Musredo (molidustat) / Bayer - LARVOL DELTA

Comparative effectiveness of darbepoetin vs other agents in chronic kidney disease-related anemia: a systematic review and network meta-analysis. (PubMed, BMC Nephrol) - "Daprodustat and roxadustat indicated equivalent or higher efficacy when compared to darbepoetin in elevating hemoglobin levels in CKD-related anemia, with daprodustat demonstrating a good safety profile. While conventional ESAs remain beneficial, HIF-PHIs offer promising oral alternatives with possible benefits in cardiovascular safety and decreased hypertension risk. Further head-to-head trials are necessary to confirm these findings and guide individualized treatment strategies."

Clinical • HEOR • Journal • Retrospective data • Review • Anemia • Cardiovascular • Chronic Kidney Disease • Diabetes • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

Darbepoetin vs. Other Agents in CKD Anemia: A Meta-Analysis (KIDNEY WEEK 2025) - "Results Molidustat showed the best cardiovascular and thrombotic safety despite lower efficacy, while methyl polyethylene glycol-epoetin beta showed the largest Hb increase in this network meta-analysis of 12 randomized trials involving over 4,000 CKD patients with anemia...Conclusion Daprodustat and roxadustat indicated equivalent or higher efficacy when compared to darbepoetin in elevating hemoglobin levels in CKD-related anemia, with daprodustat demonstrating a good safety profile...Comparitive efficacy of ESAs + Lower rank number = greater hgb-raising efficacy. * Comparison only, not an exact quantitative ranking."

Retrospective data • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hypertension • Nephrology • Renal Disease

Clinical therapeutics in feline medicine: updates for old and new drugs. (PubMed, J Feline Med Surg) - "The clinical use of these agents, available pharmacokinetic and pharmacodynamic data, and reported adverse effects in cats are presented. The information in this article is relevant to all veterinarians who practice feline medicine."

Journal • Review

Light-driven biosensor for the rapid and selective detection of hypoxia-inducible factor-prolyl hydroxylase domain inhibitors in aqueous media and saliva. (PubMed, Mikrochim Acta) - "HIF inhibitors such as Molidustat and Vadadustat are used as doping agents in racing sports. The new materials were also utilised for the rapid screening of HIF-PHI in spiked saliva samples. The new materials and light-driven surface functionalisation process can be easily adopted to develop new screening methods for multiple biomolecules (e.g. drugs, proteins, disease biomarkers, environmental toxins) for many applications (e.g. therapeutic drug monitoring, doping control, clinical diagnostics environmental monitoring)."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Discovery and characterization of a novel HIF-2α agonist for the treatment of CKD-related renal anemia. (PubMed, Acta Pharmacol Sin) - "In zebrafish (Danio rerio), AT-1 (10 or 50 μM) exhibited favorable safety profiles and, when combined with the prolyl hydroxylase (PHD) inhibitor Molidustat (10 μM), effectively mitigated doxorubicin-induced anemia. In adenine-induced chronic kidney disease (CKD) mouse model, combined administration of AT-1 (50 mg·kg-1·d-1, i.p.) and Molidustat (10 mg·kg-1·d-1, i.p.) for 15 days produced stronger effects on increasing EPO levels and alleviating anemia than Molidustat alone, further supporting the therapeutic potential of AT-1 in CKD-related anemia."

Journal • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • ARNT • EPAS1

In Vitro and Ex Vivo Evidences that Pharmacological Induction of the Hypoxia Response Pathway Efficiently Restricts Measles and Nipah Virus Infections. (PubMed, Emerg Microbes Infect) - "A similar antiviral effect was observed with Roxadustat and Daprodustat, two PHD enzyme inhibitors chemically unrelated to Molidustat. Finally, we showed that Molidustat inhibits NiV infection in organotypic cultures of hamster cerebellum and lung, thereby validating its effect in the two organs mainly targeted during infection. Taken together, our results provide evidence that pharmacological activation of the hypoxia-response pathway restricts MeV and NiV infections, highlighting HIF-inducing drugs as promising candidates to consider in the development of treatments."

Journal • Preclinical • CNS Disorders • Infectious Disease • Measles • Respiratory Diseases

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

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

A Study to Learn More About the Long-term Safety and Effectiveness of Molidustat as a Treatment for Japanese Men and Women With Renal Anemia (clinicaltrials.gov) - P=N/A | N=1081 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Hematological Disorders

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors as a New Treatment Option for Anemia in Chronic Kidney Disease. (PubMed, Biomedicines) - "Clinical studies have shown that the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) covered in this manuscript-roxadustat, vadadustat, daprodustat, and molidustat-effectively increase hemoglobin (Hb) levels in both non-dialyzed and dialyzed CKD patients. and retinopathy. More extensive and long-term clinical trials of HIF-PHIs-based anemia treatment in CKD patients are needed, and their results will indicate whether HIF-PHIs represent an effective and safe alternative to EPO and iron supplementation for anemia treatment in CKD patients."

