Abstract: PO0268
Risk of Transfusion in Patients with Dialysis-Dependent CKD Increases with Hemoglobin Levels <10 g/dL vs. ≥10 g/dL: Pooled Results from Roxadustat Phase 3 Studies
Session Information
- Anemia and Iron Management
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 200 Anemia and Iron Metabolism
Authors
- Provenzano, Robert, Wayne State University, Detroit, Michigan, United States
- Pecoits-Filho, Roberto, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
- Rastogi, Anjay, University of California Los Angeles, Los Angeles, California, United States
- Leong, Robert, FibroGen Inc, San Francisco, California, United States
- Saikali, Khalil Georges, FibroGen Inc, San Francisco, California, United States
- Pola, Maksym, AstraZeneca, Warsaw, Poland
- Little, Dustin J., FibroGen Inc, San Francisco, California, United States
- Yu, Kin-Hung Peony, FibroGen Inc, San Francisco, California, United States
Background
Roxadustat is a novel, orally bioavailable, heterocyclic small molecule that reversibly inhibits hypoxia-inducible factor (HIF) prolyl hydroxylase enzymes and activates HIF and transcription of HIF-responsive genes, including erythropoietin. In patients with ESRD, the risk for blood/RBC transfusion is higher in patients with hemoglobin (Hb) levels <10 g/dL vs. those with Hb ≥10 g/dL. We evaluated the efficacy of roxadustat vs. epoetin alfa on blood/RBC transfusion by Hb level in US-based patients with dialysis-dependent (DD) CKD.
Methods
Data from three pivotal phase 3, randomized, active-controlled studies of roxadustat for the treatment of anemia in DD patients were assessed. Patients were randomized to receive roxadustat or epoetin alfa with periodic dose evaluation/titration. Transfusion was allowed at any time if it was deemed a medical necessity by the Investigator. The incidence rate of transfusion was calculated based on Hb level categorized as: <8.0, 8 to <10, and ≥10 g/dL. Data were evaluated for the on-treatment period + 28 days after the last dose of study drug.
Results
In the overall pooled population of patients with DD-CKD, roxadustat vs. epoetin alfa reduced the risk for transfusion by 18% (HR, 0.82 [95% CI: 0.68, 1.00]; p=0.0461). When patient-exposure data were stratified by achieved Hb level, the risk for transfusion increased as Hb levels decreased (Table). The incidence rate of transfusion increased approximately 5-fold in patients with Hb <10 g/dL vs. those with Hb ≥10 g/dL.
Conclusion
In US-based patients with DD-CKD and anemia treated with roxadustat, the risk for transfusion was approximately 5 times higher in patients with Hb <10 g/dL vs. those with Hb ≥10 g/dL, regardless of treatment arm.
Table: Incidence rate of transfusion (events/100 PEY) based on Hb level and treatment group
| Roxadustat (n=874) | Epoetin alfa (n=879) | |||||||
| Hb (g/dL) | Events | PEY | Transfusion Rate* | % of PEY | Events | PEY | Transfusion Rate* | % of PEY |
| ≥10.0 | 72 | 1166.9 | 6.2 | 79.0 | 134 | 1208.8 | 11.1 | 69.3 |
| 8.0 to <10.0 | 93 | 288.1 | 32.3 | 19.5 | 160 | 507.8 | 31.5 | 29.1 |
| <8.0 | 51 | 22.4 | 227.7 | 1.5 | 57 | 28.2 | 202.1 | 1.6 |
| Total | 216 | 1477.4 | 14.6 | 100.0 | 351 | 1744.9 | 20.1 | 100.0 |
*Number of events per 100 PEY; Hb, hemoglobin; PEY, patient-exposure years
Funding
- Commercial Support – Fibrogen, Inc.; AstraZeneca plc; Astellas Pharma Inc.