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Bardoxolone methyl, previously known as
RTA 402, is the lead molecule emerging from Reata’s platform of
Antioxidant Inflammation Modulators (AIMs).
The AIMs are the most potent known inducers of Nrf2, an important emerging biological target that controls the production of many of the body’s antioxidant and detoxification enzymes. There is a strong biological rationale for the use of agents targeting Nrf2 to treat renal and cardiovascular disease. Chronic oxidative stress-mediated inflammation is known to play an important role in the degeneration of kidney function. Based on data from three clinical studies demonstrating improvements in patients’ kidney function, bardoxolone has been advanced into late stage clinical development.
| Data from three clinical studies of bardoxolone methyl have demonstrated that the drug is: |
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Consistently producing a sustained improvement in kidney function assessed by multiple measures, including estimated glomerular filtration rate, cystatin C, and creatinine clearance |
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Improving glycemic control |
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Improving endothelial function |
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Well tolerated with an excellent safety profile |
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Modulating target biological pathway (Nrf2) |
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Potently inhibiting the production of pro-oxidant mediators (iNOS, COX2, peroxynitrite, and reactive oxygen and nitrogen species) |
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Regulating levels of important inflammatory cytokines (TNF, VEGF, IL-8, G-CSF) |
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Suitable for once daily oral dosing |
Data from clinical trials of bardoxolone methyl
were presented at major scientific meetings in the first half of 2009, including
two oral presentations at the American Diabetes Association's 69th
Annual Meeting in June and two posters at the National Kidney
Foundation's Spring Clinical Meeting in late March.
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Two Phase 1 clinical studies of bardoxolone demonstrated that the drug improved renal function in a high percentage of patients. To confirm these findings, Reata initiated a Phase 2a proof of concept study in patients with moderate to severe chronic kidney disease and type 2 diabetes mellitus. Based on highly promising results in this recently completed trial, Reata has advanced bardoxolone methyl into a larger Phase 2b study
in a similar patient population.
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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, wastes 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. Early detection and treatment can often keep chronic kidney disease from getting worse. As kidney disease progresses, it may eventually lead to kidney failure, requiring dialysis or a kidney transplant.
Chronic Kidney Disease Incidence and Mortality
The prevalence of chronic kidney disease has increased by 16 percent over the last 10 years as a result of the increasing incidence of diabetes mellitus, hypertension, obesity and an aging population. A recent report by the Centers for Disease Control determined that more than one in six adults (or 26 million Americans) have CKD. More than 400,000 patients are currently on dialysis or have received kidney transplants. About 67,000 people die each year because of kidney failure. CKD is more prevalent among individuals older than 60 years of age and among Hispanic, African American, Asian or Pacific Islander and Native American populations.
Risk Factors
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Diabetes - approximately
40 percent of diabetics, or 6 million people, are estimated to
have CKD, classifying them as having diabetic chronic kidney
disease, which results from longstanding diabetes mellitus and
is one of the primary causes of dialysis and kidney
transplantation. The average time from diagnosis of CKD to
end-stage renal disease is 16 years. |
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High blood pressure - independent of diabetic status, hypertension aids in the
progression of CKD and is the second leading cause of
end-stage renal disease. |
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Family history of kidney
failure – individuals who have a blood relative with kidney
failure are at increased risk for CKD. |
Screening Recommendations
The National Kidney Foundation (NKF) recommends that as a measure to control CKD, individuals who are at risk for the disease be tested for undetected kidney disease during routine health care encounters. Three simple, standardized tests are used to detect kidney disease: blood pressure measurement, urine test for protein and blood test for creatinine, which is used to calculate the level of kidney function. NKF recommends that patients with diabetes should be screened annually for CKD, with initial screening beginning five years after the diagnosis of type 1 diabetes and at the diagnosis of type 2 diabetes.
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