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

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.

• Authors: Steven Fishbane, Mohamed A El-Shahawy, Roberto Pecoits-Filho, Bui Pham Van, Mark T Houser, Lars Frison, Dustin J Little, Nicolas J Guzman, Pablo E Pergola
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 32 Issue 3 Pg. 737-755 (03 2021) ISSN: 1533-3450 [Electronic] United States
• PMID: 33568383 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 by the American Society of Nephrology.

Chemical References

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

Topics

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