharmacological HIF activation protects against diet-induced obesity, glucose intolerance, and skeletal dysfunction by exerting dual beneficial effects on energy metabolism and bone. (PubMed, Bone Res) - "Specifically, short-term FG-4592 treatment during fracture recovery reduced the body weight and fat mass of obese mice, improved glucose tolerance, and enhanced the fracture bridging capacity, along with promoting callus vascularization. These findings demonstrate that systemic hypoxia signaling stimulation using PHD inhibitors alleviates both the metabolic and skeletal consequences of diet-induced obesity in mice, highlighting its potential as a dual-action therapeutic strategy for enhancing glucose homeostasis and bone health/regeneration in disorders of obesity and metabolic dysfunction."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Obesity • Orthopedics • Type 2 Diabetes Mellitus

Efficacy and safety of prolyl hydroxylase inhibitors for anemia in chronic kidney disease: a network meta-analysis. (PubMed, Ren Fail) - "Roxadustat improved serum iron in D-CKD (MD = 6.19 μg/dL, 95% CI: 2.81-9.58), and vadadustat and roxadustat reduced hepcidin in ND-CKD. Regarding safety, ESA had the lowest AE risk in ND-CKD (OR = 0.85, 95% CI: 0.74-0.98), while roxadustat ranked lowest (SUCRA = 18.4%). Roxadustat demonstrated the strongest efficacy in hemoglobin improvement but higher AE incidence in ND-CKD, whereas ESA and daprodustat showed safety and iron metabolism benefits, supporting individualized therapy for renal anemia.Registration number: PROSPERO (CRD420251066181)."

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

A Rising Cluster of Erythropoietin-Associated Pure Red Cell Aplasia and Subsequent Response to Roxadustat: A Case Series. (PubMed, Nephrology (Carlton)) - "We describe 14 cases of Epoetin-alfa associated PRCA which have resulted in significant morbidity...Heterogeneous immunosuppression regimens were used, predominantly with either monotherapy prednisone or ciclosporin...Our cluster of cases highlights the need for strong suspicion of acquired PRCA in patients treated with erythropoietin products who present with refractory anaemia. HIF stabilisers such as Roxadustat, which have otherwise not been licensed in New Zealand, seem to be beneficial in these cases, possibly minimising the need for heavy immunosuppression."

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

Roxadustat for Refractory Anemia Associated to Cytomegalovirus Infection in Kidney Transplantation. (PubMed, Transplant Proc) - "Case 1: A 72-year-old woman developed anemia (Hb 8 g/dL) during asymptomatic CMV viremia despite valganciclovir, everolimus switch, and escalating ESA doses (up to 18,000 IU/wk). These cases support roxadustat as a valuable option in managing post-KT anemia with CMV-associated ESA resistance, by stimulating endogenous EPO, reducing hepcidin, and improving iron utilization. Further prospective studies are needed to establish its safety and efficacy in this population."

Journal • Anemia • Cytomegalovirus Infection • Hematological Disorders • Infectious Disease • Inflammation • Transplantation • EPAS1

Effect of HIF-PHI on anemia in patients with chronic kidney disease and its influence on vascular calcification (ChiCTR) - P=N/A | N=50 | Completed | Sponsor: The First Affiliated Hospital of Anhui University of Science and Technology; The First Affiliated Hospital of Anhui University of Science and Technolo

New trial • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • FGF23

Mechanistic Evaluation of Roxadustat for Pulmonary Fibrosis: Integrating Network Pharmacology, Transcriptomics, and Experimental Validation. (PubMed, Pharmaceuticals (Basel)) - " These data indicate that roxadustat ameliorates bleomycin-induced PF in mice, an effect associated with modulation of the NF-κB and PPAR signaling pathways. The findings provide a preclinical rationale for further investigation of roxadustat as a potential treatment for PF."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • IL1B • NFKBIA • PPARG • S100A8 • S100A9 • TGFB1 • TNFA

Frequency-reduction strategy of roxadustat in patients undergoing peritoneal dialysis: a multi-center retrospective cohort study. (PubMed, Front Med (Lausanne)) - "Compared to the dose-reduction group, the frequency-reduction group showed higher hemoglobin target attainment rates, lower hemoglobin variability, and a reduced risk of hemoglobin target non-attainment. The frequency-reduction strategy appears to be a potential tapering approach for peritoneal dialysis (PD) patients."

Journal • Retrospective data

Sex-Specific Impact of Roxadustat on Residual Kidney Function in Peritoneal Dialysis Patients: A Propensity Score-Weighted Analysis. (PubMed, Kidney Med) - "Roxadustat delays RKF decline in male CAPD patients while providing comparable anemia control and favorable lipid profile effects as ESAs. These sex-specific outcomes suggest underlying biological mechanisms, highlighting the need for larger, targeted studies to further elucidate the potential benefits of roxadustat in this population."

