Daprodustat is noninferior to the erythropoiesis-stimulating agent (ESA) darbepoetin in maintaining target-range hemoglobin (Hb) levels in patients receiving hemodialysis (HD), a new Japanese study finds.
Daprodustat is an investigational oral hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI).
In a phase 3 trial (NCT02969655), investigators randomly assigned 271 HD patients with renal anemia to receive daprodustat (4 mg once daily) or intravenous darbepoetin alfa (10-60 mg once weekly) according to their previous ESA dose. Dose adjustments occurred once every 4 weeks for daprodustat and once every 2 weeks for darbepoetin alfa.
At 40 to 52 weeks, mean hemoglobin (Hb) was within target range for both groups with no significant difference: 10.9 g/dL for daprodustat vs 10.8 g/dL for darbepoetin alfa, Tadao Akizawa, MD, PhD, of Showa University School of Medicine in Tokyo, Japan, and colleagues reported in the Clinical Journal of the American Society of Nephrology. The vast majority of patients in both groups maintained Hb levels within the target of 10.0 to 12.0 g/dL: 88% of daprodustat vs 90% of darbepoetin alfa users.
Over 52 weeks, daprodustat reduced geometric mean hepcidin levels compared with baseline significantly more than the ESA (-37% vs -20%, respectively). Both drugs decreased ferritin levels to a similar extent from baseline (-22% vs -20%, respectively) over 52 weeks. Fewer daprodustat users than darbepoetin alfa recipients required intravenous iron. The HIF-PHI also increased total iron-binding capacity.
The frequency of adverse events were generally similar between the daprodustat and darbepoetin alfa groups over 52 weeks, including those of special interest such as cardiovascular and ocular events. Contusion and diarrhea were reported more often in the daprodustat group.
“Effects of daprodustat on hemoglobin levels and iron parameters in our study were similar to the results observed with roxadustat;” Dr Akizawa’s team stated, “however, our study suggests the possibility of controlling hemoglobin with less IV iron use in patients treated with daprodustat, as physicians were allowed to select the route of iron administration as opposed to IV iron being limited to rescue use in the roxadustat study.”
The investigators strongly recommended monitoring Hbresponse upon daprodustat initiation.
Disclosure: This clinical trial was supported by GlaxoSmithKline. Please see the original reference for a full list of authors’ disclosures.
Akizawa T, Nangaku M, Yonekawa T, et al. Efficacy and safety of daprodustat compared with darbepoetin alfa in Japanese hemodialysis patients with anemia: A randomized, double-blind, phase 3 trial. Clin J Am Soc Nephrol. Published online July 28, 2020. doi:10.2215/CJN.16011219