Daprodustat is a potential oral alternative to darbepoetin alfa for treating anemia of chronic kidney disease (CKD), recent study data suggest.

A prospective randomized clinical trial comparing daprodustat and darbepoetin alfa in incident dialysis patients with anemia demonstrated that both drugs increased and maintained hemoglobin levels to a similar extent and with a comparable safety profile.

In the 52-week ASCEND-ID (Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat in Incident Dialysis) trial, investigators randomly assigned 312 patients to receive daprodustat (157 patients), a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), or darbepoetin (155 patients), an erythropoiesis-stimulating agent (ESA).

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At baseline, both treatment arms had a mean hemoglobin level of 9.5 g/dL. During an evaluation period (weeks 28 to 52), the mean hemoglobin level was 10.5 g/dL among daprodustat recipients and 10.6 g/dL in the darbepoetin arm, with an adjusted mean treatment difference (-0.10) that was not statistically significant, Ajay K. Singh, MBBS, of Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues reported in JAMA Internal Medicine.

In addition, the investigators observed a reduction in mean monthly intravenous (IV) iron use from baseline to 52 weeks in both treatment groups, but daprodustat was not superior to darbepoetin in decreasing monthly IV iron use.

The study showed that daprodustat was effective in maintaining hemoglobin levels in patients with an unplanned dialysis start as well as in patients receiving peritoneal dialysis and those with inflammation.

The daprodustat and darbepoetin alfa groups had similar adverse event rates (76% and 72%, respectively. This study was not designed to evaluate major adverse cardiovascular events (MACEs), thromboembolic events, and hospitalization for heart failure. Investigators reported that a first MACE or a thromboembolic event occurred in 17% of the daprodustat group and 17% of the darbepoetin alfa group, whereas a first MACE or hospitalization for heart failure occurred in 15% of the daprodustat group and 12% of the darbepoetin alfa group.

“Based on the efficacy and short-term safety data in this study, daprodustat may represent a potential oral alternative to one of the conventional ESAs for patients with CKD who are starting dialysis,” Dr Singh’s team concluded.

Patients with advanced CKD were eligible for the trial if they planned to initiate dialysis within 6 weeks of screening or had started and received either hemodialysis or peritoneal dialysis.

The investigators enumerated the potential advantages of HIF-PHI agents compared with conventional ESAs, including oral dosing, physiologic endogenous erythropoietin levels, greater iron availability for erythropoiesis, and correction of anemia in patients who are hyporesponsive to ESAs. They noted that daprodustat increased hemoglobin levels to target levels as effectively as epoetin alfa or darbepoetin alfa in previous clinical trials in patients with CKD and those undergoing dialysis. The safety and efficacy of daprodustat, however, had not been examined in incident dialysis patients.

Disclosure: This research was supported by GlaxoSmithKline. Please see the original reference for a full list of disclosures.


Singh AK, Cizman B, Carroll K, et al. Efficacy and safety of daprodustat for treatment of anemia of chronic kidney disease in incident dialysis patients. A randomized clinical trial. JAMA Intern Med. Published online April 4, 2022. doi:10.1001/jamainternmed.2022.0605