Journal • Review • Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Oncology • Renal Disease • Retinal Disorders

Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress. (PubMed, Cell Mol Life Sci) - "This was accompanied by a higher resistance to the inhibition of mitochondrial respiration by antimycin A, a phenotype confirmed in Roxadustat-treated Huh7 cells and Molidustat-treated hepatoblastoma cells (Huh6 and HepG2). Overall, this study shows that HIF-inducing drugs increase the metabolic resilience of liver cancer cells to metabolic stressors, arguing for careful monitoring of patients treated with HIF-inducing drugs, especially when they are at risk of liver cancer."

Journal • Gastrointestinal Cancer • Hematological Disorders • Hepatoblastoma • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • EPAS1 • HIF1A • LDHA • SERPINE1

Simultaneous detection of three hypoxia-inducible factor stabilizers-molidustat, roxadustat, and vadadustat-in multiple keratinized matrices and its application in a doping context. (PubMed, Drug Test Anal) - "Limits of quantification were 2, 0.5, and 5 pg/mg for molidustat, roxadustat, and vadadustat, respectively. The analysis of the athlete's head hair (collected 1 month after the urine test) showed a concentration of molidustat of 135 pg/mg, and his beard hair and his fingernails clippings contained 55 and 40 pg/mg, respectively."

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

A Prospective Randomized Controlled Clinical Study to Investigate the Efficacy and Safety of Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitors in Non-Dialysis Patients with Chronic Heart Failure and Renal Anemia Switched from Continuous Erythropoietin Receptor Activator Treatment. (PubMed, J Clin Med) - " Forty patients were randomized by the envelop method to receive treatment with roxadustat, daprodustat, vadadustat, or molidustat. The individual HIF-PH inhibitors appear to have different effects on anemia and thyroid function. However, because this was a single-center study with a limited sample size, the efficacy and potential limitations of HIF-PH inhibitors need to be further clarified."

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

The comparison of four hypoxia-inducible factor prolyl hydroxylase inhibitors on drug potency and cost for treatment in patients with renal anemia. (PubMed, Clin Exp Nephrol) - "The difference in dose escalation for anemia treatment among HIF-PHIs is due to differences in drug potency, where the HPI significantly differs among HIF-PHIs. The disparity between the HPI and the cost of the initial dose accounts for the variance in the daily costs of renal anemia treatment among HIF-PHIs."

Journal • Anemia • Hematological Disorders

The efficacy and safety of molidustat for anemia in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A systematic review and meta-analysis. (PubMed, Heliyon) - "There was no significant difference in the incidence of severe adverse events (SAEs), death, and cardio-related adverse events between molidustat and the ESAs groups. Moricizine can effectively improves Hb levels in NDD patients and corrects anemia in DD patients without increasing adverse event incidence."

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

The drug-specific properties of hypoxia-inducible factor-prolyl hydroxylase inhibitors in mice reveal a significant contribution of the kidney compared to the liver to erythropoietin induction. (PubMed, Life Sci) - "Renal EPO induction is the major target of HIF-PH inhibitors for their therapeutic effects on erythropoiesis. Additionally, the drug-specific properties of HIF-PH inhibitors in EPO induction and iron metabolism have been shown in mice, providing useful information for selecting the proper HIF-PH inhibitor for each renal anemia patient."

Journal • Preclinical • Hematological Disorders • Nephrology • Renal Disease • EPO • ERFE

Low molecular weight acids and OATP1B mediated hepatic clearance: In vitro and in vivo evaluation using novel hypoxia-inducible factor prolyl hydroxylase inhibitors (Dustats). (PubMed, Drug Metab Dispos) - "Five acid dustats, namely daprodustat, desidustat, enarodustat, roxadustat and vadadustat, showed specific transport by OATP1B1/1B3 in transporter-transfected HEK293 cells...Hepatic clearance (non-renal) was about 4-fold (vadadustat) to >11-fod (daprodustat and roxadustat) higher in control group compared to rifampin-treated subjects...Significant active uptake mechanisms are not apparent for the neutral compound, molidustat. Characterization of uptake mechanisms is therefore important in predicting human pharmacokinetics and evaluating drug-drug interactions for low MW acids."

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

New Therapeutic Strategies in the Treatment of CKD Anemia: Hypoxia-Induced Factor Prolyl-Hydroxylase Inhibitors (PubMed, G Ital Nefrol) - "The drugs currently produced are roxadustat, daprodustat, vadadustat, molidustat, desidustat, and enarodustat; among these only roxadustat is currently approved and usable in Italy. The possibility of oral intake, pleiotropic activity on martial and lipidic metabolism, and the non-inferiority compared to erythropoietins make these drugs a valid alternative to the treatment of anemia associated with chronic kidney disease in the nephrologist practice."

