Background Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated for treatment of anaemia of chronic kidney disease (CKD). Methods This randomised, open-label, active-controlled phase 3 study compared roxadustat versus darbepoetin alfa (DA) in non–dialysis-dependent (NDD) CKD patients with anaemia for ≤104 weeks. Doses were titrated to correct and maintain haemoglobin within 10.0–12.0 g/dL. The primary endpoint was haemoglobin response in the full analysis set (FAS), defined as haemoglobin ≥11.0 g/dL and haemoglobin change from baseline (CFB) ≥1.0 g/dL in patients with baseline haemoglobin >8.0 g/dL or CFB ≥2.0 g/dL in patients with baseline haemoglobin ≤8.0 g/dL during the first 24 weeks of treatment without rescue therapy (noninferiority margin, -15%). Key secondary endpoints included change in low-density lipoprotein (LDL), time to first intravenous iron use, change in mean arterial pressure (MAP), and time to hypertension occurrence. Adverse events were assessed. Results Of 616 randomised patients (roxadustat, 323; DA, 293), 424 completed treatment (roxadustat, 215; DA, 209). Haemoglobin response with roxadustat was noninferior to DA (roxadustat: 256/286, 89.5% vs. DA: 213/273, 78.0%, difference 11.51%, 95% confidence interval, 5.66-17.36%). Roxadustat maintained haemoglobin for up to 2 years. Roxadustat was noninferior to DA for change in MAP and time to occurrence of hypertension and superior for change in LDL and time to first intravenous iron use. Safety profiles were comparable between groups. Findings suggest that there was no difference between groups regarding the composite endpoints major adverse cardiovascular events (MACE) and MACE + (MACE: 0.81 [0.52, 1.25], P = 0.339; MACE+: 0.90 [0.61, 1.32], P = 0.583). Conclusion Roxadustat is a viable option to treat anaemia in NDD CKD patients maintaining haemoglobin levels for up to 104 weeks.

Background Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for the treatment of chronic kidney disease (CKD) anemia. Methods This phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with stage 3-5 CKD not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52-104 weeks. This study examined two primary efficacy endpoints: European Union (EMA) - hemoglobin (Hb) response, defined as Hb ≥ 11.0 g/dL that increased from baseline by ≥ 1.0 g/dL in patients with Hb > 8.0 g/dL or ≥ 2.0 g/dL in patients with baseline Hb ≤ 8.0 g/dL, without rescue therapy, during the first 24 weeks of treatment; United States (FDA) - change in Hb from baseline to the average Hb level during Weeks 28-52, regardless of rescue therapy. Secondary efficacy endpoints and safety were examined. Results A total of 594 patients were analyzed (roxadustat: 391; placebo: 203). Superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints: Hb response (odds ratio: 34.74 [95% CI: 20.48, 58.93]) and change in Hb from baseline (roxadustat - placebo: +1.692 [95% CI: 1.52, 1.86]; both P<0.001). Superiority of roxadustat was demonstrated for LDL cholesterol change from baseline, and time to first use of rescue medication (both P<0.001). The incidences of treatment-emergent adverse events were comparable between groups (roxadustat: 87.7%, placebo: 86.7%). Conclusions Roxadustat demonstrated superior efficacy versus placebo both in terms of Hb response rate and change in Hb from baseline. The safety profiles of roxadustat and placebo were comparable.

Introduction: Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia of chronic kidney disease (CKD). This European, phase 3, randomized, open-label, active-controlled study investigated efficacy and safety of roxadustat in patients with endstage kidney disease on dialysis for at least 4 months. Methods: Patients were randomized to switch from an erythropoiesis-stimulating agent (ESA) (epoetin alfa or darbepoetin alfa) to roxadustat three times/week or to continue their previous ESA. Roxadustat and ESA doses were adjusted to maintain hemoglobin within 10.0-12.0 g/dL during the treatment period (day 1 up to 52--104 weeks). Primary endpoints were hemoglobin change from baseline (CFB) to the average of weeks 28-36 without rescue therapy and hemoglobin CFB to the average of weeks 28-52 regardless of rescue therapy. Treatment-emergent adverse events (TEAEs) were assessed descriptively. Results: Of 1081 screened patients, 836 were randomized and received treatment (roxadustat, n = 415; ESA, n = 421). The least squares means (95% CI) of the treatment difference (roxadustat -ESA) for hemoglobin CFB to weeks 28-36 (without rescue therapy) and CFB to weeks 28-52 (regardless of rescue therapy) were 0.235 (0.132, 0.339) g/dL and 0.171 (0.082, 0.261) g/dL, respectively, demonstrating noninferiority of roxadustat to ESA (non-inferiority margin of -0.75 g/dL). The proportions of patients who achieved target hemoglobin without rescue therapy during weeks 28-36 were 84.2% (roxadustat) and 82.4% (ESA).

SKYLIGHT 4 (Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause) demonstrates the 52-week safety and tolerability of fezolinetant and its use for the treatment of vasomotor symptoms associated with menopause.