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Abstract: SA-OR39

Pooled Analyses of the Phase 3 Roxadustat Studies: Congestive Heart Failure Hospitalization Rates in Dialysis and Non-Dialysis Patients with Anemia Treated with Roxadustat vs. Comparators

Session Information

Category: Hypertension and CVD

  • 1402 Hypertension and CVD: Clinical, Outcomes, and Trials

Authors

  • Provenzano, Robert, Wayne State University, Detroit, Michigan, United States
  • Szczech, Lynda, FibroGen Inc, San Francisco, California, United States
  • Zhong, Ming, FibroGen Inc, San Francisco, California, United States
  • Lai, Bryant, FibroGen Inc, San Francisco, California, United States
  • Leong, Robert, FibroGen Inc, San Francisco, California, United States
  • Little, Dustin J., AstraZeneca, Gaithersburg, Maryland, United States
  • Yu, Kin-Hung Peony, FibroGen Inc, San Francisco, California, United States
Background

Roxadustat is an orally bioavailable hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. Phase 3 roxadustat studies were performed to treat anemia of chronic kidney disease (CKD). Congestive heart failure (CHF), a common comorbidity in CKD, was also analyzed. CHF is associated with a poorer prognosis in CKD patients, with a prevalence that increases with CKD severity; approximately 20% in mild CKD (>65 years) to 40% in patients on hemodialysis.

Methods

Safety data were pooled from pivotal phase 3 studies comparing roxadustat to placebo in Stage 3-5 non-dialysis-dependent (NDD) CKD patients, and to epoetin alfa in the overall dialysis-dependent (DD) patients, and subgroup of incident-dialysis (ID-DD) patients. Patients with baseline (BL) moderate to severe CHF were not enrolled. CHF hospitalization events were a component of the MACE-plus endpoints that were adjudicated by a blinded independent committee, and analyzed by a Cox proportional hazards regression model; these analyses were not powered for individual component endpoints.

Results

In the pooled NDD studies, 4270 patients were analyzed (2386 roxadustat; 1884 placebo). BL CHF history was comparable between roxadustat (13.0%) and placebo (13.6%) arms. Using ITT long-term follow-up, the HR (95% CI) of hospitalization for CHF among the NDD pooled population was 0.89 (0.72, 1.12) for roxadustat vs placebo. In the pooled DD studies, 3880 patients were analyzed (1940 roxadustat; 1940 epoetin alfa). BL CHF history was comparable between roxadustat (25.7%) and epoetin alfa (25.3%) arms, and in the incident dialysis (ID-DD) subgroup (≤4 months of dialysis at BL, n=1526) of 26.4 vs 27.0%, respectively. Using on-treatment analysis comparing roxadustat with epoetin alfa in the DD studies, the HR (95% CI) of hospitalized CHF was 0.73 (0.58, 0.94; p=0.013). In the ID-DD subgroup, the HR (95%CI) was 0.77 (0.42, 1.40).

Conclusion

Roxadustat showed a 27% reduction in risk for CHF hospitalization compared to epoetin alfa in the DD population, and a trend based on the point estimates toward reduction of risk compared to placebo in NDD, and to epoetin alfa in ID-DD patients.

Funding

  • Commercial Support