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

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) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Retrospective data • Review • Anemia • Hematological Disorders

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

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

Drug-associated pancreatic cancer: insights from real-world pharmacovigilance and network pharmacology. (PubMed, Expert Opin Drug Saf) - "Except 4 antineoplastic agents, only 24 drugs indicated pancreatic cancer signals in 33,948 reports including 4 dipeptidyl peptidase-4 (DPP-4) inhibitors, 3 glucagon-like peptide-1 (GLP-1) analogues, 5 compound hypoglycemic agents, 3 hypotensive agents, ranitidine, pancrelipase, fondaparinux, naldemedine, daprodustat, megestrol acetate, leuprorelin, lecanemab, and lorcaserin. GLP1R (glucagon-like peptide 1 receptor) for GLP-1analogues, and PTEN (phosphatase and tensin homolog) for metformin might be a potential cause of pancreatic cancer. Clinicians providing these therapies should stay vigilant to detect pancreatic cancer early."

Adverse events • Journal • Real-world evidence • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • PTEN

Daprodustat: a new approach to the treatment of anemia in chronic kidney disease. (PubMed, Ceska Slov Farm) - "These drugs interfere with the regulation of erythropoietin, which is a key factor in the production of red blood cells. This drug was approved in Japan in June 2020 and clinical studies with it are ongoing in several countries around the world, where they focus on evaluating the effectiveness and safety in various populations of patients with chronic kidney disease."

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

Vadadustat (Vafseo) for anemia of chronic kidney disease. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Integrated Longitudinal Population Dose-Hemoglobin Response of Daprodustat Following Dose Titration in Patients With Anemia in Chronic Kidney Disease. (PubMed, Clin Pharmacol Ther) - "Titration-based visual predictive checks for Hgb target criteria for the analysis dataset and the prediction dataset showed that the model adequately predicted the observed data. This re-calibrated Dose-Hgb model will provide further support for the individualized dosing strategy in CKD patients with anemia treated with daprodustat."

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

Efficacy and safety of daprodustat in patients on peritoneal dialysis in the ASCEND-D trial. (PubMed, Nephrol Dial Transplant) - P3 | "This subgroup analysis of the ASCEND-D trial demonstrated comparable efficacy and safety of daprodustat versus darbepoetin alfa in PD patients, supporting its use in the treatment of anemia in these patients."

Journal • Cardiovascular • 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

Nanoscale Systems for Local Activation of Hypoxia-Inducible Factor-1 Alpha: A New Approach in Diabetic Wound Management. (PubMed, Int J Nanomedicine) - "Researchers have extensively explored HIF-1α activation as a potential pathway for diabetic wound management, focusing mainly on deferoxamine (DFO) as a potent agent to stabilize HIF-1α. This review provides an update of the other recent pharmacological agents managing HIF-1α activation, including novel PHD inhibitors (roxadustat and daprodustat) and Von Hippel-Lindau protein (VHL) antagonists, which could be potential alternatives for the local treatment of diabetic wounds...Given that, these novel drugs have minimal applications in diabetic wound healing, particularly in the context of local application through nanomaterials. This gap presents an exciting opportunity for further investigation, as combining these drugs with localized nanotechnology could avoid undesired systemic side effects and sustain drug release within wound site, offering a transformative platform for diabetes wound treatment."

Journal • Review • Diabetes • Metabolic Disorders • Von Hippel-Lindau Syndrome • HIF1A

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 • Pain • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease • CD34 • EPO • HIF1A

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

Successful treatment of low-risk myelodysplastic syndrome-related anemia in patients with chronic kidney disease with daprodustat: A report of two cases. (PubMed, EJHaem) - "Yet, their efficacy and safety against low-risk MDS are unclear. Here, we report two cases of low-risk MDS complicated with chronic kidney disease whose anemia responded to daprodustat treatment."

