ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-OR131

Pooled Efficacy and Cardiovascular (CV) Analyses of Roxadustat in the Treatment of Anemia in CKD Patients on and Not on Dialysis

Session Information

  • High-Impact Clinical Trials
    November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
    Abstract Time: 02:00 PM - 02:15 PM

Category: Anemia and Iron Metabolism

Authors

  • Provenzano, Robert, Wayne State, Detroit, Michigan, United States
  • Fishbane, Steven, Northwell Health, Commack, New York, United States
  • Wei, Lee-Jen, Harvard University, Boston, Massachusetts, United States
  • Szczech, Lynda, FibroGen, Inc., San Francisco, California, United States
  • Leong, Robert, FibroGen, Inc., San Francisco, California, United States
  • Saikali, Khalil Georges, FibroGen, Inc., San Francisco, California, United States
  • Zhong, Ming, FibroGen, Inc., San Francisco, California, United States
  • Lee, Tyson T., FibroGen, Inc., San Francisco, California, United States
  • Houser, Mark T., AstraZeneca, Mölndal, Sweden
  • Frison, Lars, AstraZeneca, Mölndal, Sweden
  • Houghton, John, AstraZeneca, Mölndal, Sweden
  • Neff, Thomas B., FibroGen, Inc., San Francisco, California, United States
  • Yu, Kin-Hung Peony, FibroGen, Inc., San Francisco, California, United States

Group or Team Name

  • Dr. Provenzano and Dr. Fishbane contributed equally.
Background

Roxadustat is an oral hypoxia–inducible factor prolyl hydroxylase inhibitor that regulates erythropoiesis & iron metabolism. Integrated Phase 3 analyses examine efficacy & safety of roxadustat in CKD patients (pts).

Methods

Phase 3 studies comparing roxadustat to placebo (pbo), in pts with Stage 3-5 non-dialysis-dependent CKD (NDD) & epoetin alfa in dialysis-dependent (DD) patients were pooled. Death, MI, & stroke (MACE), & heart failure or unstable angina requiring hospitalization (MACE+) were adjudicated. Efficacy analyses assessed Hb & rescue therapy (transfusion, IV iron & ESA). CV endpoints included MACE & MACE+.

Results

In NDD, 4270 pts were randomized (2386 roxadustat;1884 pbo). The primary endpoint (mean Hb CFB; Wks 28-52) was +1.85(.94)g/dL in the roxadustat group v. +.13(±1.01)g/dL in pbo (p<.0001) with lower risk of rescue therapy HR(95% CI)=.19 (.16,.23;81% reduction,p<.0001) in roxadustat. Using ITT long-term follow-up, the HR for time to MACE was 1.08(95%CI .94,1.24) for roxadustat vs. pbo, & 1.04(95% CI .91,1.18) for MACE+. In the subgroup with eGFR>10 (n=3431), MACE HR(95% CI)=.99(.84,1.16) & MACE+ HR=.98 (.85,1.14), for roxadustat v. pbo.

In DD, 3917 patients were randomized (1960 roxadustat;1957 epoetin alfa). The primary endpoint (mean Hb CFB Wk 28-52) was 1.21 in roxadustat v. .95 g/dL in EPO (difference .26 g/dL;95%CI .20,.33) in pooled analysis; roxadustat was noninferior & superior to EPO (p<.0001). The roxadustat group received fewer transfusions, 9.5 v.12.8%; HR(95%CI) =.82(.679,.997). Comparing roxadustat with EPO, HR for MACE = .95 (95% CI .81,1.12) & for MACE+ HR=.84 (.73,.97;p=.02) in DD pts. Of 1526 incident pts (dialysis <4 months), HRs for MACE & MACE+ =.70 (95% CI .51,.97)(p=.03) & .66 (95%CI .50,.89)(p=.005).

Conclusion

These integrated Phase 3 analyses provide evidence for roxadustat superiority in anemia correction with transfusion reduction & acceptable CV safety profile.

Funding

  • Commercial Support