The treatment was comparable to darbepoetin alfa in treating patients with chronic kidney disease who were not undergoing dialysis.
Daprodustat might be comparable in reducing major adverse cardiovascular events and maintaining hemoglobin levels to darbepoetin alfa in patients with chronic kidney disease with anemia who are not undergoing dialysis.
A team, led by Ajay K. Singh, MB, BS, MBA, Senior Associate Dean for Postgraduate Medical Education at Harvard Medical School and Director, Master in Medical Sciences in Clinical Investigation (MMSCI) Program, compared the 2 treatments in this patient population for 52 weeks.
Daprodustat, an oral hyperoxia-inducible factor prolyl hydroxylase inhibitor, that has shown promise, but it is unknown whether it is effective and safe for patients with chronic kidney disease who are not undergoing dialysis, compared to conventional erythropoiesis-stimulating agent darbepoetin alfa.
In the randomized, open-label, phase 3 study with blinded adjudication of cardiovascular outcomes, the investigators compared the study drug with darbepoetin alfa for the treatment of anemia for patients with chronic kidney disease not undergoing dialysis. They identified and enrolled 3872 patients.
The mean baseline hemoglobin levels was similar between the daprodustat and darbepoetin alfa cohorts.
The investigators sought primary outcomes of the mean change in the hemoglobin level from baseline to weeks 28-52, as well as the first occurrence of a major adverse cardiovascular event, including a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.
Overall, the mean change in the hemoglobin level from baseline to weeks 28-52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% CI, 0.03-0.13). This met the prespecified noninferiority margin of -0.75 g per deciliter.
During a median follow-up period of 1.9 years, a first major adverse cardiovascular event occurred in 19.5% (n = 378) of the patient population in the daprodustat arm, compared to 19.2% (n = 371) in the darbepoetin alfa group (HR, 1.03; 95% CI, 0.89-1.19).
This also met the prespecified noninferiority margin of 1.25.
In addition, the percentage of patients with adverse events were similar between the daprodustat and darbepoetin alfa arms.
“Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes,” the authors wrote.
In 2021, GlaxoSmithKline announced the positive headline results from 5 phase 3 studies as part of the ASCEND program evaluating daprodustat.
The treatment met the primary efficacy endpoint in each of the 5 studies, as well as the key cardiovascular outcomes showing daprodustat was non-inferior when compared to an ESA, the standard treatment for this population, in the risk of major adverse cardiovascular events for both non-dialysis (ASCEND-ND) and dialysis patients (ASCEND-D).
Also included in the ASCEND program are studies focused on incident dialysis for patients just beginning dialysis (ASCEND-ID), a quality of life examination (ASCEND-NHQ), and a trial looking at three-times weekly dosing regimens (ASCEND-TD).
ASCEND involved more than 8000 patients treated for up to 3.75 years.
The study, “Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis,” was published online in the New England Journal of Medicine.