Roxadustat Superior to Epoetin Alfa in Patients With Anemia and Dialysis-Dependent Chronic Kidney Disease

In patients with anemia and dialysis-dependent chronic kidney disease (CKD), treatment with roxadustat led to higher hemoglobin (Hb) levels and a reduced need for red blood cell (RBC) transfusions, compared with treatment with epoetin alfa (EPO), according to research conducted by Steven Fishbane, MD, of the Feinstein Institutes for Medical Research at Northwell Health in New York and presented as part of the 2020 ASH Annual Meeting.

The investigators also found that roxadustat reduced the risk of major adverse cardiovascular events (MACE), including death, myocardial infarction, and stroke, in patients who were enrolled within four months of beginning dialysis.

Erythropoiesis-stimulating agents (ESAs) such as EPO are the current standards of care for anemia in patients with CKD who are on dialysis, with or without intravenous iron supplementation and RBC transfusion. However, because of potential cardiotoxicity associated with ESAs, patients may receive less-than-optimal doses, leading to increased need for RBC transfusions, researchers explained.

Roxadustat is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that regulates erythropoiesis and iron metabolism. To compare the efficacy of this newer agent with the EPO standard-of-care, the investigators conducted a pooled analysis of three phase III trials, the global ROCKIES and HIMALAYAS trials and the U.S.-only SIERRAS trial, each of which evaluated the safety and efficacy of roxadustat against EPO.

Across the trials, a total of 3,890 patients requiring dialysis and anemia treatment were randomized to either roxadustat (n=1,943) or EPO (n=1,947). Mean ages were 54.3 years in the roxadustat group and 55.2 years in the EPO group. Mean baseline Hb levels were similar in each arm (9.6 and 9.7 g/dL).

In the pooled analysis, the primary endpoint (defined as the average change in Hb from baseline to weeks 28-52) was met in each individual study, with roxadustat either performing as noninferior or superior to EPO. In the pooled analysis, the mean change in Hb from baseline was 1.22 g/dL in patients receiving roxadustat, compared with 0.99 g/dL in patients randomized to EPO (p<0.001).

Patients who received roxadustat also received fewer transfusions than those in the EPO group: 9.5% versus 12.8%, respectively (hazard ratio [HR] = 0.82; p=0.997).

Roxadustat also was effective regardless of patients’ inflammation status (determined by elevated C-reactive protein levels). Mean Hb increases in this subset of patients were 1.27 g/dL in the roxadustat group versus 1.05 g/dL in the EPO group (p<0.001).

To review the cardiovascular safety of roxadustat with EPO, the authors reviewed time to first MACE and MACE plus heart failure or unstable angina requiring hospitalization. Comparing roxadustat with EPO, rates of MACE were similar between the treatment arms (HR=0.96); a similar relationship was observed for MACE plus other cardiovascular events (HR=0.86).

The researchers also looked at outcomes in 1,526 patients who had been on dialysis for less than four months and found that patients who received roxadustat had a 30% lower risk of MACE and a 34% lower risk of MACE plus other cardiovascular events.

According to these safety and efficacy findings, roxadustat could offer a new oral treatment option for patients living with CKD and anemia, the researchers concluded.

Study authors report relationships with FibroGen and AstraZeneca, which sponsored this trial.

Reference

Fishbane S, Provenzano R, Szczech L, et al. Pooled Efficacy and Cardiovascular Safety Results of Roxadustat Compared with Epoetin Alfa in the Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis. Abstract #749. Presented at the 2020 American Society of Hematology Annual Meeting, December 5, 2020.