Daprodustat Dosing in ASCEND-D Trial Subgroups

Researchers led by Vivekanand Jha assessed the dose and number of dose adjustments for daprodustat (dapro) or erythropoiesis-stimulating agent (ESA) in prespecified subgroups in the ASCEND-D phase 3 trial. They presented results at the National Kidney Foundation Spring Clinical Meetings. Dapro is approved in the United States for treatment of anemia in stable hemodialysis patients.

Patients were randomized 1:1 to once-daily oral dapro or an injectable ESA. The researchers evaluated the median dose adjustment at week 52 of the study and the number of adjustments from day 1 until the end of treatment (EoT) by responsiveness to ESA at baseline. They evaluated the percentage difference in patients with ≥10 dose adjustments in ESA-hyporesponsive (ESA-HR) versus non–ESA-HR patients in each treatment arm post hoc.

At week 52, the median dose of dapro and ESA given to ESA-HR patients was higher than in non–ESA-HR patients. The median number of dose adjustments was lower for those receiving dapro versus ESA (median possible follow-up, dapro vs ESA: 2.58 vs 2.55 person-years).

The percentage of patients with dose adjustments ≤2 from day 1 to EoT was similar in ESA-HR and non–ESA-HR patients, for both dapro (21% vs 17%) and ESA (20% vs 17%). During the same period, the proportion of patients with ≥10 dose adjustments was not statistically different in ESA-HR patients compared with non–ESA-HR patients for dapro (27% vs 22%; P=.0556); however, it was slightly statistically higher in ESA-HR versus non–ESA-HR patients for the ESA treatment group (41% vs 30%; P=.0020).

The results suggest that, while dose adjustment considerations are similar for ESA-HR and non–ESA-HR patients, ESA-HR patients receiving ESAs may have different requirements for dose adjustments than non–ESA-HR patients.

Source: Jha V, Claggett B, Bhatt N, et al. Daprodustat (dapro) dosing among prespecified subgroups including erythropoiesis-stimulating agent hyporesponders (ESA-HR) in dialysis-dependent patients (pts) in the ASCEND program. Presented at the National Kidney Foundation Spring Clinical Meetings 2024; May 14-18, 2024; Long Beach, California.