Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients
Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients
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DOI：
10.1681/asn.2015030241
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发表时间：
2016-04-01
影响因子：
13.6
通讯作者：
Neff, Thomas B.
中科院分区：
文献类型：
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作者：
Besarab, Anatole;Chernyayskaya, Elena;Neff, Thomas B.
促红细胞生成素类似物和静脉（IV）铁剂治疗CKD贫血的安全性问题需要开发更安全的治疗方法。Roxadustat（FG-4592）是一种口服生物可利用的缺氧诱导因子（HIF）脯氨酰羟化酶抑制剂，通过HIF介导的转录促进协调红细胞生成。我们对贫血患者（7周内血红蛋白≥ 2.0 g/dl）进行了一项开放标签、随机血红蛋白（Hb）校正研究，无论基线铁补充状态、C反应蛋白水平、铁方案或透析方式如何。疗效可评价患者（n=55）12周内Hb较基线的平均+/- SEM最大变化（Delta Hb（max））（主要终点）为3.1 +/- 0.2 g/dl。在接受口服或IV铁的组中，+/- Hb（max）与无铁组相似且更大。96%的疗效可评价患者实现了Hb应答（Hb较基线增加>= 1.0 g/dl）。平均血清铁调素在研究开始后4周显著降低：未接受铁的HD患者（n=22）降低80%，接受口服铁的HD和PD患者（n=21）降低52%，接受IV铁的HD患者（n=9）降低41%。总之，无论基线铁补充状态或C反应蛋白水平如何，口服或IV补铁，罗沙司他在HD和PD患者中耐受良好，并纠正了贫血;它还降低了血清铁调素水平。
Safety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb = 2.0 g/dl within 7 weeks regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality. Mean +/- SEM maximal change in Hb from baseline (Delta Hb(max)), the primary endpoint, was 3.1 +/- 0.2 g/dl over 12 weeks in efficacy-evaluable patients (n=55). In groups receiving oral or IV iron, +/- Hb(max) was similar and larger than in the no-iron group. Hb response (increase in Hb >= 1.0 g/dl from baseline) was achieved in 96% of efficacy-evaluable patients. Mean serum hepcidin decreased significantly 4 weeks into study: by 80% in HD patients receiving no iron (n=22), 52% in HD and PD patients receiving oral iron (n=21), and 41% in HD patients receiving IV iron (n=9). In summary, roxadustat was well tolerated and corrected anemia in incident HD and PD patients, regardless of baseline iron repletion status or C-reactive protein level and with oral or IV iron supplementation; it also reduced serum hepcidin levels.