Roxadustat for the Maintenance Treatment of Anemia in Patients with End-Stage Kidney Disease on Stable Dialysis: A European Phase 3, Randomized, Open-Label, Active-Controlled Study (PYRENEES)

Csiky, Botond; Schömig, Michael; Esposito, Ciro; Barratt, Jonathan; Reusch, Michael; Valluri, Udaya; Sułowicz, Władysław

doi:10.1007/s12325-021-01904-6

Cited by 65 publications

(86 citation statements)

References 26 publications

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“…The hemoglobin response rate in another clinical trial was defined as an increase from the baseline of at least 1.0 g per deciliter in the hemoglobin level by Chen et al [ 16 ]. In PYRENEES (Roxadustat in the Treatment of Anemia in End-Stage Renal Disease Patients on Stable Dialysis), a Phase 3 controlled study, where 836 patients were randomized, the non-inferiority of Roxadustat versus ESA was declared for the change in Hb levels from baseline to the average of weeks 28-36 since the lower bound of the 95% CI was higher than 0.75 g/dL [ 17 ]. In our study, we choose a change of 0.75 g/dl as the hemoglobin response rate.…”

Section: Methodsmentioning

confidence: 99%

Safety and Effectiveness of Roxadustat in Dialysis-Dependent Patients With Renal Anemia: A Hospital-Based Cohort Study

Moussa¹,

Feng²,

Wang³

et al. 2022

Cureus

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Background Randomized controlled trials (RCTs) have shown the efficacy and safety of Roxadustat and conclude that it has the potential to change the treatment for anemia associated with chronic kidney disease. However, the experience of its use from clinical perspectives post-approval is lacking. Aim Using a clinical practice context, this study aims to compare Roxadustat's effectiveness and tolerability with Erythropoietin (EPO) in patients with renal anemia undergoing dialysis. Methods We examined the clinical records of patients with a diagnosis of renal anemia on dialysis who were prescribed Roxadustat or Erythropoietin at the department of nephrology of the First Affiliated Hospital of Gannan Medical University from January 2021 to December 2021. Eligible hemodialysis (HD) or peritoneal dialysis (PD) patients with renal anemia, aged >18 or <75 years, without infection, active bleeding, and malignancy were recruited. These patients received Roxadustat or EPO based on the preferential prescription choice made by the nephrologists of the department. We retrospectively attempted to determine the treatment response measured by the change in hemoglobin rate, from baseline up to six months. We also explored the impact of various factors on the treatment response and reported adverse events. Results A total of 106 patients have been included in the final analysis, with 53 patients in each group. The mean age of the study group was 49.9 ± 13.6 years with the main Hb level at the baseline of 8.1 g/dL ± 1.23 g/dl. The gain of hemoglobin from the baseline averaged over six months was 2.2 ± 2.11 g/dl in the Roxadustat group compared with 1.1 ± 1.67 g/dL in the EPO group ( p=0.01 ) . As compared to EPO,Roxadustat reduced the total cholesterol level by -0.59 ± 1.08 mmol/l versus -0.01 ± 1.28 mmol/l ( p=0012 ) and the low-density lipoprotein (LDL) cholesterol by -0.48 ± 1.07 mmol/l versus -0.47 ± 1.05 ( p=0.017 ) in the first three months. Associated factors with a non-response to treatment were age greater than 65 years (OR=6, 95% CI: 1.23-32.46, p=0.02 ), hypertension (OR=3.5, 95%CI: 0.89-13.25, p=0.060 ), and heart failure (OR=4.18, 95%CI:4.18 1.04-20.39, p=0.040 ). Although the proportion of hospitalization and infection was higher in the EPO group and the incidences of gastrointestinal symptoms (vomiting, nausea) and blood transfusions were higher in the Roxadustat group, there were no statistically significant differences. Conclusion Roxadustat improved hemoglobin compared to erythropoietin in patients undergoing dialysis with a safe profile but precautions should be taken for old patients with a cardiovascular medical history.

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Section: Methodsmentioning

confidence: 99%

Safety and Effectiveness of Roxadustat in Dialysis-Dependent Patients With Renal Anemia: A Hospital-Based Cohort Study

Moussa¹,

Feng²,

Wang³

et al. 2022

Cureus

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“…In another phase 3 trial, this time in 305 DD patients, roxadustat was statistically noninferior (difference, 0.2 ± 1.2 g/dl; 95% CI: −0.02 to 0.5) in maintaining hemoglobin compared to epoetin alfa [5 ▪▪ ]. More recently, the PYRENEES study in 836 dialysis patients [17 ▪ ], and the DOLOMITES study in 616 nondialysis patients [18 ▪ ] have confirmed the efficacy of roxadustat in maintaining hemoglobin levels in a target range of 10–12 g/dl up to 104 weeks of treatment.…”

Section: Effect On Hemoglobin and Anemiamentioning

confidence: 96%

Hypoxia-inducible factor prolyl hydroxylase enzyme inhibitors: ready for primetime?

