Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 Study

J Am Soc Nephrol. 2021 Mar;32(3):737-755. doi: 10.1681/ASN.2020081150. Epub 2021 Feb 10.

Abstract

Background: Current anemia therapies for patients with non-dialysis-dependent CKD may require injection and medical visits. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis and improves iron homeostasis.

Methods: In this double-blind phase 3 study, we randomized patients with non-dialysis-dependent CKD stages 3-5 and hemoglobin <10.0 g/dl (1:1) to thrice-weekly 70-mg oral roxadustat or placebo. Doses were titrated throughout the study based on hemoglobin levels. The primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52 versus placebo, irrespective of rescue therapy use. We assessed patients for adverse events.

Results: The study included 2781 patients, 1393 who received roxadustat and 1388 who received placebo. Mean baseline hemoglobin was 9.1 g/dl for both groups. The mean change in hemoglobin from baseline was 1.75 g/dl (95% confidence interval [95% CI], 1.68 to 1.81) with roxadustat versus 0.40 g/dl (95% CI, 0.33 to 0.47) with placebo, (P<0.001). Among 411 patients with baseline elevated high-sensitivity C-reactive protein, mean change in hemoglobin from baseline was 1.75 g/dl (95% CI, 1.58 to 1.92) with roxadustat versus 0.62 g/dl (95% CI, 0.44 to 0.80) with placebo, (P<0.001). Roxadustat reduced the risk of red blood cell transfusion by 63% (hazard ratio, 0.37; 95% CI, 0.30 to 0.44). The most common adverse events with roxadustat and placebo, respectively, were ESKD (21.0% versus 20.5%), urinary tract infection (12.8% versus 8.0%), pneumonia (11.9% versus 9.4%), and hypertension (11.5% versus 9.1%).

Conclusions: Roxadustat effectively increased hemoglobin in patients with non-dialysis-dependent CKD and reduced the need for red blood cell transfusion, with an adverse event profile comparable to that of placebo.

Clinical trial registry name and registration number: Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With CKD, Not on Dialysis, NCT02174627.

Keywords: anemia; chronic kidney disease; clinical nephrology; clinical trial; randomized controlled trials.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anemia / blood
  • Anemia / drug therapy*
  • Anemia / etiology*
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Glycine / therapeutic use
  • Hematinics / adverse effects
  • Hematinics / therapeutic use*
  • Hemoglobins / metabolism
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases / antagonists & inhibitors
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Male
  • Middle Aged
  • Prolyl-Hydroxylase Inhibitors / adverse effects
  • Prolyl-Hydroxylase Inhibitors / therapeutic use*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / drug therapy*
  • Safety

Substances

  • Hematinics
  • Hemoglobins
  • Isoquinolines
  • Prolyl-Hydroxylase Inhibitors
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Glycine
  • roxadustat

Associated data

  • ClinicalTrials.gov/NCT02174627