Daprodustat: First Approval
- PDF / 776,952 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 57 Downloads / 235 Views
ADISINSIGHT REPORT
Daprodustat: First Approval Sohita Dhillon1
© Springer Nature Switzerland AG 2020
Abstract Daprodustat (DUVROQ) is a small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (PHD) developed by GlaxoSmithKline for the treatment of anaemia in patients with chronic kidney disease (CKD). Inhibition of PHD prevents degradation of hypoxia-inducible factor (HIF), leading to the production of erythropoietin and subsequent induction of erythropoiesis. In June, daprodustat received its first approval in Japan for the treatment of renal anaemia. Clinical studies of daprodustat are underway in multiple countries worldwide. This article summarizes the milestones in the development of daprodustat leading to this first approval for the treatment of renal anaemia.
Daprodustat (DUVROQ): Key points A small molecule PHD inhibitor is being developed by GlaxoSmithKline for the treatment of anaemia in patients with CKD Received its first approval on 29 June 2020 in Japan Approved for the treatment renal anaemia
1 Introduction Progressive chronic kidney disease (CKD) is associated with several serious complications, including anaemia, increased incidence of cardiovascular disease, hyperlipidaemia and metabolic bone disease [1]. Anaemia of CKD is largely the result of the diseased kidney being unable to adequately Enhanced material for this AdisInsight Report can be found at https://doi.org/10.6084/m9.figshare.12768536. This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through preclinical and clinical studies to market launch and beyond. * Sohita Dhillon [email protected] 1
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland 0754, New Zealand
respond to hypoxia and/or anaemia by inducing erythropoietin (EPO) production [2]. Other factors contributing to the development of anaemia include iron and vitamin deficiency, infection and inflammation [3]. Hypoxia-inducible factor (HIF) 1α and HIF2α are heterodimeric transcription factors mediating the cellular response to hypoxia by altering gene expression in certain cell types. This results in the increased production of EPO in the kidney and liver, which in turn promotes an erythropoietic response and upregulation of iron transport [2–4]. HIFα levels are regulated via the action of a family of HIF-prolyl hydroxylases (PHDs) that are important for maintaining the balance between oxygen availability and HIF activity [5]. PHDs tag HIFα for proteasomal degradation, and inhibition of these hydroxylases simulates conditions of mild hypoxia, leading to an erythropoietic response [5]. The central role of PHDs as the enzymatic gatekeepers of the adaptive response to hypoxia makes them attractive therapeutic targets for the treatment of anaemia. Daprodustat (DUVROQ) is a small molecule inhibitor of PHD developed by GlaxoSmithKline for the treatment of anaemia in patients with CKD. On 29 June 2020 [6], daprodustat received its fi
Data Loading...
