Abstract: PO0261
Risk of Transfusion in Patients with Non-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
- Coyne, Daniel W., Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, 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
- Szczech, Lynda, FibroGen Inc, San Francisco, California, United States
- Lee, Tyson T., FibroGen Inc, San Francisco, California, United States
- Pola, Maksym, AstraZeneca, Warsaw, Poland
- 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. placebo on blood/RBC transfusion by Hb level in US-based patients with non–dialysis-dependent (NDD) CKD.
Methods
Data from three pivotal phase 3, randomized, placebo-controlled studies of roxadustat for the treatment of anemia in NDD patients were assessed. Patients were randomized to receive roxadustat or placebo 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 NDD-CKD, roxadustat reduced the risk of transfusion by 74% (HR, 0.26 [95% CI: 0.21, 0.32]; p<0.0001) vs. placebo. When patient-exposure data were stratified by achieved Hb levels, the risk for transfusion increased as Hb levels decreased (Table). The incidence rate of transfusion increased approximately 4-fold in patients with Hb between 8.0 and <10.0 g/dL vs. those with Hb ≥10 g/dL regardless of treatment arm.
Conclusion
In US-based patients with NDD-CKD and anemia treated with roxadustat, the risk of transfusion was approximately 4 times higher in patients with Hb between 8.0 g/dL and <10 g/dL vs. those with Hb ≥10 g/dL.
Table: Incidence rate of transfusion (events/100 PEY) based on Hb level and treatment group
| Roxadustat (n=545) | Placebo (n=436) | |||||||
| Hb (g/dL) | Events | PEY | Transfusion Rate* | % of PEY | Events | PEY | Transfusion Rate* | % of PEY |
| ≥10.0 | 50 | 780.7 | 6.40 | 84.7 | 13 | 181.7 | 7.16 | 31.5 |
| 8.0 to 10.0 | 35 | 133.5 | 26.21 | 14.5 | 93 | 349.1 | 26.64 | 60.5 |
| <8.0 | 14 | 8.0 | 175.22 | 0.9 | 81 | 46.4 | 174.42 | 8.0 |
| Total | 99 | 922.3 | 10.73 | 100.0 | 187 | 577.3 | 32.39 | 100.0 |
*Number of events per 100 PEY; Hb, hemoglobin; PEY, patient-exposure years
Funding
- Commercial Support – Fibrogen, Inc.; AstraZeneca plc; Astellas Pharma Inc.