Jesduvroq (daprodustat) / GSK, Kyowa Kirin - LARVOL DELTA

30 years of classical hematology drugs in the US: Approvals, costs, and sales (ASH 2025) - "Six drugs have been discontinued (year approved/year discontinued/reason): betrixaban(2017/2020/business), daprodustat (2023/2024/business), fidanacogene elaparvovec(2024/2025/business), oprelvekin (1997/2011/business), peginesatide (2012/2013/safety), and voxelotor(2019/2024/safety).There are limitations to our study. Some drugs have non-classical hematology indications (anticoagulantsin atrial fibrillation; luspatercept in myelodysplastic neoplasm) and/or may also be prescribed by non-classical hematologists (erythropoiesis stimulating agents by nephrologists and medical oncologists)...Classical hematology drugs contribute substantially to US prescription drug spending, with over $70billion in annual sales and medications for thromboembolism accounting for over half of the costs.Approvals have accelerated over the past three decades, doubling each decade. Biologics and biosimilarsnow represent two-thirds of approvals. Continuous-duration treatments, particularly for..."

Anemia • Atrial Fibrillation • Beta-Thalassemia • Cardiovascular • Chemotherapy-Induced Neutropenia • Chronic Kidney Disease • Complement-mediated Rare Disorders • Gene Therapies • Genetic Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hemophilia • Immune Thrombocytopenic Purpura • Immunology • Myelodysplastic Syndrome • Nephrology • Neutropenia • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease • Sickle Cell Disease • Thrombocytopenia • Thrombocytopenic Purpura

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

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

A computer-aided drug repurposing: the antibacterial agents targeting GroEL. (PubMed, Br J Pharmacol) - "This study validated our computational workflow for repurposing non-antibacterial drugs as antibacterial agents, demonstrating that cost-effective, computer-aided drug repurposing is a feasible strategy for identifying new therapeutic approaches to diseases, such as cancer, diabetes and COVID-19. Furthermore, the synergistic effect of daprodustat combined with an efflux pump inhibitor (e.g. PAβN) represents a promising therapeutic approach against both Gram-positive and Gram-negative bacterial pathogens."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Oncology

Daprodustat in heart failure and renal Anemia: Still early, but promising. (PubMed, J Cardiol) - No abstract available

Journal • Anemia • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Renal Disease

Daprodustat, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor, Improves Hematological Insufficiency without Progression of Myelodysplastic Syndrome with Chronic Kidney Disease (ASH 2023) - "ConclusionHIF-PHi administration did not lead to MDS progression. Notably, in MDS patients with CKD, low TSAT was a predictor for achieving HI by HIF-PHi."

Anemia • Bone Marrow Transplantation • Cardiovascular • Chronic Kidney Disease • Dermatology • Eosinophilia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Musculoskeletal Diseases • Myelodysplastic Syndrome • Myocardial Infarction • Nephrology • Oncology • Orthopedics • Pneumonia • Renal Disease • Respiratory Diseases • Solid Tumor • Transplantation • Wilms Tumor • HIF1A • WT1

Haematologic Effects of Long-Term Daprodustat in Patients on Maintenance Hemodialysis: A Three-Year Evaluation (KIDNEY WEEK 2025) - "Changes in MCV, MCH, and MCHC and a reduction in RDW-CV suggest favorable modulation of erythrocyte indices. Additionally, increased serum iron and TSAT without a rise in ferritin indicate enhanced iron utilization without iron overload."

Clinical • Hematological Disorders • 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

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in a Rat 5/6 Nephrectomy Model (ASH 2024) - "BackgroundTwo hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI), daprodustat and vadadustat, have been approved by FDA to treat dialysis dependent (DD) chronic kidney disease (CKD) anemia patients in US while all HIF-PHIs failed in getting approval by FDA in treating non-dialysis dependent (NDD) CKD anemia in US due to safety concerns. The hematocrits (%) for 5 groups were between 38.2±1.5 and 39.4±2.0 on day 1, were 41.6±1.6**, 36.3±1.9, 36.3±1.4, 37.2±1.2, and 36.3±1.7 respectively on day 35, were 41.8±1.3**, 36.8±2.4, 39.4±1.9*, 43.9±1.4**, and 51.4±2.8** respectively on day 49, and were 41.0±1.2**, 35.2±2.3, 39.0±3.6*, 45.7±3.1**, and 59.1±3.7** respectively on day 63. (Significance analysis was compared to group 2,* p<0.05,** p < 0.01)ConclusionThe rat 5/6 nephrectomy CKD anemia model was successfully established; on day 63, RBC, HGB, and HCT for rats in three..."

