Abstract: SA-PO228
ANDES: A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat for the Treatment of Anemia in CKD Patients Not on Dialysis
Session Information
- Anemia and Iron Metabolism: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 202 Anemia and Iron Metabolism: Clinical
Authors
- Coyne, Daniel W., Washington University School of Medicine, St. Louis, Missouri, United States
- Roger, Simon D., Renal Research, Gosford, New South Wales, Australia
- Shin, Sug kyun, Ilsan Hospital NHIS, Goyang-si, Korea (the Republic of)
- Kim, Sung gyun, Hallym University, Chuncheon, Korea (the Republic of)
- Cadena, Andres A., Clinica de la Costa, Barranquilla, Colombia
- Moustafa, Moustafa A., South Carolina Nephrology & Hypertension Center, Inc, Orangeburg, South Carolina, United States
- Chan, Daniel Tak Mao, Queen Mary Hospital, Pokfulam, HKSAR, HONG KONG, China
- Chou, Willis, FibroGen, Inc., San Francisco, California, United States
- Bradley, Charles, FibroGen, Inc., San Francisco, California, United States
- Eyassu, Meraf, FibroGen, Inc., San Francisco, California, United States
- Besarab, Anatole, FibroGen, Inc., San Francisco, California, United States
- Leong, Robert, FibroGen, Inc., San Francisco, California, United States
- Lee, Tyson T., FibroGen, Inc., San Francisco, California, United States
- Neff, Thomas B., FibroGen, Inc., San Francisco, California, United States
- Szczech, Lynda, FibroGen, Inc., San Francisco, California, United States
- Yu, Kin-Hung Peony, FibroGen, Inc., San Francisco, California, United States
Background
Roxadustat (FG-4592; ASP1517; AZD9941) is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism.
Methods
In this Ph3, randomized, double-blinded, placebo-controlled trial, the efficacy and safety of roxadustat vs. placebo was evaluated in patients (pt) with anemia and chronic kidney disease (stages 3-5) who were not dialysis-dependent (NDD-CKD). 922 pt were randomized (2:1) to receive oral roxadustat (n=616) or placebo (n=306) three-times weekly based on a tiered, weight-based scheme. Oral iron was allowed, IV iron was withheld except for rescue. Study drug dose was adjusted based on a dosing algorithm to correct and maintain hemoglobin (Hb). Primary efficacy endpoints were change in Hb from baseline (BL) to the average level during weeks (wk) 28-52 (for US [FDA]) and the proportion of subjects who achieve an Hb response at two consecutive visits during the first 24 wk of treatment without rescue therapy (for EU [EMA]). Safety and tolerability were assessed by adverse events, vital signs, ECG findings, and clinical laboratory values.
Results
Mean age was 64.9 years (yr) in the roxadustat arm and 64.8 in the placebo arm. Other BL characteristics were well balanced including BL Hb levels that averaged 9.1 g/dL in both arms. Treatment duration was up to 4.5 yr, with average duration of 1.7 yr. Mean change in Hb from BL to the average over wk 28-52 was 2.00 g/dL for roxadustat vs. 0.16 g/dL for placebo (p<0.0001). The proportion of pt who achieved an Hb response at two consecutive visits during the first 24 wk of treatment was 86.0% for roxadustat vs. 6.6% for placebo (p=0.0007). Roxadustat reduced the risk of rescue therapy by 81% (HR=0.19) and the risk of blood transfusion by 74% (HR = 0.26), both p<0.0001. Pooled safety analysis will be submitted as a late breaking clinical trial abstract.
Conclusion
Roxadustat was superior to placebo in mean Hb change from BL to the average over wk 28-52 with a higher proportion of roxadustat-treated pt achieving an Hb response in the first 24 wk.
Funding
- Commercial Support – Fibrogen Inc.