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Kidney Week

Abstract: TH-PO444

Effect of Bardoxolone Methyl on Kidney Events in Patients with CKD Stage 4 and Type 2 Diabetes at High Risk of Adverse Kidney Outcomes

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Wanner, Christoph, University Hospital, Wuerzburg, Germany
  • Appel, Gerald B., Columbia University College of Physicians and Surgeons, Scarsdale, New York, United States
  • Block, Geoffrey A., Reata Pharmaceuticals, Inc., Irving, Texas, United States
  • Chin, Melanie, Reata Pharmaceuticals, Inc., Irving, Texas, United States
  • Coyne, Daniel W., Washington University School of Medicine, St. Louis, Missouri, United States
  • Goldsberry, Angie, Reata Pharmaceuticals, Inc., Irving, Texas, United States
  • Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States
  • Meyer, Colin John, Reata Pharmaceuticals, Inc., Irving, Texas, United States
  • Sprague, Stuart M., NorthShore University HealthSystem University of Chicago, Chicago, Illinois, United States
  • Stenvinkel, Peter, Karolinska University Hospital Huddinge, Stockholm, Sweden
  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
Background

Increases in kidney function, including increases in inulin clearance and estimated glomerular filtration rate (eGFR), have been observed with bardoxolone methyl (Bard) in 11 studies enrolling approximately 3,000 patients with chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial, which enrolled patients with type 2 diabetes and stage 4 CKD. We performed a post-hoc analysis of BEACON to characterize changes in kidney function induced by Bard in subgroups of patients at particularly high risk of adverse kidney outcomes, including those with baseline eGFR below 22 mL/min/1.73 m2 or with a urine albumin to creatinine ratio (UACR) > 300 mg/g.

Methods

Patients in BEACON (n=2185; NCT01351675) were randomized 1:1 to receive once-daily bardoxolone methyl (20 mg) or placebo. For the subsets of patients with baseline eGFR < 22 mL/min/1.73 m2 (n=503 for Bard, n=514 for placebo) or baseline UACR > 300 mg/g (n=540 for Bard, n=578 for placebo), we compared the effects of Bard and placebo on a post-hoc composite kidney endpoint consisting of a sustained ≥30% decline from baseline in eGFR, sustained eGFR <15 mL/min/1.73 m2, and end-stage kidney disease events.

Results

Patients with baseline eGFR < 22 mL/min/1.73 m2 randomized to Bard were significantly less likely to experience the composite kidney endpoint than patients randomized to placebo; 45/503 (9%) Bard patients experienced an event compared to 111/514 (22%) placebo patients (hazard ratio 0.39; 95% CI, 0.28-0.55; p<0.001). For patients with baseline UACR > 300 mg/g, 58/540 (11%) Bard patients experienced an event compared to 105/578 (18%) placebo patients (hazard ratio 0.58; 95% CI, 0.42-0.80; p<0.001).

Conclusion

In the subsets of patients enrolled in BEACON who were at greatest risk for progression to kidney failure, the increases in eGFR with Bard were associated with a significant reduction in the likelihood of an end-stage kidney disease composite endpoint.

Funding

  • Commercial Support