Preclinical • Anemia • Beta-Thalassemia • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease • MYC

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in Sprague Dawley Rats (ASH 2024) - "BackgroundInhibiting hypoxia-inducible factor prolyl hydroxylase (HIF-PH) by oral small molecules has been intensively pursued in treating chronic kidney disease (CKD) anemia during the past 20 years, leading to approval of daprodustat and vadadustat by FDA in treating dialysis-dependent (DD) CKD anemia in US while both plus roxadustat failed in getting approval by FDA in treating non-dialysis dependent (NDD) CKD anemia in US due to safety concerns. The hematocrits (%) for group 1 to 4 were between 38.7 and 39.1 on day 1, were 41.7±1.5, 44.0±2.0, 48.6±2.5**, and 57.9±2.7** respectively on day 28, and were 42.5±1.4, 41.7±1.5, 43.6±1.5, and 41.9±0.9 respectively on day 56. (Significance analysis was compared to group 1,* p<0.05,** p<0.01)ConclusionRBC, HGB, and HCT in normal SD male rats were significantly increased after dosing AND017 at 2.5 and 5 mg/kg PO QD for 4 weeks and gradually recovered to background levels after..."

Preclinical • Anemia • Beta-Thalassemia • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease • MYC

Daprodustat Induces Fetal Hemoglobin and Erythropoietic Drive in an in Vitro and In Vivo Model of Sickle Cell Disease (ASH 2024) - "The current standard of care therapy, hydroxyurea (HU), inhibits polymerization of abnormal hemoglobin S (HbS) by inducing fetal hemoglobin (HbF) expression, preventing vaso-occlusive complications...In addition, the HIF-PHI roxadustat (roxa) has been shown to induce HbF expression in CD34+ hematopoietic stem and progenitor cells (HPSCs) in vitro, suggesting multiple therapeutic benefits in SCD...Finally, we saw a decrease in all three cell lines (WBC, RBC, and platelets) in the vehicle group at D21, concerning for bone marrow toxicity from the vehicle, suggesting that the erythropoietic effect of dapro treatment may have been even greater without this confounding effect. In summary, daprodustat proves to be a promising candidate for treatment of anemia in SCD, and the long-term effects of daprodustat on erythropoiesis, HbF induction, and iron metabolism in SCD should be further evaluated."

Preclinical • Anemia • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease • CD34 • EPO • HIF1A

The cocrystal advantage: overcoming polymorph patent barriers in generic drug development. (PubMed, Mol Divers) - "Through case studies of recently developed cocrystals for APIs like Daprodustat, Roxadustat, and Vadadustat, we illustrate the practical application and commercial potential of this strategy. Ultimately, pharmaceutical cocrystals represent a critical convergence of materials science, regulatory law, and drug delivery, offering an innovative and effective route for accelerating patient access to affordable and improved medicines."

Journal • Review

Erythropoiesis-Stimulating Agents (ESAs) in Chronic Kidney Disease and Cancer-Related Anemia: A Narrative Review of Literature. (PubMed, Cureus) - "Anemia associated with chronic kidney disease (CKD) and cancer is conventionally managed with packed red blood cell (PRBC) transfusions or erythropoietin-stimulating agents (ESAs) like epoetin alfa; however, transfusions are limited by complications such as alloimmunization and infection risk, which has led to ESAs becoming the preferred standard of care...The emerging alternative of HIF-PHIs shows promise in mitigating these adverse risks with a similar treatment efficacy to ESAs. However, there is still a lack of long-term safety data on these treatment options, and future research should focus on determining this risk profile as well as potential dosing strategies to potentially guide the use of HIF-PHIs in future clinical practice as a novel therapeutic alternative for anemia of CKD and cancer-related anemia."

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

Model-Informed Drug Development for Daprodustat Supports the Design of Individualized Dosing Regimens in Chronic Kidney Disease Patients With Anemia. (PubMed, Clin Pharmacol Ther) - "This tutorial illustrates how integrated quantitative approaches, including longitudinal hemoglobin response modeling, population pharmacokinetics (PopPK), and clinical trial simulations, were applied to guide phase III dose selection, inform trial design, and support regulatory interactions. We highlight the evolution and application of these models, emphasizing key development decisions, challenges encountered, and insights gained."

