Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS)

Background. Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of chronic kidney disease (CKD) anemia. Methods. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with Stages 3-5 CKD, not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52-104weeks. This study examined two primary efficacy endpoints: European Union (European Medicines Agency)-hemoglobin (Hb) response, defined as Hb >= 11.0g/dL that increased from baseline (BL) by >= 1.0g/dL in patients with Hb>8.0g/dL or >= 2.0g/dL in patients with BL Hb <= 8.0g/dL, without rescue therapy, during the first 24weeks of treatment; US Food and Drug Administration-change in Hb from BL 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% confidence interval (CI) 20.48-58.93] and change in Hb from BL [roxadustat - placebo: +1.692 (95% CI 1.52-1.86); both P<0.001]. Superiority of roxadustat was demonstrated for low-density lipoprotein cholesterol change from BL, 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 in terms of both Hb response rate and change in Hb from BL. The safety profiles of roxadustat and placebo were comparable.

Automated summary

The study demonstrated that Roxadustat is more effective than placebo in treating anemia in patients with chronic kidney disease. The treatment group showed significantly higher Hb response rate and Hb change from baseline compared to the placebo group.