Abstract: SA-PO827

Roxadustat Treatment of CKD Anemia Is Not Influenced by Inflammation

Session Information

Category: Dialysis

  • 605 Dialysis: Anemia and Iron Metabolism

Authors

  • Szczech, Lynda, FibroGen, Inc., San Francisco, California, United States
  • Besarab, Anatole, FibroGen, Inc., San Francisco, California, United States
  • Saikali, Khalil Georges, FibroGen, Inc., San Francisco, California, United States
  • Poole, Lona, Fibrogen, Inc, San Francisco, California, United States
  • Saha, Gopal, FibroGen Inc, San Francisco, California, United States
  • Neff, Thomas B., FibroGen, Inc., San Francisco, California, United States
Background

The efficacy of ESAs in the treatment of anemia is diminished in inflammation. The hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat is being developed for treatment of CKD anemia. This analysis of Phase 2 studies was undertaken to explore the efficacy of roxadustat in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients with and without inflammation.

Methods

Data from five completed Phase 2 studies in NDD- and DD-CKD patients in both anemia correction and conversion of patients already treated for anemia were analyzed in this post hoc analysis. Among studies, roxadustat doses, study duration, and comparator (placebo or epoetin alfa) varied. Baseline (BL) hemoglobin (Hb) and change from BL (CFB) were summarized in the efficacy-evaluable populations among patient subgroups with BL CRP ≤ and > ULN (4.9 mg/L).

Results

A total of 234 NDD-CKD and 262 DD-CKD subjects were treated in these studies. Mean CFB in Hb with roxadustat versus comparator was summarized by study and inflammatory state.
Roxadustat-driven erythropoiesis, at similar doses, is clinically similar in inflamed versus non-inflamed NDD-CKD and DD-CKD subjects. In all studies, BL CRP correlated with hepcidin and roxadustat significantly reduced hepcidin in a dose-dependent fashion.

Conclusion

Roxadustat corrected and maintained Hb similarly in NDD-CKD and DD-CKD subjects both with and without inflammation, in contrast to ESA comparators, for which inflamed subjects had a less robust response. Phase 3 trials are currently underway to further establish the efficacy and safety of roxadustat.

Hemoglobin CFB among subgroups defined by inflammatory status
    Change from Baseline in HbChange from Baseline in Hb
StudyTreatment (N)Baseline CRP(mg/L)Baseline Hb(g/dL)noninflamed
subgroup
inflamed
subgroup
041Roxadustat (N=143)7.45 (±12.69)9.72 (± 0.67)1.70( ±0.12)1.54( ±0.18)
047Roxadustat (N=61)2.92 (± 9.33)8.81 (± 0.92)2.04( ±0.18)2.45( ±0.67)
 Placebo (N=30)1.48 (± 2.19)8.90 (± 0.82)0.37( ±0.18)-0.30( ±0.95)
040Roxadustat (N=94)8.85 (±12.13)11.21 (± 0.67)-0.29( ±0.23)0.39( ±0.23)
 Epoetin (N=31)7.37 (± 9.68)11.29 (± 0.84)-0.42( ±0.27)-0.60( ±0.34)
048Roxadustat (N=60)4.16 (± 7.00)10.76 (± 0.73)0.89( ±0.18)0.91( ±0.33)
 Epoetin (N=22)3.00 (± 4.70)10.59 (± 0.96)0.16( ±0.23)0.17( ±0.58)
053Roxadustat (N=55)6.74 (± 9.71)8.34 (± 1.03)2.74( ±0.24)2.09( ±0.33)

Noninflamed subgroup = Baseline CRP <= ULN. Inflamed subgroup = Baseline CRP > ULN. Mean±SD for baseline CRP and Hb. LSmean±SE for Hb CFB.

Funding

  • Commercial Support