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

Abstract

This 36-week, open-label, single-arm, phase 3 study investigated the safety and efficacy of molidustat in Japanese patients with renal anemia undergoing peritoneal dialysis. Molidustat was titrated every 4 weeks to maintain Hb levels within the target range (≥11.0 and <13.0 g/dL). The primary efficacy outcome was the responder rate, defined as the proportion of patients who met all of the following criteria:(1) mean Hb levels in the target range during the evaluation period (Weeks 30-36);(2) ≥50% of Hb values within the target range during the evaluation period; and (3) no rescue treatment before the end of the evaluation period. Overall, 51 patients received molidustat. The responder rate (95% CI) during the evaluation period was 54. 9% (40.3, 68.9). Overall, 98.0% of patients experienced at least 1 adverse event during the study. No deaths were reported. Molidustat maintained Hb levels in the prespecified range in more than half of the patients and was well tolerated.

Scaffold hopping strategy to derive 4‐hydroxy‐1‐alkyl‐2‐oxo‐1,2‐dihydrothieno[2,3‐b:4,5‐b′]dipyridine‐3‐carbonylglycine derivatives as a novel hypoxia‐inducible factor prolyl hydroxylase domain inhibitor for the potential treatment of chronic kidney disease anemia

“…Prolyl hydroxylase domain (PHD) inhibitors have been developed for the treatment of anemia in chronic kidney disease (CKD) in clinical settings. Roxadustat (FG‐4592) developed by Fibrogen, 1 vadadustat (AKB‐6548) by Akebia, 2 daprodustat (GSK1278863) by GlaxoSmithKline (GSK), 3 and molidustat (BAY 85‐3934) by Bayer 4 are the examples of such inhibitors that are currently being used in late‐stage clinical studies (Figure 1). Recently, daprodustat has been accepted by the US Food and Drug Administration (FDA) for New Drug Application (NDA), 5 whereas roxadustat and vadadustat have been denied the FDA approval.…”

“…Furthermore, the inhibitory activity of the dihydropyridothienopyrazine derivative with the Northo-chlorobenzyl group against PHD2 was maintained (Table 2, 12k). However, the significance of the position of nitrogen in the third ring was repeatedly confirmed through the 1,2-dihydrothieno[3,2-b:4,5-b 0 ]dipyridine and 1,2-dihydrobenzo [4,5]thieno [3,2-b]pyridine derivatives that exhibited very weak inhibitory activity with IC 50 values of >15 μM (Table 2, 12l and 12m). After determining the 2, 12n-12q).…”

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

“…When performed, Hb changes induced by HIF-PHIs and comparator were similarly independent from the type of dialysis. One 36-week, open-label, single-arm trial conducted in Japan specifically focused on this population by enrolling 68 PD patients [61]. At baseline, 51% of the patients had Hb levels within the target range of 11.0-13.0 g/dL; after switching to molidustat, the response rate increased to 76% (95% CI 59-88), with less than 3% of the patients requiring rescue therapy [26].…”