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

Nardilysin in adipocyte regulates insulin sensitivity via HIF1α and PPARγ. (PubMed, Sci Rep) - "The augmented Akt phosphorylation by NRDC knockdown was reversed by daprodustat, which stabilizes HIF1α, suggesting that the effect of NRDC on insulin sensitivity is mediated by HIF1α...We also confirmed the complex formation of NRDC and PPARγ. In conclusion, NRDC in adipocyte regulates insulin sensitivity through HIF1α and PPARγ."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • HIF1A • PPARG

Structure-Based Optimization of HIF-2α Agonists That Synergistically Enhance Erythropoietin Production with PHD Inhibitors. (PubMed, J Med Chem) - "Notably, SD-10 exhibited remarkable synergy with Daprodustat, an approved PHD inhibitor, in stimulating erythropoietin (EPO) secretion both in cellular models and animal studies. These findings not only provide insights into HIF-2α activation mechanism, but also offer a promising lead compound for developing innovative treatments for renal anemia."

Journal • Hematological Disorders • Targeted Protein Degradation • EPAS1

Effects of Daprodustat on Iron Metabolism in Peritoneal Dialysis Patients: An Exploratory Study. (PubMed, Blood Purif) - "Methods This single-center, prospective study included 11 patients undergoing maintenance peritoneal dialysis who shifted from darbepoetin alfa to daprodustat. However, the absence of significant hemoglobin improvement, combined with the small sample size (n=11), lack of control group, and short 24-week follow-up period, significantly limits the clinical relevance and generalizability of these findings. Larger randomized controlled trials with longer follow-up periods are essential to definitively establish the efficacy and safety of daprodustat in this patient population."

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

Daprodustat for patients with heart failure and renal Anemia: A pilot multicenter, open-label, randomized controlled study. (PubMed, J Cardiol) - "Daprodustat effectively increases hemoglobin levels and modifies iron metabolism by decreasing hepcidin levels and increasing iron utilization in patients with HF and renal anemia."

Journal • Anemia • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Renal Disease

Characteristics and management of patients with renal anaemia treated with daprodustat: an observational study in Japan. (PubMed, Curr Med Res Opin) - "Approximately a third (DD) to almost half (ND) of patients with renal anaemia were not receiving treatment for anaemia. An increase in haemoglobin levels was observed after initiation of daprodustat, including in patients previously treated with erythropoiesis-stimulating agents, however causality cannot be confirmed due to lack of a control group."

Journal • Observational data • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

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

The Safety and Efficacy of Daprodustat for Recipients in Peritransplant Period: a Single-Center Retrospective Study on Post-Transplant Anemia Management in Kidney Transplantation. (PubMed, Transpl Int) - No abstract available

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

The efficacy of daprodustat compared to standard recombinant human erythropoietin (rhEPO) in treating anemia among patients undergoing dialysis: A systematic review and meta-analysis. (ASCO 2025) - "Daprodustat demonstrates non-inferiority to standard rhEPO therapy for the management of CKD-associated anemia in patients undergoing hemodialysis. Table 1. Pooled Effect Size for Change in Hemoglobin from Baseline."

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

Association of Different Definitions of Erythropoiesis-Stimulating Agent Hyporesponsiveness with Major Adverse Cardiovascular Events: Insights From ASCEND-D. (PubMed, Kidney360) - P3 | "Baseline ESA hyporesponsiveness is a potent predictor of MACE among patients receiving maintenance dialysis in ASCEND-D. All pre-specified definitions were similarly associated with a higher risk of MACE."

Adverse events • Journal • Cardiovascular • Myocardial Infarction

Anemia Studies in CKD: Erythropoiesis Via a Novel PHI Daprodustat - Pediatric (ASCEND-P) (clinicaltrials.gov) - P3 | N=4 | Completed | Sponsor: GlaxoSmithKline | Active, not recruiting ➔ Completed | N=75 ➔ 4 | Trial completion date: Jul 2030 ➔ Mar 2025 | Trial primary completion date: Jul 2030 ➔ Mar 2025

Enrollment change • Pan tumor • Trial completion • Trial completion date • Trial primary completion date • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Pediatrics • Renal Disease

Efficacy and safety of daprodustat versus darbepoetin alfa in the treatment of anemia in chronic renal failure: Systematic review and meta-analysis of randomized controlled trials. (PubMed, J Pharmacol Sci) - "DPD is not inferior to DBPA in the treatment of anemia in chronic renal failure."

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