Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD: Pooled Results of Three Randomized Clinical Trials

Department of Internal Medicine, Wayne State University, Detroit, Michigan provenzanorobert5@gmail.com. FibroGen, Inc., San Francisco, California. AstraZeneca, Gaithersburg, Maryland. AstraZeneca, Mölndal, Sweden. Deceased.

Clinical journal of the American Society of Nephrology : CJASN. 2021;16(8):1190-1200
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PICO Summary

Population

Patients with non–dialysis-dependent chronic kidney disease (CKD) and CKD-related anaemia from the three trials: ALPS, ANDES, and OLYMPUS (n= 4,277).

Intervention

Roxadustat (n= 2,391).

Comparison

Placebo (n= 1,886).

Outcome

Patients treated with roxadustat versus those treated with placebo showed a mean change from baseline in haemoglobin averaged over weeks 28-52, regardless of rescue therapy, of 1.9 versus 0.2 g/dl, a treatment difference of 1.7. Roxadustat reduced the need for red blood cell transfusion in the first 52 weeks versus placebo (6.1 versus 20.4 per 100 patient-exposure years, respectively). There were no increased risks on the measures of major adverse cardiovascular events (MACE), MACE and unstable angina and heart failure requiring hospitalization (MACE+), all-cause mortality, or individual MACE+ components in patients treated with roxadustat versus those treated with placebo.
Abstract
BACKGROUND AND OBJECTIVES We evaluated the efficacy and cardiovascular safety of roxadustat versus placebo by analyzing data pooled from three phase 3 studies of roxadustat in patients with non-dialysis-dependent CKD and CKD-related anemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In the three phase 3, double-blind studies of roxadustat versus placebo evaluating the treatment of CKD-related anemia in patients not requiring dialysis, the primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy. The primary cardiovascular safety end point was a composite measure of major adverse cardiovascular events (MACE; all-cause mortality, myocardial infarction, stroke). MACE plus (MACE+; MACE plus unstable angina and heart failure requiring hospitalization) and all-cause mortality were key secondary safety end points. These safety end points were adjudicated. RESULTS A total of 4277 patients with non-dialysis-dependent CKD were randomized (roxadustat, n=2391; placebo, n=1886). Baseline characteristics were comparable between groups; the mean (SD) hemoglobin was 9.1 (0.7) g/dl and mean eGFR was 20 (12) ml/min per 1.73 m(2). Patients treated with roxadustat versus those treated with placebo showed a mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy, of 1.9 versus 0.2 g/dl, a treatment difference of 1.7 (95% confidence interval [95% CI], 1.7 to 1.8). Roxadustat reduced the need for red blood cell transfusion in the first 52 weeks versus placebo (6.1 versus 20.4 per 100 patient-exposure years, respectively; hazard ratio [HR], 0.26; 95% CI, 0.21 to 0.32). There were no increased risks of MACE (HR, 1.10; 95% CI, 0.96 to 1.27), MACE+ (HR, 1.07; 95% CI, 0.94 to 1.21), all-cause mortality (HR, 1.08; 95% CI, 0.93 to 1.26), or individual MACE+ components in patients treated with roxadustat versus those treated with placebo. CONCLUSIONS Roxadustat was more effective than placebo at increasing hemoglobin in patients with non-dialysis-dependent CKD and anemia, while decreasing transfusion rate and being noninferior to placebo with respect to risk of MACE. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER A Study of FG-4592 for the Treatment of Anemia in Chronic Kidney Disease Patients Not Receiving Dialysis, NCT01750190; Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis (ALPS), NCT01887600; Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis, NCT02174627.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine