Roxadustat Treatment Results in Consistent Improvements in Hemoglobin (Hb) Versus Placebo: An Analysis of 3 Multinational RCTs in Patients with Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD)

Background: Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin and enhances iron utilization. To evaluate the consistency of Hb increases across studies and global geographic regions, we analyzed data from three pivotal Phase 3 trials of roxadustat in patients with anemia and NDD-CKD.

Methods: While based on the same trial design, the studies were performed by different investigators and companies in differing global regions. Patients with baseline Hb <10 g/dL and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² not on dialysis were randomized to roxadustat or placebo (pbo) in the OLYMPUS (North and South America, Asia-Pacific and Europe; N=2781, 1:1 ratio to pbo), ALPS (South America, Europe and South Africa; N=597, 2:1 ratio to pbo), and ANDES (North and South America, Asia-Pacific and Australasia; N=922; 2:1 ratio to pbo) double-blind randomized controlled trials (RCTs). Oral iron was administered unrestricted; intravenous (IV) iron was limited to rescue therapy in those with low iron stores and poor treatment response. The primary endpoint was the mean change in Hb from baseline to the average over Weeks 28–52.

Results: Significant (P<0.001) and consistent improvements in Hb were observed with roxadustat vs pbo across all studies (Figure) and were maintained over time. IV iron rescue therapy use was lower with roxadustat vs pbo (Figure). Overall safety of roxadustat was comparable with pbo and consistent with the CKD patient population.

Conclusion: Roxadustat consistently improved anemia in patients with NDD-CKD across the global roxadustat clinical program, in studies performed by different investigators and companies and in varying global locations.