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

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

Cerebral Infarction After Switching From Roxadustat to Daprodustat in a Patient With Renal Anemia. (PubMed, Cureus) - "It is unclear if the change to daprodustat was involved in the onset of cerebral infarction. However, this case suggests that particular caution should be paid to unexpected acute elevation of Hb after a change from one HIF-PH inhibitor to another, especially in a patient at high risk for cardiovascular events."

Journal • Anemia • Cardiovascular • CNS Disorders • Diabetes • Diabetic Nephropathy • Dyslipidemia • Endocrine Disorders • Fatigue • Hematological Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Transforming the management of chronic kidney disease-associated anemia using daprodustat. (PubMed, Ann Med Surg (Lond)) - No abstract available

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

Anemia Studies in CKD: Erythropoiesis Via a Novel PHI Daprodustat - Pediatric (ASCEND-P) (clinicaltrials.gov) - P3 | N=75 | Active, not recruiting | Sponsor: GlaxoSmithKline | Recruiting ➔ Active, not recruiting | N=120 ➔ 75

Enrollment change • Enrollment closed • Pan tumor • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Pediatrics • Renal Disease

DAPRODUSTAT IMPROVES ANEMIA IN A MOUSE MODEL OF SICKLE CELL DISEASE (EHA 2024) - "Hydroxyurea, the currentstandard-of-care treatment, increases fetal hemoglobin (HbF) expression, inhibiting HbS polymerization. Our study demonstrates that treatment with daprodustat can improve anemia in a mouse model of SCD. Furthermore, prolyl hydroxylase inhibition may reduce HbS polymerization by decreasing MCHC and increasingHbF expression, offering multiple therapeutic mechanisms for SCD. Thus, the effects of daprodustat onerythropoiesis, iron homeostasis, and HbS polymerization should be further evaluated in SCD."

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

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

Efficacy of daprodustat for patients on dialysis with anemia: systematic review and network meta-analysis. (PubMed, Pan Afr Med J) - "Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat."

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

ROQ-IT: A Prospective Interventional Study Assessing the Clinical and Operational Effectiveness of Transitioning From Mircera to Daprodustat for the Treatment of Anemia in End Stage Kidney Disease (clinicaltrials.gov) - P4 | N=161 | Completed | Sponsor: USRC Kidney Research | Active, not recruiting ➔ Completed | Trial completion date: Nov 2023 ➔ Feb 2024 | Trial primary completion date: Nov 2023 ➔ Feb 2024

Trial completion • Trial completion date • Trial primary completion date • Anemia • Chronic Kidney Disease • 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

Daprodustat (dapro) dosing among prespecified subgroups including erythropoiesis-stimulating agent hyporesponders (ESA-HR) in dialysis-dependent patients (pts) in the ASCEND program (NKF-SCM 2024) - P3 | "ESA-HR was associated with a higher assigned dose of dapro and ESA at Wk 52. Use of dapro in ESA-HR pts suggests similar dose adjustment considerations (number and % pts with dose adjustments) vs non-ESA-HR pts. In contrast, ESA-HR pts treated with ESAs may have different dose adjustment considerations vs non-ESA-HR pts."

Clinical • Anemia • Hematological Disorders

Outcome differences by race and ethnicity with daprodustat: insights from the ASCEND-D study (NKF-SCM 2024) - P3 | "Efficacy and CV safety of daprodustat were generally consistent across race and ethnicity subgroups in the ASCEND-D study."

Anemia • Cardiovascular • Chronic Kidney Disease • Hematological Disorders

Consensus commentary and position of the Italian Society of Nephrology on KDIGO controversies conference on novel anemia therapies in chronic kidney disease. (PubMed, J Nephrol) - "This class of drugs stimulates endogenous erythropoietin production and, at the same time, improves iron absorption and mobilization of iron stores (less evident with daprodustat, vadadustat and enarodustat). Kidney Disease: Improving Global Outcomes (KDIGO) recently reported the conclusions of the Controversies Conference on HIF-PHIs held in 2021. The goal of the present position paper endorsed by the Italian Society of Nephrology is to better adapt the conclusions of the latest KDIGO Conference on HIF-PHIs to the Italian context by reviewing the efficacy and safety of HIF-PHIs as well as their use in subpopulations of interest as emerged from more recent publications not discussed during the KDIGO Conference."

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

Chemistry, Analysis, and Biological Aspects of Daprodustat, A New Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitor: A Comprehensive Review. (PubMed, Mini Rev Med Chem) - "This review examines therapeutic, pharmacological, and analytical aspects related to the novel drug Daprodustat."

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

Nephrology: What You May Have Missed in 2023. (PubMed, Ann Intern Med) - "Four studies examined progression of chronic kidney disease or cardiovascular disease with respect to finerenone use, magnesium supplementation, iron markers, and COVID-19. Two studies examined treatments to improve specific aspects of chronic kidney disease management, including daprodustat to address anemia and patiromer to address hyperphosphatemia. One study showed that acetazolamide added to loop diuretics increased diuresis in acute decompensated heart failure across a wide range of renal function. Another study found that once-daily hydrochlorothiazide did not prevent kidney stone recurrence. Finally, an antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infection in frail older adults."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Geriatric Disorders • Heart Failure • Hematological Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Novel Coronavirus Disease • Renal Calculi • Renal Disease

Daprodustat: A Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor for Anemia of Chronic Kidney Disease. (PubMed, Ann Pharmacother) - "It was Food and Drug Administration approved in 2023 in patients already receiving dialysis for at least 4 months but not in non-dialysis patients. Long-term data for safety and additional benefits are pending."

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

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

Daprodustat. (PubMed, Hosp Pharm) - "Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433."

Journal • Review

Anemia Studies in CKD: Erythropoiesis Via a Novel PHI Daprodustat - Pediatric (ASCEND-P) (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Mar 2027 ➔ Jul 2030 | Trial primary completion date: Mar 2027 ➔ Jul 2030

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

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

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