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Abstract: PO1301

Integrated Analysis of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Warady, Bradley A., Children's Mercy Hospitals and Clinics, Kansas City, Missouri, 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 Grossman School of Medicine, New York, New York, United States
  • Block, Geoffrey A., US Renal Care, Plano, Texas, United States
  • Chapman, Arlene B., University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Chin, Melanie, Reata Pharmaceuticals Inc, Irving, 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, Irving, Texas, United States
  • Mariani, Laura H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Meyer, Colin John, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • O'Grady, Megan, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Stenvinkel, Peter, Karolinska Institutet, Stockholm, Stockholm, Sweden
  • Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States
Background

Alport syndrome is a rare and serious inherited form of CKD. An integrated analysis of efficacy and safety was conducted from the CARDINAL Phase 2/3 (NCT03019185) and EAGLE (NCT03749447) trials of bardoxolone methyl (Bard) in patients with Alport syndrome.

Methods

The CARDINAL Phase 2 trial was open-label and enrolled 30 patients ages 12 to 60 years with Alport syndrome, baseline eGFR values 30 to 90 mL/min/1.73 m2 and UACR ≤ 3500 mg/g. CARDINAL Phase 3 was an international, multi-center, double-blind, placebo-controlled trial with similar eligibility criteria and randomized 157 patients. EAGLE is an ongoing, open-label, extended access trial that is enrolling patients who completed CARDINAL Phase 2/3 trials.

Results

A total of 218 patients were included in the analysis (placebo: n=80, Bard: n=138). A majority (61%) of patients were female and receiving renin-angiotensin-aldosterone system inhibitor (83%). Mean age was 40 years, and 31 (14%) patients were <18 years old. Mean baseline eGFR was 60.4 and 62.3 mL/min/1.73 m2 and the maximum duration of exposure was 3.2 and 1.9 years for Bard and placebo groups, respectively.
The Bard group had significant increases in eGFR from baseline at the last on-treatment assessment (mean±SE: 3.37±1.21 mL/min/1.73 m2; p=0.006). Significant decreases in eGFR were seen in the placebo group (mean ± SE: -8.30±1.58 mL/min/1.73 m2; p<0.0001), resulting in a significant difference between groups after treatment withdrawal (p=0.03 vs placebo).
Consistent with prior studies, common adverse events (AE) included muscle spasms, aminotransferase increases, and hyperkalemia. Discontinuations due to AEs were uncommon (9 % of Bard and 5% of placebo groups). Across all studies, no major cardiac events were observed and no changes in blood pressure were observed.

Conclusion

Consistent with individually reported prior trials, an integrated Alport syndrome analysis set showed that Bard preserved kidney function with significant on- and off-treatment eGFR benefits and was generally well tolerated by patients.

Funding

  • Commercial Support