The treatment of anaemia associated with chronic kidney disease with Daprodustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor ( HIF-PHI ), based on the ASCEND phase III clinical trial programme, consists of five trials that all met their co-primary efficacy and safety endpoints.
Results from the key cardiovascular outcomes studies were published in the New England Journal of Medicine in November 2021 and included non-dialysis ( ASCEND-ND ) and dialysis ( ASCEND-D ) patients.
These studies have demonstrated that Daprodustat has improved and/or has maintained haemoglobin ( Hb ) within target level ( 10-11.5 g/dL ) without increased major adverse cardiovascular events ( MACE ) in the intention-to-treat populations in each pivotal study, compared to the standard of care, an erythropoietin stimulating agent ( ESA ), across both non-dialysis and dialysis patient settings.

The ASCEND Programme has assessed the efficacy and safety profile of Daprodustat for the treatment of anaemia of CKD across the disease pathway.
The Programme enrolled over 8,000 patients who were treated for up to 4.26 years.
Results from all five studies were presented at the American Society of Nephrology’s Kidney Week 2021.

Results from the two pivotal cardiovascular outcomes studies, ASCEND-ND and ASCEND-D, which investigated patients not on dialysis and on dialysis, respectively, were also published in the New England Journal of Medicine:

ASCEND-ND ( Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non-Dialysis ) enrolled 3,872 non-dialysis dependent patients with anaemia of CKD who were either switched from standard of care ( ESA ) or not currently receiving ESA therapy to receive daprodustat or ESA control ( Darbepoetin alfa ).
Iron management protocols were instituted across both arms in the study. The study met its primary efficacy and safety endpoints.
Results have shown Daprodustat improved and/or maintained Hb within target level ( 10-11.5 g/dL ) for these patients, and the primary safety analysis of the ITT population showed that Daprodustat achieved non-inferiority of MACE compared to ESA control.

ASCEND-D ( Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Dialysis ) enrolled 2,964 dialysis patients with anaemia of CKD who were switched to receive Daprodustat or ESA control from a standard of care ESA therapy.
A uniform iron management protocol was instituted across both arms of the study.
The study met its primary efficacy and safety endpoints.
The results have shown Daprodustat has improved or maintained Hb within target levels ( 10-11.5 g/dL ) for these patients, and the primary safety analysis of the ITT population showed that Daprodustat has achieved non-inferiority of MACE compared to ESA control.

Daprodustat, a HIF-PHI, belongs to a novel class of oral medicines indicated for the treatment of anaemia of CKD in adult patients not on dialysis and on dialysis.
Inhibition of oxygen-sensing prolyl hydroxylase enzymes stabilises hypoxia-inducible factors, which can lead to transcription of erythropoietin and other genes involved in the correction of anaemia, similar to the physiological effects that occur in the human body at high altitude.

Chronic kidney disease, characterised by progressive loss of kidney function, is an increasing global public health burden.
Risk factors for CKD include hypertension, diabetes, obesity and primary renal disorders.
Furthermore, CKD is an independent risk factor for cardiovascular disease.
Anaemia is an important and frequent complication of CKD.
However, it is often poorly diagnosed and undertreated in patients with early-stage CKD, such as those not on dialysis.
When left untreated or undertreated, anaemia of CKD is associated with poor clinical outcomes and leads to a substantial burden on patients and healthcare systems. ( Xagena )

Source: GSK ( GlaxoSmithKline ), 2022

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