Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis

N Engl J Med. 2019 Sep 12;381(11):1001-1010. doi: 10.1056/NEJMoa1813599. Epub 2019 Jul 24.

Abstract

Background: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis.

Methods: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9.

Results: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period.

Conclusions: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).

Publication types

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

MeSH terms

  • Acidosis / chemically induced
  • Adult
  • Aged
  • Anemia / drug therapy*
  • Anemia / etiology
  • Cholesterol / blood
  • Double-Blind Method
  • Female
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Glycine / therapeutic use
  • Hematinics / adverse effects
  • Hematinics / therapeutic use
  • Hemoglobins / analysis*
  • Humans
  • Hyperkalemia / chemically induced
  • Hypoxia-Inducible Factor-Proline Dioxygenases / antagonists & inhibitors*
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*

Substances

  • FG-4592
  • Hematinics
  • Hemoglobins
  • Isoquinolines
  • Cholesterol
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Glycine

Associated data

  • ClinicalTrials.gov/NCT02652819