Roxadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor developed to treat anemia in chronic kidney disease (CKD) patients. This Phase 3, randomized, open‐label, 24‐week study investigated the efficacy and safety of roxadustat in Japanese CKD patients with anemia on peritoneal dialysis (PD) who were previously treated or not treated with erythropoiesis stimulating agents (ESAs). Patients not previously receiving ESA (ESA‐Naïve group) were randomized to roxadustat at a starting dose of 50 or 70 mg three times weekly; patients previously receiving ESA (ESA‐Converted group) switched from ESA to roxadustat 70 or 100 mg three times weekly depending on the prior ESA dose. Outcomes included maintenance rate of average hemoglobin (Hb) level within 10–12 g/dL at weeks 18–24, cumulative response rate at end of treatment (Hb thresholds, 10.0 g/dL or 10.5 g/dL; Hb increase, ≥1.0 g/dL), and average Hb levels at weeks 18–24. Safety was assessed by occurrence of treatment‐emergent adverse events (TEAEs). Fifty‐six patients were enrolled (ESA‐Naïve, n = 13; ESA‐Converted, n = 43). Maintenance rates (weeks 18–24) were 92.3% (95% CI: 64.0–99.8; ESA‐Naïve) and 74.4% (95% CI: 58.8–86.5; ESA‐Converted). Cumulative response rate was 100.0% in the ESA‐Naïve group. Average Hb levels (weeks 18–24) were 11.05 g/dL (95% CI: 10.67–11.42; ESA‐Naïve) and 10.93 g/dL (95% CI: 10.73–11.13; ESA‐Converted). Common TEAEs included nasopharyngitis and back pain. Roxadustat was well tolerated and effective in maintaining target Hb levels in CKD patients on PD who were previously treated or not treated with ESA.

Roxadustat is a hypoxia‐inducible factor prolyl hydroxylase inhibitor approved in China for anemia of dialysis‐dependent chronic kidney disease (CKD). Japanese hemodialysis patients with anemia of CKD previously naïve to, or converted from, erythropoiesis‐stimulating agents (ESAs) were enrolled in two open‐label, noncomparative studies of titrated oral roxadustat administered three times weekly. ESA‐naïve patients (n = 75) were randomized to roxadustat (initial dose, 50 or 70 mg) for 24 weeks; ESA‐converted patients (n = 164) were assigned to roxadustat (initial dose, 70 or 100 mg based on prior ESA dose) for 52 weeks. Efficacy outcomes included average hemoglobin (Hb, weeks 18‐24 or 46‐52), change of Hb from baseline to weeks 18 to 24 (ΔHb18‐24) or weeks 46 to 52 (ΔHb46‐52), and maintenance rate (proportion of patients who achieved average Hb of 10.0‐12.0 g/dL for weeks 18‐24 or weeks 46‐52). Treatment‐emergent adverse events (TEAEs) were monitored. Mean (SD) Hb was 10.93 (0.79) g/dL (weeks 18‐24) (ESA‐Naïve Study), and 10.93 (0.69; weeks 18‐24) g/dL and 11.11 (0.67; weeks 46‐52) g/dL (ESA‐Converted Study). Mean (SD) ΔHb18‐24 was 2.26 (1.02) g/dL (ESA‐Naïve Study) and −0.03 (0.90) g/dL (ESA‐Converted Study); mean (SD) ΔHb46‐52 was 0.12 (0.83) g/dL (ESA‐Converted Study). The overall maintenance rate was 73.0% (54/74) (ESA‐Naïve Study) (weeks 18‐24), and 79.1% (129/163; weeks 18‐24) and 71.2% (116/163; weeks 46‐52) (ESA‐Converted Study). Nasopharyngitis was the most common TEAE. Two deaths, considered unrelated to roxadustat, occurred in the ESA‐Converted Study. Roxadustat effectively corrected and maintained Hb, regardless of previous ESA treatment, in Japanese anemic CKD patients on hemodialysis.

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These findings indicate that the expression of osteopontin is increased in BBB-damaged vessels in hypertensive SHRSP compared with that in vessels without BBB impairment in WKY rats, suggesting a role for osteopontin in BBB function.

The antibiotic thiazole compound siomycin, which we have found from the culture broth of Actinomycetes (strain No.806097) in search of antibody production inhibitor, showed the in vitro immunosuppressive property against B-cells stimulated with T-cell independent antigen DNP-LPS (dinitrophenyl-lipopolysaccharide) while it also showed inhibitory effect against Tcell proliferation. Its inhibitory mechanism was considered to be different from that of FK506, the representative of T-cell immunosuppressant. Moreover, siomycin showed inhibitory effect in both T-cell dependent and independent murine antibody production models and decreased the severity in murine collagen arthritis model. Therefore, siomycin is a unique immunosuppressant which has potential for the treatment of some antibody-mediated diseases.