Kidney Week

Abstract: TH-OR02

Roxadustat for the Treatment of Anemia in CKD Patients Not on Dialysis (NDD): A Phase 3, Randomized, Open-Label, Active-Controlled Study

Session Information

• Breakthroughs in Anemia and Iron Management
  October 22, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom

Jonathan Barratt, MBChB, PhD



I lead the Renal Research Group within the College of Life Sciences, University of Leicester. My research interests span a range of areas across renal medicine and include glomerular disease, multi-system renal disease and complications of chronic kidney disease, in particular renal associated anaemia. I am the IgA nephropathy Rare Disease Group lead for the UK National Registry of Rare Kidney Diseases (RaDaR) and a member of the steering committee for the International IgA Nephropathy Network. I am Chief Investigator for a number of international randomised controlled clinical trials, have attended both the FDA and EMA as an advisor for new therapies in IgA nephropathy, and am a member of the FDA and American Society of Nephrology Kidney Health Initiative: Identifying Surrogate Endpoints for Clinical Trials in IgA Nephropathy Workgroup. I am an Editorial Board member for Kidney International and Clinical Journal of the American Society of Nephrology and sit on the Kidney Research UK Grants Committee.

• Andric, Branislav, Health Center Krusevac, Kruševac, Serbia

Branislav Andric,

• Tataradze, Avtandil, National Center of Urology, Tbilisi, Tbilisi , Georgia

Avtandil Tataradze,

• Schoemig, Michael, Center of Dialysis and Nephrology, Heilbronn and Neckarsulm, Germany

Michael Schoemig,

• Reusch, Michael, Astellas Pharma Europe B.V., Leiden, Netherlands

Michael Reusch,

• Valluri, Udaya, Astellas Pharma Europe B.V., Leiden, Netherlands

Udaya Valluri,

• Mariat, Christopher R., CHU St Etienne, Service Nephrologie Dialyse Transplantation, St Etienne, France

Christopher R. Mariat,

Background

Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor to treat anemia in adult CKD patients (pts). Efficacy and safety of roxadustat versus darbepoetin alfa (DA) were assessed in NDD CKD pts in a randomized, open-label, active-controlled phase 3 study.

Methods

NDD CKD pts with anemia were randomized to roxadustat or DA for up to 2 years. Dose adjustments were permitted to correct and maintain hemoglobin (Hb) within 10–12 g/dL. The primary endpoint was Hb response, defined as Hb ≥11.0 g/dL and Hb increase from baseline (BL) of ≥1.0 g/dL in pts with BL Hb >8.0 g/dL, or an increase of ≥2.0 g/dL in pts with BL Hb ≤8.0 g/dL, during the first 24 weeks of treatment without rescue therapy. Noninferiority of roxadustat to DA was declared if the lower bound of the two-sided 95% confidence interval (CI) for the difference (roxadustat – DA) in proportion of responders was >-0.15. Key secondary endpoints included change in low-density lipoprotein (LDL) cholesterol, time to first IV iron use, change in mean arterial pressure (MAP), and occurrence of hypertension. Treatment-emergent adverse events (TEAEs) were assessed.

Results

Of 616 randomized pts (roxadustat, 323; DA, 293), 424 completed 2 years of treatment (roxadustat, 215; DA, 209). Mean BL Hb was 9.55 g/dL in both groups. In the per protocol set, the proportion of pts who achieved Hb response during the first 24 weeks was 89.5% (roxadustat; n=256/286) and 78.0% (DA; n=213/273), with a difference of 11.51% (95% CI: 5.66%, 17.36%), thereby establishing roxadustat’s noninferiority to DA. Noninferiority of roxadustat to DA was demonstrated for MAP and time to occurrence of hypertension. Superiority of roxadustat to DA was demonstrated for decreasing LDL cholesterol (p<0.001) and increasing time to first IV iron use (p=0.004). The incidence of TEAEs was comparable between roxadustat (91.6%) and DA (92.5%). Common TEAEs in both groups were end-stage renal disease, hypertension, decreased eGFR, and peripheral edema.

Conclusion

Roxadustat was noninferior to DA for Hb response during the first 24 weeks of treatment in NDD CKD pts. Safety profiles were comparable between groups.

Funding

• Commercial Support – Astellas Pharma, Inc.