Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study

Abstract

Background Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. Methods The efficacy and safety of vadadustat, compared with darbepoetin alfa, was determined in a phase 3 double-blind study in Japanese anemic patients on hemodialysis. Patients receiving erythropoiesis-stimulating agents (ESAs) were randomized and switched to either vadadustat or darbepoetin alfa for 52 weeks. Doses were adjusted to maintain a hemoglobin level of 10.0–12.0 g/dL. The primary endpoint was average hemoglobin level at weeks 20 and 24. Results Of 323 randomized patients, 120 and 135 completed the 52-week treatment period in the vadadustat and darbepoetin alfa groups, respectively. The average hemoglobin levels at weeks 20 and 24 (least square mean [LSM] and 95% confidence interval [CI]) were 10.61 (10.45–10.76) and 10.65 (10.50–10.80) g/dL in the vadadustat and darbepoetin alfa groups, respectively, demonstrating vadadustat’s non-inferiority to darbepoetin alfa (difference, −0.05 g/dL; 95% CI, −0.26–0.17). In both groups, the mean hemoglobin levels were maintained within the target range for 52 weeks. Furthermore, irrespective of patient backgrounds, the LSMs at week 52 were within the target range. The most common adverse events were nasopharyngitis, diarrhea, and shunt stenosis, which occurred at similar frequencies in both groups. No new safety concerns were identified. Conclusions Vadadustat was as well tolerated and effective as darbepoetin alfa in maintaining hemoglobin levels within the target range. The findings suggest that vadadustat can be an alternative to ESA in the management of anemia in Japanese hemodialysis patients receiving ESA (Clinical Trials.gov, NCT03439137).

Molidustat for Japanese Patients With Renal Anemia Receiving Dialysis

“…13,14 In the present study, the high incidences of TEAEs observed in both treatment groups were not surprising in this patient population and were in line with published data. 16,18 There were numeric imbalances in the incidences of TEAEs resulting in discontinuation (including neoplasms considered by the investigator to be unrelated to study drug), of ocular AEs, of moderate and severe TEAEs, and in the number of patients who received rescue treatment that favored darbepoetin. Interestingly, in patients not receiving dialysis, the incidences of neoplasms and ocular AEs were similar between molidustat (3.7% and 19.5%, respectively) and darbepoetin (4.9% and 20.7%, respectively).…”

Treatment of Anemia in Kidney Disease: Beyond Erythropoietin

“…Vadadustat A 52-week phase 3 study of vadadustat vs. darbepoetin among 323 DD-CKD patients in Japan revealed efficacy noninferiority for vadadustat and no safety concerns. 58 In an open-label phase 3 24-week study of 42 Japanese PD patients vadadustat was well-tolerated and maintained target Hb levels. 59 The global phase 3 program for vadadustat includes INNO 2 VATE for DD-CKD patients 60 and PRO 2 TECT for NDD-CKD patients.…”

Managing Anemia across the Stages of Kidney Disease in Those Hyporesponsive to Erythropoiesis-Stimulating Agents

“…Collectively, data from clinical trials of HIF-PH inhibitors, namely roxadustat [115][116][117][118][119][120][121][122][123][124][125][126][127], daprodustat [128][129][130][131][132][133][134][135], desidustat [136], enarodustat [137,138], molidustat [139][140][141][142][143], and vadadustat [144][145][146][147][148][149], have clearly shown these agents are efficacious in increasing Hb and decreasing hepcidin levels in patients with anemia of CKD (Table 2). Indeed, a recent meta-analysis of 22 trials found that HIF-PH inhibitors provided a 0.96 and 1.78 g/dL greater weighted mean increases of Hb levels from baseline compared with control (placebo or ESA) in patients with DD-CKD or NDD-CKD, respectively [150].…”