Drug Profile of Daprodustat

Release date: 2026-07-16 17:28:08     Recommended: 9

Drug Profile of Daprodustat

Daprodustat is an oral small-molecule drug developed by GlaxoSmithKline Trading Services Limited, with the active ingredient daprodustat. The drug was originally planned for marketing authorization to treat adult patients with anemia due to chronic kidney disease (CKD), a condition extremely common in this patient population and significantly impacting quality of life and long-term prognosis.

The proposed indications cover two large patient groups: those receiving dialysis (dialysis partially replaces renal function by removing metabolic wastes and excess fluid from the blood) and non‑dialysis patients not yet on dialysis. This reflects the developer's intention to address therapeutic needs across different stages of the disease.

The dosage form is an oral tablet, convenient for home administration, offering potential advantages over traditional injectable erythropoiesis‑stimulating agents (such as epoetin alfa or darbepoetin alfa) in terms of ease of use and patient adherence. However, due to subsequent regulatory review outcomes, the drug's market launch did not proceed as originally planned in all settings.

Mechanism of Action of Daprodustat

In patients with chronic kidney disease, progressive loss of renal function leads to insufficient endogenous erythropoietin (EPO) production. EPO is a key hormone that stimulates bone marrow haematopoiesis and maintains normal red blood cell production. EPO deficiency directly causes anaemia, manifested as fatigue, shortness of breath, dizziness, and other symptoms.

The daprodustat in Daprodustat belongs to the class of hypoxia‑inducible factor prolyl hydroxylase (HIF‑PH) inhibitors. This enzyme degrades hypoxia‑inducible factor (HIF) under normal oxygen tension, whereas under hypoxic conditions, HIF is stabilised and initiates a series of adaptive gene expressions, including the EPO gene. By inhibiting HIF‑PH, daprodustat mimics a "hypoxic signal", prompting the body to increase endogenous EPO production, which in turn stimulates the bone marrow to produce more red blood cells, thereby raising haemoglobin levels and alleviating anaemic symptoms.

This mechanism differs from direct exogenous EPO supplementation, aiming for a more physiological regulation of erythropoiesis and possibly also modulating iron metabolism. However, in clinical studies, its long‑term safety, particularly regarding cardiovascular events and tumour risk, still requires sufficient data support, which was one of the key factors influencing the final regulatory conclusion.

How Effective Is Daprodustat?

In studies comparing with active controls (including recombinant human erythropoietin epoetin alfa and darbepoetin alfa), the treatment target was to maintain haemoglobin within the range of 10‑11 g/dL; while in placebo‑controlled trials, the target range was set at 11‑12 g/dL. The primary efficacy endpoints were the proportion of patients achieving and maintaining haemoglobin within the target range, and the change from baseline.

Study results showed that in dialysis patients, daprodustat effectively raised and maintained haemoglobin, with efficacy non‑inferior to standard EPO preparations; however, in non‑dialysis patients, data were relatively limited, and some potential safety signals were observed, such as thromboembolic events or worsening hypertension, which prompted regulatory agencies to exercise caution in assessing its risk‑benefit balance.