Phase II Results Demonstrate Significant Increase in Glomerular Filtration Rate in Diabetic Patients with Advanced Chronic Kidney Disease
IRVING, Texas, June 6 /PRNewswire/ -- Reata Pharmaceuticals, Inc. today announced that results of a Phase II clinical trial of bardoxolone, its lead antioxidant inflammation modulator (AIM), conducted in 60 diabetic patients with advanced chronic kidney disease (CKD) will be the subject of two oral presentations at the 69th annual meeting of the American Diabetes Association. The final data from the study demonstrated that patients treated with bardoxolone experienced a greater than 20 percent increase (p<0.0001) over baseline in their estimated glomerular filtration rate (GFR), a measure of the kidney’s filtration capacity and the primary endpoint of the study. CKD is a progressive and incurable disease, and currently approved treatments only modestly reduce the rate of decline in the kidney’s GFR over time. In the bardoxolone CKD study, approximately 90 percent of patients on drug experienced an increase in their GFR, and patients with more severe stage 4 CKD at baseline experienced an even greater (36 percent) increase in GFR (p<0.0001). Based on the results of this Phase II clinical trial, Reata has initiated a longer term, late stage trial of bardoxolone in patients with diabetes and advanced CKD.
Bardoxolone and other AIMs activate Nrf2 a transcription factor or “master gene” which controls the production of over 250 antioxidant and detoxification proteins. Activation of Nrf2 promotes the resolution of chronic inflammation by interrupting reactive oxygen driven pro-inflammatory signaling. The hyperglycemia experienced by diabetics causes excessive production of reactive oxygen in the kidney and vasculature, and the resulting chronic inflammation is believed to be a significant cause of diabetic complications such as CKD and cardiovascular disease.
Lead investigator and study presenter Dr. Sherwyn Schwartz commented, “This study of bardoxolone is very encouraging. These results suggest for the first time that diabetic patients with kidney disease may be able to regain some kidney function and perhaps stop the progression toward end stage renal disease and dialysis.” Dr. Schwartz is the Vice President of Scientific Affairs of dgd Research and Medical Director of the Diabetes & Glandular Disease Clinic in San Antonio, Texas.
Study Design, Patient Population, and Results
The bardoxolone CKD study was an open-label, randomized, dose-ranging study designed to test the efficacy of bardoxolone in diabetic patients with stage 3 or 4 CKD. Sixty patients were randomized to receive 25, 75 or 150 mg per day of bardoxolone in addition to standard therapy for 28 days. The primary endpoint for the study was a change from baseline in estimated GFR. The study also assessed the drug’s impact on measures of glycemic control and cardiovascular disease.
The trial enrolled patients with a long-term history of diabetes (average of 19 years) and significant diabetic complications including CKD. All patients had significant renal impairment at baseline, with a mean GFR of 36 ml/min/1.73 meters squared, representing a loss of almost two thirds of kidney function compared with a normal, healthy adult. Over one-third of subjects had severe or stage 4 CKD, with a GFR of less than 30 ml/min/1.73 meters squared. These patients would be expected to progress to end stage renal disease (and require dialysis or a kidney transplant) within one to three years with currently available treatments.
Patients treated with bardoxolone experienced a 20.5 percent mean increase in estimated GFR over baseline (p<0.0001). Patients with stage 4 CKD at baseline experienced a 36 percent mean increase in estimated GFR over baseline (p<0.0001). The renal function improvements were highly consistent with approximately 90 percent of patients experiencing an increase in estimated GFR from baseline during the study. Significant improvements were also seen in other markers of renal function (creatinine clearance, blood urea nitrogen, phosphorus, and uric acid), glycemic control (glycosylated hemoglobin A1C and fasting plasma glucose), and cardiovascular disease (circulating endothelial cells, angiotensin II, and adiponectin).
Bardoxolone Program Status
Based on the results of this Phase II clinical trial, as well as two previous trials demonstrating similar effects in other patient populations, Reata has initiated a larger, longer-term study of bardoxolone in diabetic patients with CKD. This Phase IIb study will enroll a total of 200 patients to be treated for one year. Results will be available during 2010.
Bardoxolone Presentation Details
Results for the primary and related renal function endpoints from the phase II clinical trial evaluating bardoxolone in diabetic patients with advanced CKD will be the subject of an oral presentation at 4:00 PM CDT on June 6, 2009.
Title: Bardoxolone Methyl Shown to Improve Renal Function in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus
Authors: Sherwyn Schwartz, M.D., Douglas Denham, D.O., Craig Hurwitz, M.D., Colin Meyer, M.D., Pablo Pergola, M.D., Ph.D.
Session: Novel Diabetes Therapies in Development in Humans
Time: 4:00 PM CDT
Location: Morial Convention Center, New Orleans, LA, Room Louisiane C
Abstract No. 112-OR
Results for the glycemic control endpoints from the phase II clinical trial evaluating bardoxolone in diabetic patients with advanced CKD will be the subject of an oral presentation at 5:15 PM CDT on June 8, 2009.
Title: Bardoxolone, a Novel Oral Anti-Inflammatory Agent Improves Glycemic Control in Type 2 Diabetics with Chronic Kidney Disease
Session: New Treatments in Development
Authors: Sherwyn Schwartz, M.D., Douglas Denham, D.O., Craig Hurwitz, M.D., Colin Meyer, M.D., Pablo Pergola, M.D., Ph.D.
Time: 5:15 PM CDT
Location: Morial Convention Center, New Orleans, LA, Hall E-2
Abstract No. 362-OR
About Chronic Kidney Disease
CKD is a progressive loss of kidney function over a period of months or years, which can be caused by a number of conditions, including diabetes and high blood pressure. As kidney disease gets worse, waste products can build to high levels in the blood and patients may develop complications like high blood pressure, anemia (low blood count), weak bones, poor nutritional health and nerve damage. CKD also increases the risk of having heart and blood vessel disease. As kidney disease progresses, it eventually leads to kidney failure, requiring dialysis or a kidney transplant.
About Reata
Reata Pharmaceuticals, Inc. is a biopharmaceutical company focused on translating innovative science into breakthrough medicines for intractable diseases. Reata is the leader in discovering and developing novel anti-inflammatory drugs targeting Nrf2, which controls the production of antioxidants and has been shown to protect against a broad range of diseases associated with inflammation and oxidative stress. Reata is developing a portfolio of AIMs for a variety of inflammation-related diseases. The company’s most advanced program is in late-stage clinical development for CKD, a progressive condition affecting more than 26 million Americans. For more information, visit www.reatapharma.com.
CONTACT: Rachael Schwartz, +1-215-885-3531, Cell: +1-267-253-2380,
rschwartz@rachaelschwartzcomm.com
Web site: http://www.reatapharma.com/