Journal • Anemia • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Nephrology • Oncology • Renal Disease

Hypoxia-inducible factor activators: a novel class of oral drugs for the treatment of anemia of chronic kidney disease. (PubMed, Hematology Am Soc Hematol Educ Program) - "Due to cardiovascular safety concerns, only 2 HIF-PHIs, daprodustat and vadadustat, have been approved for marketing in the United States, and only for patients on maintenance dialysis. We discuss unwanted on-target and off-target effects, review cardiovascular and other safety concerns, and provide a benefit/risk-based perspective on how this new class of oral drugs might impact current anemia management in CKD. A clinical case is presented that highlights the clinical complexities and therapeutic challenges in managing anemia in CKD."

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

Pharmacovigilance Analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Events for Daprodustat (KIDNEY WEEK 2024) - "FAERS analysis has highlighted anemia, acute exacerbation of heart failure, and venous thromboembolism as noteworthy adverse effects associated with daprodustat. Given its status as a novel medication, it is imperative to conduct further research and implement vigilant monitoring whilst on treatment with daprodustat. FAERS Adverse event proflie amongst hospitalizations (severe cases)"

Adverse events • Anemia • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hematological Disorders • Myocardial Infarction • Nephrology • Renal Disease • Venous Thromboembolism

Renoprotective Effects of Daprodustat in Patients with Chronic Kidney Disease and Renal Anemia. (PubMed, Int J Mol Sci) - "We reported the renoprotective effects of endogenous erythropoietin production on renal function in ischemic reperfusion injury (IRI) of the kidney using the prolyl hydroxylase domain (PHD) inhibitor, Roxadustat. The renoprotective effect of daprodustat was small in patients with serum creatinine larger than 3-4 mg/dL because of low residual renal function. The appearance of renal anemia would be a sign of the time to start using daprodustat."

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

Integrated Population Pharmacokinetics of Daprodustat in Patients with Chronic Kidney Disease with Anemia. (PubMed, Clin Pharmacokinet) - "The PopPK of daprodustat in the CKD population with anemia was adequately characterized. Allometrically-scaled body weight on clearance and volume, dialysis status on absorption and clopidogrel on clearance were statistically significant covariates."

Journal • PK/PD data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

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

Activation of PERK/eIF2α/ATF4/CHOP branch of endoplasmic reticulum stress response and cooperation between HIF-1α and ATF4 promotes Daprodustat-induced vascular calcification. (PubMed, Front Pharmacol) - " We concluded that DPD induces ER stress in vitro and in vivo, in which ATF4 serves as a downstream effector of HIF-1 activation. Targeting ATF4 could be a potential therapeutic approach to attenuate the pro-calcific effect of DPD."

Journal • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • ATF4 • BMP2 • HIF1A • HSPA5 • RUNX2 • SLC2A1 • SOX9 • TCF4

Hypoxia-inducible factor-prolyl hydroxylase inhibitors for treatment of anemia in chronic kidney disease: a systematic review and network meta-analysis. (PubMed, Front Pharmacol) - "Roxadustat and daprodustat had the largest number of reports in terms of adverse events. HIF-PHIs can effectively elevate hemoglobin without causing higher risk of safety concerns in CKD patients with anemia. Further evidence from long-term studies and the ongoing post-market surveillance is necessary."

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

Daprodustat reduces skeletal muscle ischemia-reperfusion injury in mice. (PubMed, J Orthop Surg (Hong Kong)) - "These data demonstrated that Daprodustat may provide a potential clinical approach for preventing or treating skeletal muscle injury induced by I/R."

Journal • Preclinical • Cardiovascular • Inflammation • Reperfusion Injury

Comparative Analysis of Real-World Efficacy and Safety of Hypoxia-Inducible Factor Prolyl-Hydroxylase Inhibitors in Kidney Transplant Recipients Versus Nontransplant Individuals: A Single-Center Study. (PubMed, Transplant Proc) - "HIF-PHis demonstrate comparable efficacy for managing anemia in CKD, regardless of transplant status. However, heightened vigilance for thrombosis events is necessary during follow-up for KTRs."

Journal • Real-world • Real-world effectiveness • Real-world evidence • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease • Thrombosis • Transplantation