Bardoxolone Methyl

Bardoxolone methyl, previously known as RTA 402, is the lead molecule in Reata's portfolio of Antioxidant Inflammation Modulators (AIMs). The AIMs are potent inducers of the transcription factor Nrf2, an important biological target that controls the production of many of the body's antioxidant and detoxification enzymes. Because oxidative stress and inflammation occur throughout the course of chronic kidney disease (CKD) and are known to contribute to loss of kidney function, agents that activate the Nrf2 pathway in patients with CKD may provide a novel method for preserving or improving kidney function. Bardoxolone methyl is currently being investigated as a potential oral once-a-day treatment for CKD.
Clinical observations in Phase 2 studies with bardoxolone methyl have included the following:

Significant and sustained improvements in eGFR.
Increased creatinine clearance, with no decrease in 24-hour creatinine excretion.
Parallel improvements in other measures of kidney function, including blood urea nitrogen and uric acid, which correlate with the improvement in eGFR.
Persisting increase in eGFR from baseline following withdrawal of therapy (when the drug has largely been cleared out of the body).

The five most frequently reported adverse events in the CKD studies (regardless of relationship to study drug) were muscle spasms, hypoglycemia, peripheral edema, nausea and hypomagnesaemia. A specific pattern of reversible transaminase elevations was also observed. In the placebo-controlled trial, hypoglycemia was reported in approximately equal proportions of patients in the bardoxolone methyl and placebo groups.

The ongoing multinational Phase 3 BEACON trial is currently enrolling patients to assess bardoxolone methyl's impact, compared to standard of care, on time to important clinical outcomes. The primary efficacy endpoint will be a composite of time-to-first event including progression to end stage renal disease (ESRD), defined by the need for dialysis or renal transplant and cardiovascular death.

Chronic Kidney Disease

CKD is a progressive loss of kidney function over a period of months or years that can be caused by a number of conditions, including diabetes and high blood pressure. CKD is a highly prevalent condition worldwide with numbers expected to rise over the next decade. In the United States there are more than 26 million patients with CKD, and more than 450,000 patients with end-stage renal disease (ESRD). For more information about the disease: