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March 30, 2020
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Roxadustat effective in patients with CKD even with iron depletion

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Robert Provenzano

In clinical trials, patients with nondialysis-dependent chronic kidney disease using the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat saw an increase in hemoglobin levels regardless of their iron status, according to an abstract presented at the virtual National Kidney Foundation Spring Clinical Meetings.

Robert Provenzano, MD, and investigators reviewed data from the Olympus, Andes and Alps phase 3 studies and a pooled study to determine the efficacy of roxadustat in patients with iron repletion or depletion at baseline. Patients were randomized to roxadustat or placebo for up to 4 years.

Baseline hemoglobin (Hb) levels were recorded overall and for patients with iron repletion (defined as ferritin 100 g/L and transferrin saturation 20%). The remaining patients in the study group were defined as iron depleted. Oral iron was allowed in the study and IV iron was allowed as the rescue therapy.

During the phase 3 studies, 2,391 NDD-CKD patients were treated with roxadustat and 1,886 patients were treated with placebo. Mean hemoglobin was 9.10 (0.74) g/dL for the roxadustat group and 9.10 (0.73) g/dL for the placebo group. At baseline, 1,433 (60%) patients were iron replete and were on roxadustat and 1,127 (60%) patients were iron replete on placebo.

The level of iron depletion in the study group was expected, Provenzano told Healio Nephrology.

“Approximately 90% of ESRD patients require iron supplementation if receiving [erythropoiesis-stimulating agents] ESAs,” he said. “In these trials, nephrologists were allowed to replace iron based on ‘local standards of care.’ Given that this was a global trial these numbers are not surprising.”

The results of the data review showed that, regardless of iron status, patients in the three study groups saw Hb levels increase between 1.75 g/dL to 2.02 g/dL.

“The results showed that the change from baseline was similar in iron-replete and depleted patients receiving roxadustat,” the authors wrote.

Provenzano said while the results were positive, iron therapy will still play an important role with hypoxia-inducible factor prolyl hydroxylase inhibitors.

“It does appear that iron requirements will be significantly less and could be met with oral rather than IV replacement,” he said. – by Mark E. Neumann

Reference: Provenzano R, et al. Abstract #192. Presented at: National Kidney Foundation Spring Clinical Meetings; March 26-29, 2020 (virtual meeting).

Disclosure: Provenzano reports he is a principle investigator for Astra Zeneca.