Abstract: SA-PO918
A Cardiovascular Risk Mitigation Strategy on the Safety of Bardoxolone Methyl Post-BEACON
Session Information
- CKD: Clinical, Outcomes, Trials - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
- 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
- Kanda, Hironori, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan
- Meyer, Colin John, Reata Pharmaceuticals, Inc., Irving, Texas, United States
- Pergola, Pablo E., Renal Associates, P.A., San Antonio, Texas, United States
- Sprague, Stuart M., NorthShore University HealthSystem University of Chicago, Chicago, Illinois, United States
- Stenvinkel, Peter, Karolinska University Hospital Huddinge, Stockholm, Sweden
- Wanner, Christoph, University Hospital, Wuerzburg, Germany
- McCullough, Peter A., Baylor University Medical Center, Dallas, Texas, United States
Background
Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON) was a multinational, randomized, double-blind, placebo-controlled Phase 3 trial that enrolled patients with type 2 diabetes (T2D) and stage 4 CKD. The BEACON trial was terminated due to a significant increase in the risk of heart failure occurring within the first four weeks of treatment with bardoxolone methyl (Bard). Post-hoc analyses identified a history of heart failure and elevated baseline serum concentrations of B-type natriuretic peptide (BNP) as risk factors for these events. Four subsequent clinical trials in other disease states have excluded patients with these clinical characteristics. Additionally, BNP and NT-proBNP were measured as safety parameters over the course of these trials. Safety data from these trials will be presented.
Methods
Data from four studies were included: a 48-week, open-label Phase 2 study in patients with Alport syndrome (CARDINAL; NCT03019185); a 12-week, open-label Phase 2 study in patients with autosomal dominant polycystic kidney disease, IgA nephropathy, focal segmental glomerulosclerosis, or type 1 diabetes CKD (PHOENIX; NCT03366337); a 16-week, randomized, placebo-controlled, double-blind Phase 2 study patients with T2D and CKD in Japan (TSUBAKI; NCT02316821); and a 16-week, randomized, placebo-controlled, double-blind, global Phase 2 study of pulmonary hypertension (PH) (LARIAT; NCT02036970).
Results
A total of 423 patients were enrolled in four studies that were initiated after the termination of BEACON. There were no fluid overload-related serious adverse events in any patients treated with Bard in any of these studies. Treatment with Bard was not associated with increases in mean blood pressure in any of these studies. Mean decreases in body weight were apparent by Week 12 of treatment with Bard and were more pronounced in patients with higher baseline BMI.
Conclusion
In four clinical studies that enrolled over 400 patients without elevated BNP or a history of heart failure, Bard did not result in an increased differential risk of heart failure, other signs of overt fluid overload or subclinical measures of fluid retention (increases in blood pressure or weight).
Funding
- Commercial Support –