Kidney Week

Abstract: FR-PO241

Primary Efficacy Analyses from a Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients with Autosomal Dominant Polycystic Kidney Disease

Session Information

• CKD: Clinical, Outcomes, Trials - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Pergola, Pablo E., Renal Associates, PA, San Antonio, Texas, United States

Pablo E. Pergola,

• Appel, Gerald B., Columbia University College of Physicians and Surgeons, Scarsdale, New York, United States

Gerald B. Appel,

• Awad, Ahmed M., Clinical Research Consultants, LLC, Kansas City, Missouri, United States

Ahmed M. Awad,

• Betts, Judith A., Austin Kidney Associates, Austin, Texas, United States

Judith A. Betts,

• Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States

Geoffrey A. Block,

• Chin, Melanie, Reata Pharmaceuticals, Irving, Texas, United States

Melanie Chin,

• Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States

Lesley Inker,

• Meyer, Colin John, Reata Pharmaceuticals, Irving, Texas, United States

Colin John Meyer,

• Rastogi, Anjay, University of California at Los Angeles Medical Center, Los Angeles, California, United States

Anjay Rastogi,

• Rizk, Dana, University of Alabama, Birmingham, Alabama, United States

Dana Rizk,

• Schroeder, Kevin, Ohio Kidney Consultants, Columbus, Ohio, United States

Kevin Schroeder,

• Silva, Arnold L., Boise Kidney & Hypertension Institute, Meridian, Idaho, United States

Arnold L. Silva,

Background

Bardoxolone methyl (BARD) has been shown to significantly increase eGFR in patients with CKD and type 2 diabetes or Alport syndrome suggesting that the anti-inflammatory and anti-fibrotic effects of BARD may target common pathways contributing to GFR loss in multiple forms of CKD. Inflammation seems to correlate with disease initiation and progression in polycystic kidney disease (PKD). As a result, a Phase 2 trial (PHOENIX, NCT03366337) was initiated to determine if BARD will improve kidney function in patients with autosomal dominant PKD (ADPKD).

Methods

The open-label, multicenter study enrolled 31 patients with ADPKD with genetic confirmation of PKD1 mutation. Eligible patients (18 to 65 years of age) had eGFR values between 30 to 90 mL/min/1.73 m² and urine albumin to creatinine ratio (UACR) ≤ 2500 mg/g. Patients received BARD at an initial dose of 5 mg, dose-escalated up to 20 mg (for patients with baseline UACR ≤ 300 mg/g) or up to 30 mg (for patients with baseline UACR > 300 mg/g) and were treated for 12 weeks. The primary efficacy endpoint was the change from baseline eGFR after 12 weeks of treatment. Interim results are described herein.

Results

At data cutoff on May 15^th, 2018, all 31 of the patients had completed Week 4 and 8/31 (26%) had completed the study. From a mean (±SE) baseline eGFR of 47.7 ± 2.4 mL/min/1.73 m², BARD treatment resulted in a significant increase in eGFR of 6.6 ± 0.9 mL/min/1.73 m² (n=31; p<0.0001) at Week 4 and 12.0 ± 1.4 mL/min/1.73 m² (n=8; p<0.0001) at Week 12. The improvements were consistent, all 8 (100%) of the patients had increases in eGFR at Week 12. UACR was not significantly different from baseline. No patients have discontinued from the study and no serious AEs considered related to BARD have been reported in this ongoing trial.

Conclusion

BARD was generally well tolerated and significantly increased eGFR in patients with ADPKD. In patients with other forms of CKD, short term eGFR increases with BARD are predictive of durable eGFR improvements and additional studies are needed to study the longer-term effects of BARD on eGFR in ADPKD.

Funding

• Commercial Support –