Ugawa Tohru, Ashizaki Mizue, Murata Asami, Majikawa Yoshikatsu
Research Program Management, Drug Discovery Research, Astellas Pharma Inc.
Japan-Asia Clinical Development II, Development, Astellas Pharma Inc.
Nihon Yakurigaku Zasshi. 2021;156(3):187-197. doi: 10.1254/fpj.21001.
Roxadustat (Evrenzo tablet) is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. Roxadustat has been approved for the treatment of renal anemia in patients on dialysis in September 2019 in Japan. By inhibiting HIF-PH, roxadustat suppresses the degradation of HIF-α, a subunit of the heterodimeric transcription factor HIF, leading to its accumulation and activation of the HIF pathway. Similar to activation of the HIF pathway in response to hypoxia, the production of endogenous erythropoietin is increased and erythropoiesis is stimulated. Moreover, roxadustat stimulates erythropoiesis efficiently by improving iron bioavailability. The efficacy and mechanism of action of roxadustat have been detailed in non-clinical pharmacology studies. Rat models of anemia demonstrated efficacy of roxadustat in correcting anemia and changes in gene expression leading to increased iron bioavailability. Four phase 3 clinical studies in Japan clearly demonstrated the efficacy of roxadustat in patients with renal anemia on dialysis. Roxadustat showed an acceptable safety profile, and the incidences and types of adverse events and serious adverse events reported in the clinical studies were similar with those predicted to occur in these patient population. Since roxadustat is an oral drug, concerns present with erythropoiesis-stimulating agents (ESAs) such as the risk of infection to the medical staff due to accidental needle-stick, pain during ESA injection in patients and burden on patients to visit a hospital, can be avoided or reduced. In November 2020, roxadustat has also been approved for the treatment of renal anemia in patients not on dialysis (data not shown in this article).
罗沙司他（爱瑞卓片）是一种口服的低氧诱导因子脯氨酰羟化酶（HIF-PH）抑制剂。2019年9月，罗沙司他在日本被批准用于治疗透析患者的肾性贫血。通过抑制HIF-PH，罗沙司他可抑制异二聚体转录因子HIF的一个亚基HIF-α的降解，导致其积累并激活HIF通路。与低氧反应时HIF通路的激活类似，内源性促红细胞生成素的产生增加，红细胞生成受到刺激。此外，罗沙司他通过提高铁的生物利用度有效刺激红细胞生成。罗沙司他的疗效和作用机制已在非临床药理学研究中详细阐述。贫血大鼠模型证明了罗沙司他在纠正贫血以及导致铁生物利用度增加的基因表达变化方面的疗效。日本的四项3期临床研究清楚地证明了罗沙司他对透析肾性贫血患者的疗效。罗沙司他显示出可接受的安全性，临床研究中报告的不良事件和严重不良事件的发生率及类型与这些患者群体中预计发生的情况相似。由于罗沙司他是一种口服药物，可以避免或减少促红细胞生成素（ESA）存在的问题，如意外针刺导致医护人员感染的风险、患者接受ESA注射时的疼痛以及患者就医的负担。2020年11月，罗沙司他也已被批准用于治疗非透析患者的肾性贫血（本文未显示相关数据）。
