Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants with chronic kidney disease

Abstract

BackgroundThis study assessed the short-term safety and efficacy of daprodustat (an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor) to achieve a target hemoglobin in patients with anemia of chronic kidney disease (CKD).MethodsPatients (n = 252) with Stages 3–5 CKD not receiving dialysis were enrolled in this 24-week, multicenter trial [hemoglobin entry criteria: 8–10 g/dL (Cohort 1) or 8–11 g/dL (Cohort 2) for recombinant human erythropoietin (rhEPO)-naïve participants; 9–10.5 g/dL (Cohort 1) or 9–11.5 g/dL (Cohort 2) for rhEPO users]. rhEPO-naïve participants were randomized 3:1 to daprodustat (1, 2 or 4 mg) or control (rhEPO per standard of care). rhEPO users were randomized 1:1 to daprodustat 2 mg or control. Study medication was titrated to maintain hemoglobin 9–10.5 g/dL (Cohort 1) or 10–11.5 g/dL (Cohort 2). Hemoglobin, iron metabolism markers and safety parameters were measured every 4 weeks.ResultsMean hemoglobin levels at Week 24 were 10.2 g/dL (Cohort 1) and 10.9 g/dL (Cohort 2) in the daprodustat group and 10.7 g/dL (Cohort 1) and 11.0 g/dL (Cohort 2) in the control group. Participants had hemoglobin levels within the target range a median of 82% and 66% of the time between Weeks 12 and 24 in the daprodustat and control groups, respectively. The adverse event profile was consistent with clinical events in the CKD population.ConclusionsDaprodustat effectively maintained target hemoglobin over 24 weeks in CKD patients with anemia who were rhEPO naïve or had switched from existing rhEPO therapy.

A 24‐Week Anemia Correction Study of Daprodustat in Japanese Dialysis Patients

“…HIF-PHIs stimulate erythropoiesis by inhibiting HIFprolyl hydroxylases (PHD1, PHD2, PHD3), leading to activation of HIF-responsive genes that regulate the tissue response to hypoxia, including the EPO gene and genes involved in iron homeostasis (14). In a phase 2 study in anemic patients with stages 3 to 5 CKD who were rhEPO naïve or had switched from existing rhEPO therapy, daprodustat increased and effectively maintained target hemoglobin levels within a narrow prespecified range over 24 weeks without any adverse trends reported (15). Another phase 2 study in hemodialysis patients showed that daprodustat 4 to 10 mg once daily produced dosedependent changes in hemoglobin levels over the first 4 weeks after patients were switched from a stable dose of rhEPO.…”

Daprodustat: First Approval

“…Another 24-week, randomized, open-label, multicentre, phase 2b study (NCT01977573) showed that daprodustat effectively achieved/maintained target Hb levels over 24 weeks in non-dialysis-dependent CKD-3/4/5 patients with anaemia who were rhEPO naïve or who had switched from existing rhEPO therapy [18]. Patients who were rhEPO naïve (n = 180) were randomized 3:1 to receive daprodustat (1, 2 or 4 mg based on baseline Hb) once daily or control (rhEPO per standard of care), and rhEPO-users (n = 72) were randomized 1:1 to daprodustat 2 mg once daily or control (rhEPO per standard of care) for 4 weeks, thereafter daprodustat doses could be adjusted to achieve and maintain target Hb levels (9-10.5 g/dL in Cohort 1 and 10-11.5 g/dL in Cohort 2).…”

Ckj consolidation among Q1 Urology and Nephrology journals

“…Top-cited articles also included those related to CKD complications, such as cognitive function [ 6 ] and frailty [ 12 ], as well as management of complications such as pain [ 4 ] and anaemia [ 32 , 38 ]. Anaemia management focused on early clinical trials the novel drug family of oral hypoxia-inducible factor activators, such as daprodustat [ 32 , 38 ].…”