Vadadustat (symptomatic anaemia associated with dialysis-dependent chronic kidney disease) ' Addendum to Project A24-67 1 Translation of the addendum Vadadustat (symptomatische Anämie bei dialysepflichtiger chronischer Nierenerkrankung) – Addendum zum Projekt A24-67 (Dossierbewertung). Please note: This translation is provided as a service by IQWiG to English-language readers. However, solely the German original text is absolutely authoritative and legally binding. Vadadustat (symptomatic anaemia associated with dialysis-dependent chronic kidney disease) Addendum to Project A24-67 (dossier assessment)1 ADDENDUM Project: A24-106 Version: 1.0 Status: 31 Oct 2024 DOI: 10.60584/A24-106_en Addendum A24-106 Version 1.0 Vadadustat – Addendum to Project A24-67 31 Oct 2024 Institute for Quality
Vadadustat (anaemia associated with chronic kidney disease on dialysis) ' Benefit assessment according to ' 35a Social Code Book V 1 Translation of Sections I 1 to I 6 of the dossier assessment Vadadustat (symptomatische Anämie bei dialysepflichtiger chronischer Nierenerkrankung) – Nutzenbewertung gemäß § 35a SGB V. Please note: This translation is provided as a service by IQWiG to English -language readers. However, solely the German original text is absolutely authoritative and legally binding. Vadadustat (symptomatic anaemia associated with dialysis-dependent chronic kidney disease) Benefit assessment according to §35a SGB V1 EXTRACT Project: A24-67 Version: 1.0 Status: 29 Aug 2024 DOI: 10.60584/A24-67_en Extract of dossier assessment A24-67 Version 1.0 Vadadustat ( symptomatic anaemia
Vadadustat (Vafseo) - To treat anemia due to chronic kidney disease Drug Approval Package: VAFSEO * Skip to main content * Skip to FDA Search * Skip to footer links An official website of the United States governmentHere's how you know The .gov means it's official.Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government
Evaluating the safety and efficacy of vadadustat for the treatment of anemia associated with chronic kidney disease. The breakthrough in erythropoietin-stimulating agents in the 1990s improved the prognosis and treatment of complications in chronic kidney disease patients and renal anemia. Discovery of the novel molecular mechanisms for hypoxia-inducible factor (HIF) transcription factor under on the effectiveness and safety of vadadustat. A phase 3, randomized, open-label, clinical trial (PROTECT) demonstrated that vadadustat had the prespecified non-inferiority for hematologic efficacy as compared with darbepoetin alfa in non-dialysis-dependent patients not previously treated with ESA. However, vadadustat did not show non-inferiority in major adverse cardiovascular events in the non-US/non-Europe
Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies. Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease (CKD). The purpose of this post-hoc analysis was to investigate the factors affecting the responsiveness to vadadustat in anemia patients with nondialysis-dependent (NDD) or hemodialysis-dependent (HDD) CKD in two Japanese phase 3 studies. Of 151 and 162 patients enrolled in NDD-CKD and HDD-CKD studies, 136 and 140 patients, respectively, were included and divided into subgroups for the analysis. To assess vadadustat responsiveness, the resistance index was defined as the mean body weight-adjusted
Vadadustat Three Times Weekly in Patients With Anemia Due to Dialysis-Dependent CKD. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) may offer an alternative erythropoiesis-stimulating agents (ESA) for the treatment of anemia in the setting of CKD. To investigate the efficacy and safety of conversion from long-acting erythropoiesis-stimulating agent (ESA) methoxy polyethylene glycol-epoetin beta (MPG-EPO) to the oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) vadadustat 3-times-weekly versus maintenance on MPG-EPO. Phase 3b, open-label, noninferiority trial. Multicenter study in United States; 456 patients adults with anemia and dialysis-dependent chronic kidney disease. Participants were randomized 1:1:1 either to vadadustat (starting dose: 600 mg
Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis. Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label , sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear. We conducted a post hoc analysis of patients in the INNO2VATE trials
Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With Non-Dialysis-Dependent CKD: A Post Hoc Regional Analysis of the PRO(2)TECT Randomized Clinical Trial of ESA-Treated Patients. In the PROTECT trials, vadadustat was found to be noninferior to darbepoetin alfa in hematologic efficacy but not for major adverse cardiovascular events (MACE; all-cause death or nonfatal myocardial infarction or stroke) in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). We investigated the regional differences in MACE in the PROTECT trials. Phase 3, global, open-label, randomized, active-controlled clinical trial. A total of 1,725 erythropoiesis-stimulating agent (ESA)-treated patients with anemia and NDD-CKD. 1:1 randomization to receive vadadustat or darbepoetin