Journal • Dyslipidemia • Hematological Disorders

MgFe-LDH nanocomposites incorporated into gelatin methacryloyl /hyaluronic acid methacrylated hydrogels for controlled drug release: Synergistic regulation of angiogenesis-osteogenesis for bone regeneration. (PubMed, Int J Biol Macromol) - "In this study, we developed an injectable smart hydrogel system (GH-LR) by incorporating roxadustat (RD)-loaded MgFe-layered double hydroxide nanoparticles into a gelatin methacryloyl/hyaluronic acid methacrylate (GH) hybrid matrix...The therapeutic effects stem from the synergistic interplay between locally sustained angiogenesis and osteogenesis induction. This biocompatible GH-LR system collectively represents an innovative approach for reconstructing large bone defects through controlled delivery and spatiotemporal coordination of pro-regenerative cues."

Journal • RUNX2

Roxadustat for renal anemia: current clinical experience. (PubMed, Front Pharmacol) - "In this review, we synthesize clinical insights from these novel therapeutics and highlight some of the outstanding questions relevant to their clinical use. This study may provide theoretical framework and practical evidence for the clinical application of other HIF-PHIs."

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

Exploring the potential application of roxadustat in chronic kidney disease-related osteoporosis based on the regulatory role of HIF-1α in bone metabolism. (PubMed, Histol Histopathol) - "The aim is to provide a robust theoretical foundation for exploring the potential therapeutic application of roxadustat to improve bone metabolism in patients with Chronic Kidney Disease-related Osteoporosis (CKD-RO). It is important to note that, while this review highlights promising findings, the current evidence is primarily derived from preclinical animal studies and necessitates rigorous clinical validation."

Journal • Review • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Osteoporosis • Renal Disease • Rheumatology • HIF1A

Open-label, Phase 2 study of roxadustat for the treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies. (PubMed, Am J Hematol) - "Roxadustat increased Hb in patients with CIA regardless of tumor type and chemotherapy regimen. Adverse events were consistent with observations in patients with advanced-stage malignancies."

Journal • P2 data • Anemia • Cardiovascular • Chemotherapy-Induced Anemia • Hematological Disorders • Hematological Malignancies • Oncology • Pulmonary Embolism • Respiratory Diseases • Venous Thromboembolism

Efficacy and Safety of Roxadustat for Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndrome (LR-MDS) with Low Red Blood Cell (RBC) Transfusion Burden: Results of Phase III Matterhorn Study (ASH 2023) - P3 | "Despite not meeting the primary endpoint, roxadustat plus BSC was well-tolerated, and a high percentage of pts with LR-MDS and LTB were TI responders. The high TI response rate in the PBO arm, historically poor outcomes in pts with ESA-refractory disease, and the inclusion of pts who were not transfusion-dependent (1 pRBC unit Q8W) may have contributed to the lack of a statistically significant difference in TI response rates between arms. MATTERHORN outcomes highlight the continued unmet need for effective and safe therapies that reduce RBC transfusion burden in LR-MDS."

Clinical • P3 data • Acute Myelogenous Leukemia • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Infectious Disease • Ischemic stroke • Leukemia • Myelodysplastic Syndrome • Myocardial Infarction • Nephrology • Oncology • Pneumonia • Renal Disease • Respiratory Diseases

Efficacy and Safety of Roxadustat for Anemia in Patients Receiving Chemotherapy for Nonmyeloid Malignancies: A Randomized, Open-Label, Active-Controlled Phase III Study. (PubMed, J Clin Oncol) - "Roxadustat was noninferior to rHuEPO-α in treating CIA in participants with nonmyeloid malignancies receiving multicycle treatments of myelosuppressive chemotherapy. The oral formulation of roxadustat may potentially increase compliance."

Journal • P3 data • Anemia • Chemotherapy-Induced Anemia • Hematological Disorders • Oncology

Cellular microenvironment of erythropoietin-producing cells in hypoxic and injured mouse kidneys. (PubMed, Exp Physiol) - "The REP cell microenvironment switched from pathways involved in energy metabolism in hypoxic conditions to inflammatory and fibrotic pathways in injury conditions. In summary, these data demonstrate that in the diseased kidney HIF stabilizers reinduce Epo expression in REP cells with a metabolically inactive proximal tubule neighbourhood, consistent with a causal role for tubular cells during the loss of Epo expression."

