Kidney Week

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

• Hypertension and Vascular Disease: From the Lab to Trials
  October 24, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Hypertension and CVD

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

Authors

• Provenzano, Robert, Wayne State University, Detroit, Michigan, United States

Robert Provenzano, MD, FASN



Robert Provenzano, MD, FACP, FASN, is a clinical professor of medicine at Wayne State University School of Medicine in Detroit, where he earned his medical degree. He completed his fellowship training at Henry Ford Hospital and served as the chief of the section of nephrology, hypertension and transplantation and director of nephrology research at St. John Hospital and Medical Center in Detroit.

• Szczech, Lynda, FibroGen Inc, San Francisco, California, United States

Lynda Szczech,

• Zhong, Ming, FibroGen Inc, San Francisco, California, United States

Ming Zhong,

• Lai, Bryant, FibroGen Inc, San Francisco, California, United States

Bryant Lai,

• Leong, Robert, FibroGen Inc, San Francisco, California, United States

Robert Leong,

• Little, Dustin J., AstraZeneca, Gaithersburg, Maryland, United States

Dustin J. Little,

• Yu, Kin-Hung Peony, FibroGen Inc, San Francisco, California, United States

Kin-Hung Peony Yu,

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 – Fibrogen, Inc.; AstraZeneca plc; Astellas Pharma Inc.