Kidney Week

Abstract: TH-OR022

ROCKIES: An International, Phase 3, Randomized, Open-Label, Active-Controlled Study of Roxadustat for Anemia in Dialysis-Dependent CKD Patients

Session Information

• Anemia and Iron Metabolism: Clinical Research
  November 07, 2019 | Location: 150, Walter E. Washington Convention Center
  Abstract Time: 04:42 PM - 04:54 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

• Pollock, Carol A., The University of Sydney, Sydney, New South Wales, Australia

Carol A. Pollock,

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

Mohamed A. El-Shahawy,

• Escudero, Elizabeth Teresa, Hospital Arzobispo Loayza, Lima, Peru

Elizabeth Teresa Escudero,

• Rastogi, Anjay, University of California Los Angeles, Los Angeles, California, United States

Anjay Rastogi,

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

Bui Pham van,

• Frison, Lars, AstraZeneca, Mölndal, Sweden

Lars Frison,

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

Mark T. Houser,

• Pola, Maksym, AstraZeneca, Warsaw, Poland

Maksym Pola,

• 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.

Methods

This Phase 3 trial evaluated roxadustat vs epoetin alfa (epo) in patients (pts) with ESRD and anemia receiving dialysis. Pts with baseline (BL) hemoglobin (Hb) of <12 g/dL if treated with an erythropoietin analog or <10 g/dL if not were recruited. Pts were randomized 1:1 to receive oral roxadustat or epo. For pts receiving epo at BL, initial roxadustat dose was based on epo dose; for epo-naïve pts initial roxadustat dose was weight-based. Roxadustat dose was constant for first 4 wks; a dose adjustment algorithm for roxadustat (20 mg qw–400 mg tiw to max 3 mg/kg) was used to maintain Hb between 10–12 g/dL. Oral iron was allowed; IV iron was used as standard-of-care in epo arm and with evidence of iron deficiency in roxadustat arm. Primary efficacy endpoint was mean Hb change from BL to Hb averaged over wks 28–52. Roxadustat safety data integrated across multiple appropriate dialysis trials will be reported separately.

Results

2133 dialysis pts were randomized (1068 roxadustat, 1065 epo). Mean age was 54.0 years, 59% male, 57% white. Mean duration of dialysis was 37.5 months, 19.5% were incident pts (2 wks to 4 months). Mean (SD) BL Hb was 10.01 (1.22) g/dL. Mean Hb change from BL to average over wks 28–52 was higher with roxadustat (+0.77 g/dL) vs epo (+0.68 g/dL; p=0.036) in the overall cohort. Mean Hb change from BL to average over wks 28–52 in pts with elevated BL high-sensitivity C-reactive protein (hsCRP) was greater with roxadustat (+0.80 g/dL) vs epo (+0.59 g/dL; p=0.012). Roxadustat-treated pts had Hb ≥10 g/dL for a similar proportion of time over wks 28–52 vs epo-treated pts (79% vs 76%, respectively; p=0.045). Proportion of pts who received red blood cell transfusion was comparable between roxadustat and epo arms (HR=0.83; 95% CI: 0.64–1.07). Roxadustat-treated pts used less monthly IV iron from wk 36 to end of study (58.7 vs 91.4 mg, respectively; p<0.0001).

Conclusion

Roxadustat effectively increased Hb, overall and in pts with elevated hsCRP, and reduced IV iron use in pts with dialysis-dependent CKD.

Funding

• Commercial Support –