Roxadustat (evrenzo® tablet), a therapeutic drug for renal anemia: Pharmacological characteristics and clinical evidence in Japan

Abstract

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-a, 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).