Molidustat for Japanese Patients With Renal Anemia Receiving Dialysis

Abstract

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Molidustat for the treatment of anemia in Japanese patients undergoing peritoneal dialysis: a single‐arm, open‐label, phase 3 study

“…The proportion of patients with Hb levels in the target range decreased from baseline to Week 6, with a corresponding rise in the proportion of patients with Hb level below the target range. These observations are consistent with the onset of effect of molidustat of 6–8 weeks observed in the MIYABI ND‐M and HD‐M studies, as well as in phases 1 and 2 studies conducted in white and Asian patients (REF to MIAYBI ND‐M and HD‐M) ( 16 , 18 , 24 , 25 ). These adjustment phases observed for Hb level and for the proportion of patients with Hb levels in the target range are most likely a reflection of the time needed to reach an optimal molidustat dosage.…”

Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases

“…The endogenous EPO levels induced during treatment were close to the normal physiologic range of EPO, which proved its efficacy was non-inferior to ESAs (Akizawa et al, 2019c;Macdougall et al, 2019;Akizawa et al, 2021b). Molidustat has been shown to increase the availability of iron metabolism by the observation of changes in laboratory parameters (Macdougall et al, 2019), while the non-dropped levels of cholesterol and increasing levels of CRP may indicate a question of its safety (Akizawa et al, 2021b). In animal models, molidustat was shown to be effective in renal and inflammatory anemia, and unlike ESA therapy, it reduced blood pressure in an adenine-induced CKD model (Li L. et al, 2020).…”

“…Several phase 3 studies reported a good response of molidustat in Japanese patients with renal anemia who were not treated with dialysis and who were undergoing hemodialysis or peritoneal dialysis (Macdougall et al, 2019;Yamamoto et al, 2019;Yamamoto et al, 2021). The endogenous EPO levels induced during treatment were close to the normal physiologic range of EPO, which proved its efficacy was non-inferior to ESAs (Akizawa et al, 2019c;Macdougall et al, 2019;Akizawa et al, 2021b). Molidustat has been shown to increase the availability of iron metabolism by the observation of changes in laboratory parameters (Macdougall et al, 2019), while the non-dropped levels of cholesterol and increasing levels of CRP may indicate a question of its safety (Akizawa et al, 2021b).…”

“…These results indicate the potential usage of HIF-PHIs as an effective therapeutic strategy for treating atherosclerosis. However, the clinical data so far has not shown a beneficial effect and perhaps much longer studies are needed ( Martin et al, 2017 ; Haase et al, 2019 ; Akizawa et al, 2021b ).…”

Preclinical Characterization of Vadadustat (AKB-6548), an Oral Small Molecule Hypoxia-Inducible Factor Prolyl-4-Hydroxylase Inhibitor, for the Potential Treatment of Renal Anemia

“…Molidustat/BAY85-3934) but vadadustat and others (i.e. Roxadustat/FG-4592, Daprodustat/GSK1278863, Enarodustat/JTZ-951) do not (Brigandi et al, 2016;Holdstock et al, 2016;Akizawa et al, 2019;Akizawa et al, 2021) is an area for future studies. The observation that HIF-PHIs are erythropoietic at doses that do not stimulate VEGF also warrants investigation.…”