Roxadustat Safe and Effective in Pooled Results

Analyses of pooled results of phase 3 studies of roxadustat for the treatment of anemia in patients with chronic kidney disease (CKD), including dialysis-dependent patients and nondialysis-dependent patients, were reported in a late breaker session at Kidney Week 2019. Robert Provenzano, MD, FACP, FASN, and Steven Fishbane, MD, reported the data during an oral presentation titled Pooled Efficacy and Cardiovascular (CV) Analyses of Roxadustat in the Treatment of Anemia in Patients on and Not on Dialysis. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that regulates erythropoiesis and iron metabolism.

Results of phase 3 studies comparing roxadustat to placebo in patients with stage 3-5 non­–dialysis-dependent CKD and to epoetin alfa in patients with dialysis-dependent CKD were pooled. Death, myocardial infarction, and stroke (MACE), and heart failure or unstable angina requiring hospitalization (MACE+) were adjudicated. Assessments of efficacy included hemoglobin and the need for rescue therapy (transfusion, intravenous iron, and erythropoiesis stimulating agents). Cardiovascular end points were MACE and MACE+.

In the nondialysis-dependent cohort, 4270 patients were randomized to roxadustat (n=2386) or placebo (n=1884). The primary end point of interest (change from baseline in mean hemoglobin in weeks 28 to 52) was +1.85 g/dL in the roxadustat arm versus 0.13 g/dL in the placebo arm (P<.0001). Patients in the roxadustat had a lower risk of rescue therapy compared with patients in the placebo arm (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.16-0.23; 81% reduction in risk; P<.0001). Using intent-to-treat long-term follow-up, the HR for time to MACE was 1.08 (95% CI, 0.94-1.24) for patients in the roxadustat arm versus placebo. Time to MACE+ was 1.04 (95% CI, 0.81-1.12) in the roxadustat arm versus the placebo arm. In a subgroup with estimated glomerular filtration rate >10 mL/min/1.73 m2 (n=3431), the HRs were 0.99 for MACE and 0.98 for MACE+ for roxadustat versus placebo.

In the dialysis-dependent cohort, 3917 patients were randomized (n=roxadustat, 1960; epoetin alfa, 1957). In the roxadustat arm, the primary end point of mean hemoglobin change from baseline at weeks 28 through 52 was 1.21 g/dL versus 0.95 g/dL in the epoetin alfa arm. (difference, 0.26 g/dL; 95% CI, 0.20-0.33) in pooled analysis. Roxadustat was noninferior and superior to epoetin alfa (P<.0001). Patients in the roxadustat arm received fewer transfusions compared with patients in the epoetin alfa arm: 9.5% versus 12.8% (HR, 0.82; 95% CI, 0.679-0.997).

In comparisons of roxadustat and epoetin alfa, the HR for MACE was 0.95 (95% CI, 0.81-1.12); the HR for MACE+ was 0.84 (95% CI, 0.73-0.97), P=.02) in the dialysis dependent cohort. In a subgroup of incident dialysis patients (dialysis vintage <4 months), the HRs for MACE and MACE+ were 0.70 (95% CI, 0.51-0.97; P=.03) and 0.66 (95% CI, 0.50-0.89; P=.005).

In conclusion, the researchers said, “These integrated Phase 3 analyses provide evidence for roxadustat superiority in anemia correction with transfusion reduction and acceptable cardiovascular safety profile.”

Source: Provenzano R, Fishbane S, Wei L-J, et al. Pooled efficiency and cardiovascular (CV) analyses of roxadustat in the treatment of anemia in CKD patients on and not on dialysis. Abstract of an late-breaker oral presentation at the American Society of Nephrology Kidney Week 2019 (Abstract FR-OR131), November 8, 2019, Washington, DC.