ROCKIES & OLYMPUS: Roxadustat increases Hb in CKD patients regardless of dialysis status
Roxadustat, an oral hypoxia–inducible factor prolyl hydroxylase inhibitor (HIF-PHI), provides significantly greater increases in mean haemoglobin (Hb) levels from baseline than epoetin alfa and placebo in dialysis-dependent patients and dialysis-independent patients with chronic kidney disease (CKD), respectively, according to late-breaking results of the ROCKIES and OLYMPUS trials presented at the American Society of Nephrology (ASN) Meeting 2019.
The phase III, international, randomized, open-label ROCKIES trial enrolled 2,133 CKD patients (mean age, 54.0 years; 59 percent male) on dialysis to assess the efficacy and safety of thrice-weekly oral roxadustat vs an active control agent, parenteral epoetin alfa. [Fishbane S, et al, ASN 2019, abstract TH-OR022]
Roxadustat met the primary efficacy endpoint of greater Hb change from baseline to average Hb in the overall population in weeks 28 to 52 vs epoetin alfa (adjusted least squares mean [aLSM] change, +0.77 g/dL vs +0.68 g/dL; p=0.036). “Roxadustat also increased Hb to a greater degree than epoetin [aLSM change, 0.80 g/dL vs 0.59 g/dL; p=0.12] in patients with high-sensitivity C-reactive protein [hsCRP] levels over 5 mg/L, who represent a population historically difficult to treat with epoetin,” said first author, Professor Steven Fishbane of Northwell Health, Great Neck, New York, US.
Roxadustat-treated patients saw an aLSM change in serum iron of +6.58 µg/dL, compared with -5.54 µg/dL in the epoetin group. “Average monthly intravenous [IV] iron use was 35 percent lower in patients on roxadustat compared with those on epoetin [59 mg vs 91 mg; p<0.001],” noted Fishbane.
The rate of any reported adverse events (AEs) was 168.2 per 100 patient-years (P-Y) for roxadustat vs 132.5 for epoetin. The rate of any AEs leading to discontinuation was also higher with roxadustat (3.1 per 100 P-Y vs 1.2 per 100 P-Y), as was the rate of any serious AEs (49.2 per 100 P-Y vs 43.5 per 100 P-Y). “However, the rate of all-cause mortality was virtually the same between the two groups [9.0 per 100 P-Y vs 8.9 per 100 P-Y],” reported Fishbane.
In the phase III, international, randomized, double-blind, placebo-controlled OLYMPUS trial, roxadustat met the primary efficacy endpoint of greater Hb change from baseline to average Hb in the overall population in weeks 28 to 52 vs placebo (aLSM change, +1.75 g/dL vs +0.4 g/dL; p<0.001) in dialysis-independent patients. [Fishbane S, et al, ASN 2019, abstract TH-OR023]
“Roxadustat achieved a similarly elevated Hb response vs placebo, regardless of patients’ iron repletion status [iron-replete patients: aLSM change, +1.71 g/dL vs +0.39 g/dL; p<0.01; non-iron—replete patients: aLSM change, +1.76 g/dL vs +0.43 g/dL; p<0.001]. In addition, roxadustat demonstrated comparable efficacy in the traditionally hyporesponsive population of patients with elevated hsCRP [aLSM change, +1.73 g/dL vs 0.62 g/dL],” reported Fishbane.
The need for rescue therapy was significantly reduced with roxadustat vs placebo. “The risk of requiring a red blood cell transfusion decreased by 63 percent in patients on roxadustat [hazard ratio (HR), 0.37; 95 percent confidence interval (CI), 0.30 to 0.44; p<0.001], while the risk of needing IV iron was 59 percent lower in the roxadustat group [HR, 0.41; 95 percent CI, 0.29 to 0.56; p<0.001] and the risk of requiring rescue with an erythropoietin analogue was down by 87 percent [HR, 0.13; 95 percent CI, 010 to 0.18; p<0.001],” said Fishbane.
“The rates of any AE [182.9 per 100 P-Y vs 171.9 per 100 P-Y], AE-related discontinuations [2.8 per 100 P-Y vs 2.1 per 100 P-Y] and any serious AE [SAE, 42.1 per 100 P-Y vs 40.0 per 100 P-Y] were similar between the roxadustat and placebo arms,” said Fishbane. Among the most reported SAEs, which were elevated in the roxadustat group, were sepsis (1.8 per 100 P-Y vs 0.8 per 100 P-Y) and hyperkalaemia (1.5 per 100 P-Y vs 0.9 per 100 P-Y). “However, the rates were quite low in both groups,” noted Fishbane.