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

Use of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, in chronic kidney disease-associated anemia in cats. (PubMed, J Vet Intern Med) - "Daily PO molidustat administration may stimulate a clinically relevant erythropoietic response in anemic cats with CKD. This HIF-PH inhibitor may be an alternative for managing anemia in cats compared to recombinant EPO treatment."

Journal • Anemia • Hematological Disorders • Nephrology • Renal Disease

CHARACTERISTICS OF PATIENTS WITH CKD WHO USE HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITORS: A JAPAN MEDICAL DATA CENTER DATABASE STUDY (ERA-EDTA 2023) - "Available HIF-PHIs include roxadustat (approved Sept 2019), daprodustat (approved June 2020), vadadustat (approved June 2020), enarodustat (approved Sept 2020) and molidustat (approved Jan 2021). Evaluating a real-world database for patients initiating HIF-PHIs within Japan allows for a more comprehensive picture of patient clinical and demographic characteristics. Our analysis found most patients initiating on HIF-PHIs were male, had previous rhEPO use, and had history of hypertension and diabetes. Understanding patient profiles in a real-world setting may guide treatment decisions in clinical practice."

Clinical • Anemia • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology

HIFS AND BUTS : A NETWORK META-ANALYSIS OF HIF-PH INHIBITORS & ESAS IN NDD-CKD PATIENTS WITH ANEMIA COMPARING THEIR SAFETY AND EFFICACY (ERA-EDTA 2023) - "Compared to ESA, all HIF PHIs increased risk for SAEs (daprodustat of RR, 1.21[95% CI, 0.825–1.77]; desidustat, 1.38[95% CI, 0.695–2.76]; enarodustat, 1.29[95% CI, 0.568–3.02]; molidustat, 1.02[95% CI, 0.585–1.74]; roxadustat, 1.29[95% CI, 0.674–2.57] and vadadustat, 1.01[95% CI, 0.693–1.47]) although these differences were statistically non-significant. In terms of safety, HIF PHIs were associated with more SAEs compared to ESA although these differences are not statistically significant. Comparing efficacy, HIF-PHIs and ESA both effectively increase Hb level in NDD-CKD patients without any significant difference. Results of our network meta-analysis suggest the need for larger and long-term studies comparing HIF-PHIs with ESAs to have better understanding of their comparative efficacy and safety profiles."

Retrospective data • Anemia • Chronic Kidney Disease • Hematological Disorders

Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis. (PubMed, Front Pharmacol) - "The occurrence of gastrointestinal disorder was higher in enarodustat and roxadustat than in ESAs (RR: 6.92, 95% CI: 1.52-31.40, p = 0.01; RR: 1.30, 95% CI: 1.04-1.61, p = 0.02)...The occurrence of vascular-access complications was higher in roxadustat (RR: 1.15, 95% CI: 1.04-1.27, p<0.01) and lower in daprodustat (RR: 0.78, 95% CI: 0.66-0.92, p<0.01) than in ESAs...For hemoglobin response, network meta-analysis showed that compared with ESAs, significant increases were shown in roxadustat (RR: 1.04, 95% CI: 1.01-1.07, p<0.01) and desidustat (RR: 1.22, 95% CI: 1.01-1.48, p = 0.04), whereas noticeable reductions were indicated in vadadustat (RR: 0.88, 95% CI: 0.82-0.94, p<0.01) and molidustat (RR: 0.83, 95% CI: 0.70-0.98, p = 0.02)... Although HIF-PHIs did not show significant differences from ESAs in terms of overall AEs and SAEs, statistical differences in gastrointestinal disorder, hypertension, and vascular-access complications were observed between..."

Retrospective data • Review • Anemia • Cardiovascular • Chronic Kidney Disease • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Nephrology • Renal Disease

Treatment satisfaction with molidustat in CKD-related anemia in non-dialysis patients: a post-hoc analysis of two clinical trials. (PubMed, Clin Exp Nephrol) - P3 | "These patient-reported satisfaction outcomes support the use of molidustat as a patient-centered treatment option for CKD-related anemia."

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

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease. (PubMed, Aging (Albany NY)) - "The most effective treatment for hemoglobin correction is roxadustat. The superior efficacy of reducing hepcidin makes roxadustat and enarodustat appropriate for patients with inflammation. However, the increased risk of hypertension and thrombosis associated with roxadustat should be noted. In patients at risk for hypertension and thrombosis, molidustat and ESAs may be preferable options. When administering roxadustat and daprodustat, clinicians should check ferritin to assess iron storage. Lower TSAT in patients receiving HIF-PHIs and ESAs treatment suggests intravenous iron supplements are needed."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hypertension • Inflammation • Nephrology • Renal Disease • Thrombosis