Reata Presents Promising Data on Bardoxolone at American Diabetes Association
Annual Scientific Meeting
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.
SOURCE Reata Pharmaceuticals, Inc.
Rachael Schwartz, +1-215-885-3531, Cell: +1-267-253-2380,
rschwartz@rachaelschwartzcomm.com
