Abstract: SA-PO227
SIERRAS: A Phase 3, Open-Label, Randomized, Active-Controlled Study of the Efficacy and Safety of Roxadustat in the Maintenance Treatment of Anemia in Subjects with ESRD on Stable 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
- Charytan, Chaim, Nephrology Associates, PC, New Rochelle, New York, United States
- Manllo-Karim, Roberto, South Texas Kidney Specialists, P.A., McAllen, Texas, United States
- Martin, Edouard R., South Florida Nephrology Associates, Lauderdale Lakes, Florida, United States
- Steer, Dylan, Balboa Nephrology Medical Group, La Jolla, California, United States
- Bernardo, Marializa, Southwest Nephrology Associates, Houston, Texas, United States
- Dua, Sohan L., Valley Renal Medical Group, Northridge, California, United States
- Moustafa, Moustafa A., South Carolina Nephrology & Hypertension Center, Inc, Orangeburg, South Carolina, United States
- Saha, Gopal, 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
- Leong, Robert, FibroGen, Inc., San Francisco, California, United States
- Liu, Cameron S., 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) is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism.
Methods
Dialysis patients (pts) were randomized (1:1) to roxadustat (ROXA) or epoetin alfa (EPO). Oral iron was allowed; parenteral iron was restricted. ROXA was dosed thrice weekly. The initial ROXA dose was based on the pts’ preceeding EPO dose. EPO was prescribed according to US Package Insert. An algorithm guided ROXA doses required to maintain Hb. The primary endpoint for US FDA was mean Hb change from baseline (BL) for Weeks (Wks) 28-52; the primary endpoint for the EU EMA submission was mean Hb change from BL to Wks 28-36. Safety and tolerability were assessed by adverse events, vital signs, electrocardiogram findings, and clinical laboratories.
Results
741 pts (370=ROXA, 371=EPO) were randomized. The ROXA-treated pts were 44.6% Caucasian and 42.7% Black while the EPO-treated pts were 49.6% Caucasian and 42.0% Black. The percentage of pts with type-2 DM in the ROXA arm was 65.1% (n=241) and 65.8% (n=244) in the EPO arm. The mean Hb change from BL to the average over Wks 28-52 was 0.39 (ROXA) vs. -0.09 g/dL (EPO). The lower 95% CI for this difference was above the non-inferiority margin of 0.75 g/dL, and met the US criterion for superiority of ROXA over EPO (p<.0001). The mean Hb change from BL to the average over Wks 28-36 was 0.54 (ROXA) vs. -0.02 g/dL (EPO). ROXA met the non-inferiority criteria as the lower bound of 95% CI was above the non-inferiority margin of 0.75 g/dL compared with ESA. ROXA also achieved superiority, p<.0001. ROXA reduced RBC/blood transfusion risk by 33% compared with EPO (HR .67, p<.0037). The overall safety profile was consistent with results observed in prior ROXA trials and pooled safety findings will be submitted as a late breaker abstract.
Conclusion
ROXA was non-inferior and subsequently demonstrated superiority over EPO in the mean change in Hb from BL and in the rate of blood transfusions in dialysis pts.
Funding
- Commercial Support – Fibrogen Inc.