Abstract: TH-OR021
HIMALAYAS: A Phase 3, Randomized, Open-Label, Active-Controlled Study of the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Incident-Dialysis Patients
Session Information
- Anemia and Iron Metabolism: Clinical Research
November 07, 2019 | Location: 150, Walter E. Washington Convention Center
Abstract Time: 04:30 PM - 04:42 PM
Category: Anemia and Iron Metabolism
- 202 Anemia and Iron Metabolism: Clinical
Authors
- Provenzano, Robert, DaVita Healthcare, Denver, Colorado, United States
- Evgeny, Shutov, Botkins hospital, Moscow, Russian Federation
- Liubov, Eremeeva, LLC Fresenius Medical Care Kuban, Krasnodar, Russian Federation
- Korneyeva, Svitlana, Zaporizhzhia regional clinical hospital, Zaporizhzhia, Ukraine
- Kathresal, Amarnath A., Durham Nephrology Associates, Cary, North Carolina, United States
- Poole, Lona, FibroGen, Inc., San Francisco, California, 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
- Besarab, Anatole, 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
- 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) is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism.
Methods
ESA-naïve or limited prior use, incident dialysis pts were randomized (1:1) to roxadustat (ROXA) or epoetin alfa (EPO) . Oral iron was allowed;parenteral iron was restricted. Oral ROXA was dosed thrice weekly. The initial roxadustat dose was weight-based. EPO was prescribed according to the country-specific product labeling. An algorithm determined ROXA doses. The primary endpoint for the US FDA was mean Hb change from baseline (BL) to Weeks (Wk) 28-52. The primary endpoint for EU EMA was the % of pts achieving a Hb response through Wk 1-24. An Hb response was defined at 2 consecutive visits during the first 24 Wk as achieving a Hb level of 11 and an increase of 1 g/dL if BL Hb was >8 gor 2 g/dL if baseline Hb was <8 g/dL. Safety and tolerability were assessed by adverse events, vital signs, electrocardiogram findings, and clinical laboratory values.
Results
1,043 pts (522=ROXA, 521=EPO) ≥18 years old were randomized in 17 countries. Pts were majority Caucasian with 8.4% Black pts in the ROXA arm and 9.6% Black pts in the EPO arm. The % of pts with type 2 DM in the ROXA arm was 35.1% (n=183) and 34.4% (n=179) in the EPO arm. Mean BL Hb was 8.43 g/dL in the ROXA arm and 8.46 g/dL in the EPO arm. Mean Hb change from BL to the average over Wk 28-52 was 2.57 (ROXA) vs. 2.36 g/dL (EPO). The non-inferiority criteria were met as the lower bound of 95% CI was above the non-inferiority margin of -0.75 g/dL, and superiority over EPO was also achieved, p=.0005. ROXA pts had an Hb response rate of 88.2% compared with 84.4% in the EPO arm meeting EU’s primary endpoint non-inferiority criterion. 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 in pts incident to dialysis.
Funding
- Commercial Support –