Roxadustat was more effective than placebo at increasing haemoglobin in patients with non–dialysis-dependent chronic kidney disease (CKD) and anaemia, while decreasing transfusion rate, found a US phase III trial.
Many people with kidney dysfunction develop anaemia. Some treatments are linked with serious cardiovascular side effects, but a new class of oral drugs called hypoxia inducible factor-prolyl hydroxylase inhibitors may be comparable to placebo in these trials. These drugs act on the pathway involved in the production of erythropoietin that stimulates red blood cell formation.
To evaluate the efficacy and cardiovascular safety of one such inhibitor – called roxadustat – Dr Robert Provenzano (Wayne State University School of Medicine) and his colleagues analysed data pooled from three phase 3 studies of roxadustat in patients with chronic kidney disease and anaemia.
The study was published in the Clinical Journal of the American Society of Nephrology.
In total, 2,391 patients received roxadustat and 1,886 received a placebo. Roxadustat treatment boosted levels of haemoglobin (the protein in red blood cells responsible for transporting oxygen): roxadustat- vs. placebo- treated patients showed an average change in haemoglobin averaged over weeks 28 to 52 of 1.9 vs. 0.1 g/dL. Roxadustat also reduced the need for red blood cell transfusions in the first 52 weeks, and there were no increased risks of mortality, heart attacks, strokes linked to the drug.
"Roxadustat was shown to be effective, with an acceptable safety profile," said Provenzano. "As an oral agent, roxadustat addresses the significant unmet need in treating anaemia in patients with kidney disease."
Study details
Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non–Dialysis-Dependent CKD
Pooled Results of Three Randomized Clinical Trials
Robert Provenzano, Lynda Szczech, Robert Leong, Khalil G. Saikali, Ming Zhong, Tyson T. Lee, Dustin J. Little, Mark T. Houser, Lars Frison, John Houghton and Thomas B. Neff
Published in Clinical Journal of the American Society of Nephrology in August 2021
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 m2. 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 haemoglobin in patients with non–dialysis-dependent CKD and anaemia, while decreasing transfusion rate and being noninferior to placebo with respect to risk of MACE.
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