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ROXADUSTAT FOR THE TREATMENT OF ANEMIA IN CHRONIC KIDNEY DISEASE PATIENTS NOT ON DIALYSIS: A PHASE 3 RANDOMIZED OPEN-LABEL ACTIVE-CONTROLLED STUDY (DOLOMITES)
JONATHAN BARRATT
; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
BRANISLAV ANDRIĆ
; Health Center Krusevac, Krusevac, Serbia
AVTANDIL TATARADZE
; National Center of Urology, Tbilisi, Georgia
MICHAEL SCHÖMIG
; Dialysis Center Heilbronn, Heilbronn, Germany
MICHAEL REUSCH
; Astellas Pharma Europe B.V., Leiden, Th e Netherland
UDAYA VALLURI
; Astellas Pharma Global Development, Inc., Northbrook, IL, USA
CHRISTOPHE MARIAT
; CHU St Etienne, Service Nephrologie Dialyse Transplantation, St Etienne, France
Abstract
Background: Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated for the treatment of anemia of chronic kidney disease (CKD). Methods: This randomized, open-label, active-controlled Phase 3 study compared roxadustat versus darbepoetin alfa (DA) in non-dialysis-dependent (NDD) CKD patients with anemia for ≤104 weeks. Doses were titrated to correct and maintain hemoglobin (Hb) within 10.0-12.0 g/dL. The primary endpoint was Hb response in the full analysis set, defi ned as Hb ≥11.0 g/dL and Hb change from baseline (BL; CFB) ≥1.0 g/dL in patients with BL Hb >8.0 g/dL or CFB ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL during the fi rst 24 weeks of treatment without rescue therapy (non-inferiority margin, -15%). The key secondary endpoints included change in low-density lipoprotein (LDL), time to fi rst intravenous (IV) iron use, change in mean arterial pressure (MAP), and time to hypertension occurrence. Adverse events were assessed. Results: Of 616 randomized patients (roxadustat, 323; DA, 293), 424 completed treatment (roxadustat, 215; DA, 209). Hb response with roxadustat was non-inferior to DA (roxadustat: 256/286, 89.5% versus DA: 213/273, 78.0%, difference 11.51%, 95% confi dence interval 5.66-17.36%). Roxadustat maintained Hb for up to 2 years. Roxadustat was non-inferior to DA for change in MAP and time to occurrence of hypertension, and superior for change in LDL and time to fi rst IV iron use. Safety profi les were comparable between the groups. Findings suggest that there was no difference between groups regarding the composite endpoints major adverse cardiovascular events (MACEs) and MACE+[MACE: 0.81 (0.52-1.25), p=0.339; MACE+: 0.90 (0.61-1.32), p=0.583]. Conclusions: Roxadustat is a viable option to treat anemia in NDD CKD patients maintaining Hb levels for up to 104 weeks.
Keywords
anemia; chronic kidney disease; erythropoietin; hemoglobin
Hrčak ID:
285258
URI
Publication date:
7.11.2022.
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