Macdougall

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewHypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors have recently been developed as a new treatment for anemia associated with chronic kidney disease (CKD). Several of these have been approved in Europe (roxadustat), China, and Japan, but none approved in the United States to date, although daprodustat has been submitted as a new drug application to the Food and Drug Administration. The aim of this review is to critically appraise the available data, particularly the most recent publications, and offer a personal viewpoint on whether or not these drugs are ready for primetime. Recent findingsThe efficacy of HIF prolyl hydroxylase inhibitors in improving CKD anemia and maintaining a higher hemoglobin is undisputed, but there remain some concerns about safety, particularly in the long term. Some of the safety concerns may result from an exaggerated pharmacological response, while other potential adverse effects could be due to transcriptional effects of these agents beyond genes involved in erythropoiesis. SummaryHIF prolyl hydroxylase inhibitors are already being used in clinical practice in several countries of the world, and ongoing research is being conducted to define the role of these drugs not only in the management of anemia but also beyond into other clinical settings.

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“…Roxadustat (FG‐4592) is a hypoxia‐inducible factor prolyl hydroxylase inhibitor (HIF‐PHI), which is a new class of oral agents for the treatment of CKD anaemia 7 . In phase 3 clinical trials, roxadustat proved effective in correcting anaemia in non‐dialysis CKD patients or maintaining haemoglobin (Hb) after switching from ESA in dialysis patients 8–13 . Roxadustat has been marketed in China for CKD patients and covered by medical insurance for 3 years.…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…7 In phase 3 clinical trials, roxadustat proved effective in correcting anaemia in non-dialysis CKD patients or maintaining haemoglobin (Hb) after switching from ESA in dialysis patients. [8][9][10][11][12][13] Roxadustat has been marketed in China for CKD patients and covered by medical insurance for 3 years. Because HIF-PHIs can regulate the expression of erythropoietin and iron metabolism genes, 14 roxadustat may be effective in correcting ESA-hyporesponsive anaemia.…”

mentioning

confidence: 99%

Addition of roxadustat to erythropoiesis‐stimulating agent ( ESA ) effectively corrects ESA ‐hyporesponsive anaemia in patients on peritoneal dialysis

Dai

Chen

Hao

et al. 2022

Clinical Pharmacy Therapeu

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What Is Known and Objective Erythropoiesis‐stimulating agent (ESA) hyporesponsiveness is an important cause for the undertreatment of anaemia. A decrease in haemoglobin (Hb) levels was observed during the initial stage of the conversion from ESA to roxadustat. The study aims to investigate the effectiveness and safety of adding roxadustat to an ESA for the treatment of ESA‐hyporesponsive anaemia in patients on peritoneal dialysis (PD). Methods Patients on PD with ESA‐hyporesponsive anaemia were enrolled from January 2020 to April 2020 with a 24‐week follow‐up period. Patients were treated with roxadustat at a starting dose of 50 or 100 mg thrice weekly without changing the ESA dose. Roxadustat and ESA dose adjustments were made as needed to maintain Hb levels within 11.0 to 13.0 g/dl. Efficacy outcomes and safety were assessed. Results and Discussion Nine patients were recruited in the study. Both the cumulative responsive rate and maintenance rate of Hb > 11 g/dl were 100%. Six patients required ESA dose reduction from ≥15,000 UI/week to ≤7000 IU/week at week 24. No drug‐related severe adverse events were observed in this study. What Is New and Conclusion The addition of roxadustat effectively and smoothly corrected anaemia in patients who were hyporesponsive to ESA, and permitted reduction of the ESA dose.

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Roxadustat for the Maintenance Treatment of Anemia in Patients with End-Stage Kidney Disease on Stable Dialysis: A European Phase 3, Randomized, Open-Label, Active-Controlled Study (PYRENEES)

Cited by 65 publications

References 26 publications

Safety and Effectiveness of Roxadustat in Dialysis-Dependent Patients With Renal Anemia: A Hospital-Based Cohort Study

Safety and Effectiveness of Roxadustat in Dialysis-Dependent Patients With Renal Anemia: A Hospital-Based Cohort Study

Hypoxia-inducible factor prolyl hydroxylase enzyme inhibitors: ready for primetime?

Addition of roxadustat to erythropoiesis‐stimulating agent ( ESA ) effectively corrects ESA ‐hyporesponsive anaemia in patients on peritoneal dialysis

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