Kidney Week

Abstract: TH-OR023

OLYMPUS: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, International Study of Roxadustat Efficacy in Patients with Non-Dialysis-Dependent (NDD) CKD and Anemia

Session Information

• Anemia and Iron Metabolism: Clinical Research
  November 07, 2019 | Location: 150, Walter E. Washington Convention Center
  Abstract Time: 04:54 PM - 05:06 PM

Category: Anemia and Iron Metabolism

• 202 Anemia and Iron Metabolism: Clinical

Authors

• Fishbane, Steven, Northwell Health, Great Neck, New York, United States

Steven Fishbane, MD

• El-Shahawy, Mohamed A., Keck-USC School of Medicine, Los Angeles, California, United States

Mohamed A. El-Shahawy,

• Pecoits-Filho, Roberto, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States

Roberto Pecoits-Filho,

• Pham van, Bui, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Viet Nam

Bui Pham van,

• Houser, Mark T., AstraZeneca, Gaithersburg, Maryland, United States

Mark T. Houser,

• Frison, Lars, AstraZeneca, Mölndal, Sweden

Lars Frison,

• Little, Dustin J., AstraZeneca, Gaithersburg, Maryland, United States

Dustin J. Little,

• Guzman, Nicolas Jose, AstraZeneca, Gaithersburg, Maryland, United States

Nicolas Jose Guzman,

• Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States

Pablo E. Pergola,

Background

Roxadustat is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron absorption and utilization. Here, we report efficacy results for 1 of 3 trials for US and EU applications for treatment of anemia in patients (pts) with NDD CKD. Integrated safety will be reported separately.

Methods

Pts with NDD CKD stages 3–5 and anemia (hemoglobin [Hb] <10.0 g/dL) were randomized 1:1 to receive 70 mg oral roxadustat or placebo (PBO) three times weekly. A dose-adjustment algorithm was used to achieve and maintain Hb values of 10–12 g/dL. Primary efficacy endpoint was mean change from baseline (BL) Hb to average Hb over Wks 28–52 (US [FDA] submission) or proportion of pts with Hb response at two consecutive visits during the first 24 wks of treatment without anemia rescue therapy (EU [EMA] submission).

Results

2781 pts were randomized (1393 roxadustat, 1388 PBO). Mean age was 61.7 years, 42% were male, 45% white, and 55% had type 2 diabetes. Mean (SD) BL Hb was 9.1 (0.7) g/dL and estimated glomerular filtration rate was 19.8 (11.7) mL/min/1.73 m². Mean (SD) study drug exposure was 19.6 (10.3; roxadustat) and 15.2 (10.5; PBO) months. Mean change in Hb from BL to the average over Wks 28–52 was +1.75 g/dL with roxadustat vs +0.40 g/dL with PBO (p<0.001). In 411 pts with BL elevated high-sensitivity C-reactive protein (hsCRP), changes from BL Hb were +1.75 g/dL (roxadustat) and +0.62 g/dL (PBO; p<0.001). Proportion of pts achieving Hb response at two consecutive visits without rescue during the first 24 wks was 77.0% with roxadustat vs 8.5% with PBO (p<0.001). Percentage of total time with interpolated Hb values ≥10 g/dL for Wks 28–52 was 82% with roxadustat vs 33% with PBO (p<0.001). Roxadustat reduced risk of rescue therapy by 74% (HR=0.26), including red blood cell transfusion by 63% (HR=0.37), IV iron by 59% (HR=0.41), and erythropoietin analog by 87% (HR=0.13; all p<0.001).

Conclusion

Roxadustat achieved prespecified primary endpoints for US and EU submissions, effectively increased Hb in the subgroup of pts with elevated hsCRP, and reduced rescue therapy use in pts with NDD CKD and anemia.

Funding

• Commercial Support –