Safety Endpoints With Vadadustat Versus Darbepoetin Alfa in Patients With Non-Dialysis-Dependent CKD: A Post Hoc Regional Analysis of the PRO(2)TECT Randomized Clinical Trial of ESA-Naïve Patients. Prespecified analyses of the PROTECT trials comparing the safety of the oral hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat with darbepoetin alfa in patients with non-dialysis -dependent chronic kidney disease (NDD-CKD) found no difference in major adverse cardiovascular events (MACE; death from any cause or nonfatal myocardial infarction or stroke) among US patients and a higher risk among patients treated with vadadustat outside the United States. We investigated regional differences in MACE in the PROTECT trial that enrolled 1,751 patients previously untreated
Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD -CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo. In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD. Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production. In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52. A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production. We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial. In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.11). The mean differences between the groups in the change
Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials. Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production. To comprehensively analyze the safety profile of vadadustat in patients with dialysis-dependent and non
In Vitro and Clinical Pharmacokinetic Studies of the Effects of Iron-containing Agents on Vadadustat, an Oral Hypoxia-inducible Factor-Prolyl Hydroxylase Inhibitor. Vadadustat is an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor approved in Japan for the treatment of anemia in chronic kidney disease. This study investigated drug-drug interactions between vadadustat and oral iron supplements or iron-containing phosphate binders commonly used in Japanese clinical practice by conducting in vitro mechanistic and clinical pharmacokinetic studies. In the in vitro assessment, chelate formation of vadadustat with iron-containing agents was investigated in water and in a fed-state simulated intestinal fluid. Chelate formation was assessed by observation of a chelate-specific color
Cardiovascular safety and efficacy of vadadustat for the treatment of anemia in non-dialysis-dependent CKD: Design and baseline characteristics. Current clinical practice guidelines for anemia management in non-dialysis-dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia -inducible factor prolyl-hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PROTECT program comprises 2 global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N = 1751
Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials. Erythropoiesis-stimulating agents (ESAs) are currently the mainstay of treatment for anaemia of chronic kidney disease (CKD). Vadadustat is an investigational oral hypoxia-inducible factor prolyl -hydroxylase inhibitor that stimulates endogenous erythropoietin formation. The INNO2VATE programme comprises two studies designed to evaluate the safety and efficacy of vadadustat versus the ESA darbepoetin alfa in ameliorating anaemia in patients with dialysis-dependent CKD (DD-CKD). Here we describe the trial design along with patient demographics and baseline characteristics. Two Phase 3, open-label
Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study. Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. The efficacy and safety of vadadustat, compared with darbepoetin alfa, was determined in a Phase 3 double-blind study in Japanese anemic patients on hemodialysis. Patients receiving erythropoiesis-stimulating agents (ESAs) were randomized and switched to either vadadustat or darbepoetin alfa for 52 weeks. Doses were adjusted to maintain a hemoglobin (Hb) level of 10.0-12.0 g/dL. The primary endpoint was average Hb level at Weeks 20 and 24. Of the 323 randomized patients, 120 and 135 completed the 52-week treatment period
Vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, for treatment of anemia of chronic kidney disease: two randomized Phase 2 trials in Japanese patients. Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic kidney disease (CKD)-induced anemia. Two Phase 2, multicenter, double -blind, placebo-controlled studies randomized Japanese patients with nondialysis-dependent (NDD, n = 51) or dialysis-dependent (DD, n = 60) CKD-induced anemia to once-daily vadadustat (150, 300 or 600 mg) or placebo. A 6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat dose adjustment/maintenance period. The primary endpoint was the mean change in hemoglobin (Hb) level from