• Chen N, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med 2019; doi: 10.1056/NEJMoa1813599;

  • Chen N, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med 2019; doi: 10.1056/NEJMoa1901713.

Roxadustat for Anemia: New Trials in Dialysis and Nondialysis Patients

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Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is an effective treatment for anemia both in nondialysis patients with chronic kidney disease (CKD) and in long-term dialysis patients, according to a pair of industry-sponsored trials recently published in the New England Journal of Medicine (NEJM).

Nondialysis trial

The nondialysis CKD trial included 154 patients who were enrolled at 29 sites in China. All the patients with CKD had baseline hemoglobin levels of 7.0 to less than 10 g/dL. None of the patients had received erythropoiesis-stimulating agents for at least the previous 5 weeks.

The researchers note that in China, patients typically have low hemoglobin levels at the time they initiate dialysis. Only about half of patients achieve a hemoglobin level of 10.0 g/dL or higher with the use of recombinant erythropoietin therapy.

In the NEJM study, patients were randomly assigned to 8 weeks of treatment with roxadustat or placebo according to a 2:1 ratio. Roxadustat was started at a dose of 70 or 100 mg and adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The average change in hemoglobin level from week 7 through week 9 was compared between the two groups of patients. The investigators found that during this period, hemoglobin increased by 1.9 g/dL with roxadustat, compared with a 0.4 g/dL decrease in the placebo group.

Roxadustat was also found to be associated with larger reductions in hepcidin, reflecting greater iron availability in the patients taking the drug. The mean reductions in hepcidin were 56.14 ng/mL in patients assigned to roxadustat, compared with 15.10 ng/mL in the placebo group, amounting to a between-group difference of −49.77 ng/mL. Roxadustat was also associated with a greater reduction in mean total cholesterol level between the two groups of patients, with a between-group difference of −21.2 mg/dL.

With regard to side effects, patients receiving roxadustat were more likely to experience hyperkalemia and metabolic acidosis than were patients in the placebo group. The increase in hemoglobin levels and continued maintenance of those hemoglobin levels persisted during an 18-week, open-label period in which all patients received roxadustat.

Dialysis trial

The dialysis trial included 305 long-term dialysis patients in China. The mean baseline hemoglobin for these patients was 10.4 g/dL, and all patients had been receiving erythropoietin-α for at least 6 weeks. In a 2:1 ratio, patients were randomly assigned to 26 weeks of treatment with roxadustat or with erythropoietin-α.

Roxadustat was associated with a numerically greater increase in hemoglobin: 0.5 versus 0.7 g/dL. The difference of less than 1.0 g/dL demonstrated the noninferiority of roxadustat. Patients receiving roxadustat had an increased transferrin level, continued maintenance of serum iron level, and a lesser decrease in transferrin saturation, compared with the patients not receiving roxadustat. As was the case in the nondialysis CKD trial, the roxadustat group had greater reductions in hepcidin and total cholesterol. Roxadustat was associated with higher rates of hyperkalemia and respiratory infections, and erythropoietin-α was associated with a higher rate of hypertension.

Together, the two studies show that roxadustat is superior to placebo in correcting anemia in nondialysis CKD patients and that roxadustat is noninferior to erythropoietin-α for treatment of anemia in long-term dialysis patients. The authors highlight the need for long-term safety data.

Results from a larger trial are expected soon, with MACE (Major Adverse Cardiovascular Events) data on Roxadustat for CKD-related anemia in 9000+ patients with nondialysis and dialysis CKD.

  • Chen N, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med 2019; doi: 10.1056/NEJMoa1813599;

  • Chen N, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med 2019; doi: 10.1056/NEJMoa1901713.

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