Fresenius Medical Care, Global Medical Office, Waltham, Massachusetts, USA.
Nephrology & Hypertension Associates Ltd, Tupelo, Mississippi, USA.
Hemodial Int. 2024 Jan;28(1):59-71. doi: 10.1111/hdi.13122. Epub 2023 Oct 24.
Roxadustat 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.
Eligible 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.
Of 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%).
Roxadustat 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.
罗沙司他是一种口服低氧诱导因子脯氨酰羟化酶抑制剂，已在多个地区获得批准，用于治疗慢性肾脏病（CKD）贫血。DENALI 是一项 3b 期研究，评估了罗沙司他在接受中心或家庭透析的 CKD 贫血患者中的疗效、安全性和可行性。
符合条件的患者接受罗沙司他开放标签治疗，每周 3 次，持续 24 周，可选延长治疗≤1 年。起始剂量取决于筛选时接受促红细胞生成素刺激剂（ESA）治疗（≥6 周）患者的 ESA 剂量和未接受ESA 治疗（总时间<6 周）患者的体重。主要疗效终点为第 16-24 周平均血红蛋白（Hb）≥10.0 g/dL 的患者比例和第 16-24 周平均基线至 Hb 变化。评估治疗出现的不良事件（TEAE）和治疗出现的严重不良事件（TESAEs）。
在 281 名筛选患者中，有 203 名接受了治疗，201 名纳入全分析集。总体而言，166 名患者完成了 24 周的治疗期，126 名患者继续进入延长期。平均基线 Hb 为 10.4 g/dL，82.6%接受中心血液透析。总体而言，84.6%的患者在第 16-24 周的平均 Hb 达到≥10.0 g/dL。第 16-24 周平均（标准差）Hb 变化从基线平均为 0.5（1.0）g/dL。预先指定的亚组分析与主要分析一致。药物依从性为 94%。总体而言，3.0%的患者在 24 周时接受了红细胞输注。分别有 71.4%和 25.6%的患者报告出现治疗出现的不良事件和治疗出现的严重不良事件。报告最多的治疗出现的严重不良事件为 COVID-19（n=5；2.5%），急性心肌梗死、肺炎和败血症（各 n=4；2.0%）。
罗沙司他有效地使接受透析的患者达到并/或维持平均 Hb 水平≥10.0 g/dL。高药物依从性成功证明了将口服罗沙司他纳入透析组织的可行性。未发现新的安全性信号。
