New Oral Drug May Be Alternative to ESAs for Renal Anemia in Dialysis-Initiating Patients, New Study Shows

Dialysis patients are prone to renal anemia, and about 50% of chronic kidney disease (CKD) patients in China have substandard hemoglobin levels¹
.

In addition to active prevention, how to treat is also a concern for clinicians
.

Currently, erythropoiesis-stimulating agents (ESAs) and iron
.

However, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) has also gradually emerged, and has gradually entered clinical trials in various countries and has been successfully marketed
.

 On April 4, 2022, JAMA Internal Medicine published a report on the Daprodustat study of the HIF-PHI family.
The study shows that the oral drug Daparodustat is safe and effective, non-inferior to ESAs, and can be used as another powerful tool for intervening renal anemia in patients with initial dialysis²
.

Study Design The ASCEND-ID study is a prospective, randomized, open-label clinical study
.

Between May 11, 2017, and September 24, 2020, 90 hemodialysis centers in 14 countries participated in the study
.

The study was divided into 4 phases, namely screening, intervention, evaluation and follow-up
.

 Screening Phase: Patients participating in the screening were patients with advanced CKD who were scheduled to receive hemodialysis or peritoneal dialysis within 6 weeks or recently
.

Enrolled patients must meet the hemoglobin level between 8.
0 and 10.
5 g/dL, and the randomized hemoglobin level between 8.
0 and 11.
0 g/dL
.

In addition, iron supplementation is required to maintain serum ferritin levels >100 ng/ml and transferrin saturation >20%
.

In addition to meeting the above criteria, patients received no or limited ESA therapy
.

 Intervention Phase: Patients who successfully pass screening will be randomized 1:1 to Daparodustat and ESAs (darbepoetin alfa)
.

The patients in the Daparodustat group took Daparodustat orally every day to maintain the hemoglobin level between 10.
0 and 11.
0 g/dL
.

If necessary, patients need to supplement iron to maintain serum ferritin level >100ng/ml and transferrin saturation >20%
.

The ESA group received darbepoetin alfa
.

The two groups received a total of 28 weeks of intervention
.

 Assessment Phase: At Weeks 28-52, patients were assessed for achievement of the primary endpoint
.

The primary endpoint of this trial is to validate the efficacy of Daparodustat and ESAs
.

The change in the baseline hemoglobin level was used as the evaluation index
.

The secondary endpoint was to assess the safety of Daparodustat
.

 Follow-up Phase: At Weeks 56-58, patients will also be followed up
.

This phase primarily evaluates the secondary endpoint, the safety of daparodustat
.

RESULTS: A total of 312 patients were enrolled, aged 55 (IQR: 45-65) years, and 194 (62%) were male
.

They were randomly divided into two groups, 157 cases in Daparodustat group and 155 cases in ESAs group
.

During the evaluation period, the mean hemoglobin level was 10.
5 (SD: 1.
0) g/dL in the Daparodustat group and 10.
6 (SD: 0.
9) g/dL in the ESAs group
.

Compared with baseline, the difference between the two groups was -0.
10 g/dL (95% CI, -0.
34 to 0.
14 g/dL), indicating that Daparodustat was noninferior to ESAs
.

 In addition, monthly iron doses were reduced in both treatment groups from baseline to week 52, however, iron doses were not significantly reduced in the Daparodustat group compared with the ESAs group.
The difference was 19.
4 mg (95% CI, -11.
0 to 49.
9 mg)
.

 In terms of safety, the adverse event rate was 76% in the daparodustat arm compared to 72% in the ESAs arm
.

Overall safety was similar between the two groups, and no unexpected safety issues were found
.

 The study concluded that Daparodustat is a potential alternative to traditional ESAs for patients starting dialysis, and unlike ESAs, Daparodustat is an oral medication with higher adherence
.

 References: 1.
Expert Group on Diagnosis and Treatment of Renal Anemia Consensus of Nephrology Branch of Chinese Medical Association.
(2018).
Chinese Expert Consensus on Diagnosis and Treatment of Renal Anemia (2018 Revised Edition).
Chinese Journal of Nephrology, 34(11) : 860-866.
2.
Singh AK, Cizman B, Carroll K, et al.
Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in IncidentDialysis Patients: A Randomized Clinical Trial.
JAMA Intern Med.
2022 Apr 4.