A Phase 3, Multicenter, Randomized, Open-Label, Active Comparator Conversion Study of Roxadustat in Non-Dialysis-Dependent (NDD) Patients with Anemia in CKD

Journal of the American Society of Nephrology, vol. 31, pp. 134

Abstract

Background: Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of anemia in CKD. Efficacy and long-term safety of roxadustat was assessed, following conversion from darbepoetin alfa (DA), recombinant human erythropoietin (rHuEPO), or epoetin beta pegol (EBP) to roxadustat, in NDD-CKD patients (pts) with anemia. Noninferiority of roxadustat efficacy against DA was evaluated. Methods: This study enrolled adult Japanese NDD-CKD pts receiving DA, rHuEPO, or EBP for ≥8 weeks before prescreening. Patients who had used rHuEPO or DA were randomized to receive roxadustat or DA (comparative group [CG]). EBP-using pts were allocated to receive roxadustat (referential group [RG]). The primary endpoint was change in average hemoglobin (Hb) from baseline (BL) at Weeks 18-24. Roxadustat efficacy was confirmed if the 95% CI of average Hb at Weeks 18-24 was within 10-12 g/dL; noninferiority of roxadustat to DA was confirmed if the lower limit of the 95% CI of the difference between roxadustat and DA (CGs) was above -0.75 g/dL. Treatment-emergent adverse events (TEAEs) were assessed. Results: A total of 262 pts were randomized to CGs and received ≥1 dose of roxadustat (n=131) or DA (n=131); 70 pts were allocated to RG and received ≥1 dose. The mean (95% CI) of average Hb at Weeks 18-24 in roxadustat (CG) was 11.14 (11.01, 11.27) g/dL, confirming the efficacy of roxadustat. The difference between roxadustat and DA (CGs) in the change in average Hb from BL at Weeks 18-24 was -0.07 g/dL (95% CI: -0.23, 0.10), confirming noninferiority of roxadustat to DA. The incidence of TEAEs observed during the 24-week treatment period was 78.6% in roxadustat (CG), 70.2% in DA (CG), and 77.1% in roxadustat (RG). Common TEAEs included nasopharyngitis, CKD, hyperkalemia, and hypertension; rates of these were comparable between groups. Conclusions: This study confirmed the efficacy of roxadustat after conversion from DA, rHuEPO, or EBP, as well as its noninferiority to DA, in NDD-CKD pts with anemia. The safety profile of roxadustat was consistent with previous reports. A final analysis of this study (including 52-week data) will be presented at the congress. Funding: Commercial Support - Astellas Pharma, Inc.

Authors 4

1. Tadao Akizawa

   SHOWA Medical University

   Affiliation as printed

   Showa University School of Medicine, Tokyo, Japan;

2. Manabu Iwasaki

   Yokohama City University

   Affiliation as printed

   Yokohama City University, Yokohama, Japan;

3. Tetsuro Otsuka

   Astellas Pharma (Japan)

   Affiliation as printed

   Astellas Pharma, Inc., Tokyo, Japan;

4. Yusuke Yamaguchi

   Astellas Pharma (Japan)

   Affiliation as printed

   Astellas Pharma, Inc., Tokyo, Japan;