Journal • Preclinical • Fibrosis • Nephrology • Renal Disease • EPO

Safety Profile of Roxadustat in Anemic Patients: A Meta-Analysis of 21 RCTs. (PubMed, Medeni Med J) - "TEAEs leading to death were similar to ESA but higher than with placebo, whereas all-cause mortality was lower than with placebo and comparable to ESA. Taken together, current evidence supports the overall non-inferiority of roxadustat to ESA in terms of safety."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hypertension • Infectious Disease • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases

NANLING: Roxadustat Effectiveness/Safety in Chronic Kidney Disease-Associated Anemia with Peritoneal Dialysis. (PubMed, Kidney Dis (Basel)) - "Roxadustat corrected anemia in Chinese patients with CKD on PD, irrespective of baseline T2DM. Adverse events were consistent with roxadustat's known safety profile and with PD patients' characteristics."

Journal • Anemia • Chronic Kidney Disease • Diabetes • Hematological Disorders • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Type 2 Diabetes Mellitus

Effect of Roxadustat on bone metabolism markers in patients with renal anemia. (PubMed, Endocrine) - No abstract available

Journal • Anemia • Hematological Disorders • Metabolic Disorders

Roxadustat: A catalyst for diabetic wound healing through re-epithelialization and angiogenesis. (PubMed, Cytojournal) - "Roxadustat also reversed the downregulated expression of vascular endothelial growth factor and CD31 in diabetic mice (P < 0.05) and accelerated the wound angiogenesis process. Roxadustat shows potential as a therapeutic drug by promoting re-epithelialization and angiogenesis to bring vigor to the impaired diabetic wound."

Journal • Diabetes • Metabolic Disorders • CD31 • HIF1A • NICD • NOTCH1 • PCNA • PECAM1

Roxadustat induces erythroid differentiation of erythroleukemia cells through the hypoxia inducible factor-α / GATA binding protein 1 axis. (PubMed, Cell Signal) - "Roxadustat induces erythropoiesis in erythroleukemia primarily by targeting HIF-2α and was partially GATA1-dependent. Besides upregulating erythropoietin, our study revealed the HIF-α/GATA1 axis as another critical regulatory mechanism for hypoxia-driven erythropoiesis."

Journal • Acute Myelogenous Leukemia • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Leukemia • Nephrology • Oncology • Renal Disease • EPAS1 • GATA1 • HIF1A

Switchable Access to Quinolines and Isoquinolines via the Diverse Behavior of Transient Directing Groups. (PubMed, Org Lett) - "Its utility is demonstrated by a significantly streamlined three-step synthesis (formerly nine) of the antianemic drug roxadustat. This work establishes HOSA as a powerful catalytic transient directing group for selective C-H annulation, offering a new paradigm for heterocycle synthesis."

Journal

Effect of Roxadustat on Heart Failure Patients With Anaemia and Moderate-to-Severe Chronic Kidney Disease (clinicaltrials.gov) - P=N/A | N=200 | Not yet recruiting | Sponsor: Zhongda Hospital

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

Hypoxia-driven complement activation expands circulating endothelial cells in transplant-associated thrombotic microangiopathy: A multi-omics single-cell and functional study (ASH 2025) - "Both siHIF1A and eculizumab halved C3b loading and restored barrier integrity; roxadustat (HIF-PHD inhibitor) phenocopied hypoxia-induced complement activation. Conclusions Hypoxia activates complement and fuels CEC expansion in TA-TMA, linking two key pathogenic drivers.CEC percentage and a hypoxia transcriptomic score emerge as non-invasive early biomarkers, whilecombined hypoxia- and complement-targeted interventions warrant clinical testing to improve allograftoutcomes."

Transplantation • CD31 • HIF1A • KDR • MCAM • PECAM1 • PTPRC

FDA approval of imetelstat: a new era in the treatment of lower-risk myelodysplastic syndrome. (PubMed, Ann Med Surg (Lond)) - "Previously available treatments-including erythropoiesis-stimulating agents, lenalidomide, luspatercept, roxadustat, and azacitidine-have demonstrated variable efficacy and tolerability, with limited impact on long-term disease progression. Its approval underscores the importance of targeting fundamental disease mechanisms rather than merely alleviating symptoms. As additional data emerge from real-world settings and ongoing trials, Imetelstat may further reshape therapeutic algorithms and improve both quality of life and survival outcomes in this patient population."

FDA event • Journal • Review • CNS Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Psychiatry

The effect of SGLT2 inhibitor and HIF-PHI on the podocyte-specific molecules and cytoskeleton of diabetic podocytes. (PubMed, BMC Nephrol) - "SGLT2i Dapagliflozin and HIF-PHI Roxadustat partly restore the podocyte morphology and intracellular mRNA and protein levels of podocyte-associated molecule in a diabetic milieu."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease • NPHS1 • PODXL