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

ABSTRACT:

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.

SUBMITTER: Shutov E 

PROVIDER: S-EPMC8397511 | biostudies-literature |

REPOSITORIES: biostudies-literature