Abstract: FR-OR54
Integrated Efficacy and Safety of Bardoxolone Methyl in CKD
Session Information
- Findings from Landmark Trials, Other Kidney Trials, and Observational Studies
November 05, 2021 | Location: Simulive, Virtual Only
Abstract Time: 04:30 PM - 06:00 PM
Category: CKD (Non-Dialysis)
- 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Mariani, Laura H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
- Agarwal, Rajiv, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Andreoli, Sharon P., Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, United States
- Bangalore, Sripal, New York University, New York, New York, United States
- Block, Geoffrey A., US Renal Care, Inc, Plano, Texas, United States
- Chapman, Arlene B., University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States
- Chin, Melanie, Reata Pharmaceuticals Inc, Plano, Texas, United States
- Devarajan, Prasad, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Gibson, Keisha L., University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
- Goldsberry, Angie, Reata Pharmaceuticals Inc, Plano, Texas, United States
- Meyer, Colin John, Reata Pharmaceuticals Inc, Plano, Texas, United States
- O'Grady, Megan, Reata Pharmaceuticals Inc, Plano, Texas, United States
- Stenvinkel, Peter, Karolinska Institutet, Stockholm, Stockholm, Sweden
- Warady, Bradley A., Children's Mercy Hospitals and Clinics, Kansas City, Missouri, United States
- Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
Background
Bardoxolone methyl (Bard), an Nrf2 activator, has been studied in multiple CKD trials. To further characterize the safety and efficacy of Bard, we performed integrated analyses across all studies conducted with Bard in CKD.
Methods
Data from the following placebo-controlled trials, CARDINAL Phase 3 (NCT03019185) in 157 patients with Alport syndrome, TSUBAKI (NCT02316821) in 120 patients with T2DM and CKD, and BEACON (NCT01351675) in 2185 patients with T2DM and CKD, were pooled in a CKD Placebo-Controlled Set. An Overall Integrated Analysis Set included additional data from open-label Phase 2 studies.
Results
The CKD Placebo-Controlled Set included 2462 patients (1232 placebo, 1230 Bard). The median and maximum duration of exposure for the Bard group was 0.5 years and 1.9 years, respectively. The Overall Integrated Analysis Set included 3448 patients (1340 placebo, 2108 Bard) with a maximum Bard exposure of 4.8 years.
In the CKD Placebo-Controlled Set, Bard significantly increased eGFR from baseline by 6.4±0.2 mL/min/1.73m2 (p<0.0001) at the last on-treatment assessment while the placebo group had a significant decrease in eGFR (mean±SE:-1.1±0.2 mL/min/1.73m2;p<0.0001). The eGFR increases with Bard were sustained four weeks after treatment withdrawal (1.5±0.2 mL/min/1.73m2; p<0.0001 vs baseline and vs placebo). Fewer events in a composite of ESKD, ≥30% decline in eGFR, and eGFR <15 mL/min/1.73m2 were seen in the Bard group (111 [9%]) compared to placebo (274 [22%]). The Overall Integrated Analysis Set showed similar results.
Common adverse events (AEs) in both integrated sets included muscle spasms, decreased appetite, hypomagnesaemia and decreased weight. No serious AEs of cardiac failure were reported with Bard in CKD trials conducted after BEACON.
Conclusion
Across all studies in CKD, Bard preserved kidney function with on- and off-treatment eGFR benefits and was generally well tolerated. Studies in persons with CKD conducted after BEACON mitigated the risk for heart failure previously observed in patients with type 2 diabetes and Stage 4 CKD.
Funding
- Commercial Support –