MO542MOLIDUSTAT FOR ANAEMIA IN JAPANESE PATIENTS UNDERGOING PERITONEAL DIALYSIS: A SINGLE ARM, OPEN-LABEL, PHASE 3 STUDY
Authors: Akizawa Tadao , Nobori Kiyoshi , Matsuda Yoshimi , Taki Kentaro , Hayashi Yasuhiro , Hayasaki Takanori , Yamamoto Hiroyasu 
Published: May 2021

Abstract

Background and Aims
Erythropoiesis-stimulating agents (ESA) are the standard of care for anaemia due to chronic kidney disease (renal anaemia). Molidustat, a novel hypoxia-inducible factor prolyl hydroxylase (HIF–PH) inhibitor for the treatment of renal anaemia, could offer an alternative to ESAs. Molidustat was evaluated in the “molidustat once daily improves renal anaemia by inducing erythropoietin (MIYABI) program”, comprising five phase 3 studies. The present study investigated the safety and efficacy of molidustat in Japanese patients with renal anaemia undergoing peritoneal dialysis (PD) and previously treated with ESAs or not.

Method
This was a 36-week, open-label, single-arm, phase 3 study in Japanese patients ≥20 years with renal anaemia undergoing PD and not expected to start maintenance haemodialysis. Molidustat was administered once daily at a starting dose of 75 mg. Doses were titrated every 4 weeks based on the patient’s haemoglobin (Hb) response to the previous dose during visits to maintain the Hb level within the target range of ≥ 11.0 g/dL to &lt; 13.0 g/dL (Japanese guidelines). The primary efficacy outcome was the responder rate, defined as the proportion of patients who meet all of the following criteria: (1) mean Hb level during the evaluation period in the target range from week 30 to week 36; (2) ≥50% of Hb values within the target range during the evaluation period; (3) no rescue treatment before the end of the evaluation period. Other outcomes included mean Hb level during the evaluation period and its change from baseline, Hb level at each visit and the number of treatment-emergent adverse events (TEAEs).

Results
Overall, 51 patients received molidustat (49 ESA-treated; 2 ESA-untreated) and 36 (70.6%) completed treatment. Mean age was 63.3 years, mean body weight was 62.4 kg and 62.7% were male. Mean baseline Hb level was 11.19 g/dL and mean duration of peritoneal dialysis was 2.8 years. Over the study period, mean treatment duration was 200.8 days with a mean dosage of 93.8 mg/day.
The responder rate (95% confidence interval [CI]) during the evaluation period was 54.9% (40.3, 68.9). The proportions of patients meeting criterion (1), (2) or (3) were 54.9%, 58.8% and 92.2%, respectively. The mean (95% CI) for mean Hb level during the evaluation period was 11.18 (10.83, 11.54) g/dL and the mean (95% CI) for the change in mean Hb level during the evaluation period from baseline was 0.00 (–0.41, 0.41) g/dL. Mean Hb level stayed in the target range from week 12–36.
Of the 15 patients who did not complete treatment, 9 discontinued because of a TEAE, 4 initiated rescue treatment and 2 progressed to maintenance haemodialysis. Overall, 98.0% of patients experienced ≥1 TEAE during the study; most TEAEs were mild (49.0%) or moderate (37.3%) in intensity. The most common TEAEs were nasopharyngitis (35.3%), constipation and medical device site infection (11.8% each). No deaths were reported, and major adverse cardiovascular events occurred in 2.0% of patients.

Conclusion
In this phase 3, single-arm, open-label study, over 70% of patients completed the study and more than half of the patients met the responder criteria. Molidustat maintained Hb in the prespecified range (≥ 11.0 g/dL to &lt; 13.0 g/dL) and was well-tolerated over the 36 weeks of treatment. Molidustat offers a potential alternative to ESAs in patients with renal anaemia undergoing PD.