Kidney Week

Abstract: SA-OR97

Safety and Efficacy of Bardoxolone Methyl in Patients with Autosomal Dominant Polycystic Kidney Disease

Session Information

• Late-Breaking Science Orals - 2
  October 26, 2024 | Location: Room 6C, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Anand, Shuchi, Stanford University, Stanford, California, United States

Shuchi Anand, MD, MS

• Chimalapati, Suneeta, Biogen Inc, Cambridge, Massachusetts, United States

Suneeta Chimalapati, PhD

• Montez-Rath, Maria E., Stanford University, Stanford, California, United States

Maria E. Montez-Rath, PhD

• Goldsberry, Angie, Reata, Boston, Massachusetts, United States

Angie Goldsberry, MS

• Chin, Melanie, Reata, Boston, Massachusetts, United States

Melanie Chin, PhD

• Meyer, Colin John, Reata, Boston, Massachusetts, United States

Colin John Meyer, MD

• Khan, Samina, Reata, Boston, Massachusetts, United States

Samina Khan, MD, MPH

• Esteban de la Rosa, Rafael José, Universidad de Granada, Granada, Spain

Rafael José Esteban de la Rosa, MD, PhD

• Chapman, Arlene B., University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States

Arlene B. Chapman, MD

• Warady, Bradley A., Children's Mercy Kansas City, Kansas City, Missouri, United States

Bradley A. Warady, MD

• Chertow, Glenn M., Stanford University, Stanford, California, United States

Glenn M. Chertow, MD, MPH, FASN

Background

Interstitial fibrosis is a universal finding in nephrectomy samples from patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Bardoxolone methyl (BARD) activates the nuclear-factor-related factor 2 pathway, hypothesized to attenuate inflammation and fibrosis.

Methods

A phase 3, randomized 1:1, placebo-controlled clinical trial (NCT03918447) was designed to test the efficacy of BARD among patients with ADPKD and reduced eGFR (30-90ml/min/1.73 m² for patients 12-55 years, 30-44ml/min/1.73 m² for patients 56-70 years) and evidence of rapid eGFR decline (≥ 2.0ml/min/year for 2 years). The primary endpoint was off-treatment change from baseline eGFR at week 108 and the secondary endpoint was change from baseline at end of treatment (week 100). The trial was stopped prematurely by the sponsor, prior to meeting target enrollment.

Results

A total of 667 patients were enrolled, and eGFR (mean [SD]) at baseline were similar between randomized groups (BARD 51.6 [15.5] vs placebo 51.2 [16.8] mL/min/1.73m², respectively). 79 and 70 patients randomized to the placebo and Bard group had week 108 eGFR. There was no difference in the off-treatment (week 108) change from baseline (0.97 [95% CI –1.25, 3.19] mL/min/1.73m²), although end of treatment (week 100) eGFR was higher among patients randomized to the BARD group (7.9 [95% CI 6.41, 9.47] mL/min/1.73m²; Fig 1)). A majority of patients (89% placebo, 94% BARD) had treatment-emergent adverse events (TEAEs). The most common AEs in the group randomized to BARD were muscle spasms, aminotransferase elevations, and nausea. No one experienced serious cardiac events; one death occurred in the study (avalanche accident).

Conclusion

Among the subset of patients with available data on the primary endpoint in the FALCON trial, there was no evidence for preservation of eGFR among patients randomized to BARD at the end of 100 weeks of treatment and an 8-week washout period.

Funding

• Commercial Support – Reata