A phase 3b, multicenter, open‐label, single‐arm study of roxadustat within a US dialysis organization: The DENALI study

Abstract

IntroductionRoxadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor approved in several regions for the treatment of anemia of chronic kidney disease (CKD). DENALI, a phase 3b study, evaluated the efficacy, safety, and feasibility of roxadustat in patients with anemia of CKD receiving in‐center or home dialysis.MethodsEligible patients received open‐label roxadustat, dosed three times weekly for 24 weeks, with an optional extension of ≤1 year. Initial dosing depended on erythropoiesis‐stimulating agent (ESA) dose at screening for patients receiving ESAs (≥6 weeks) and weight‐based for those not (total <6 weeks). Primary efficacy endpoints were proportion of patients with mean hemoglobin (Hb) ≥10.0 g/dL averaged over Weeks 16–24, and mean Hb change from baseline to the average during Weeks 16–24. Treatment‐emergent adverse events (TEAEs) and treatment‐emergent serious adverse events (TESAEs) were assessed.FindingsOf 281 patients screened, 203 were treated and 201 included in the full analysis set. Overall, 166 patients completed the 24‐week treatment period and 126 continued into the extension period. Mean baseline Hb was 10.4 g/dL and 82.6% received in‐center hemodialysis. Overall, 84.6% of patients achieved a mean Hb ≥ 10.0 g/dL averaged Weeks 16–24. Mean (standard deviation) Hb change from baseline averaged Weeks 16–24 was 0.5 (1.0) g/dL. Prespecified subgroup analyses were consistent with primary analyses. Dosing adherence was 94%. Overall, 3.0% of patients received a red blood cell transfusion at up to Week 24. TEAEs and TESAEs were reported by 71.4% and 25.6% of patients, respectively. The most frequently reported TESAEs were COVID‐19 (n = 5; 2.5%), and acute myocardial infarction, pneumonia, and sepsis (each n = 4; 2.0%).DiscussionRoxadustat effectively achieved and/or maintained mean Hb levels ≥10.0 g/dL in patients receiving dialysis. The feasibility of incorporating oral roxadustat into dialysis organizations was successfully demonstrated with high dosing adherence. No new safety signals were identified.