ABOUT BARDOXOLONE METHYL
Bardoxolone methyl is an investigational drug in a class of drugs called Nrf2 activators. It is a capsule taken by mouth, once daily. To date, bardoxolone methyl has been studied in sixteen completed studies (seven in patients with CKD who also had type 2 diabetes, four in non-CKD indications, and five in healthy subjects) and four ongoing studies (three in patients with pulmonary hypertension and one in patients with Alport syndrome).
Research completed to date suggests that bardoxolone methyl:
- Decreases inflammation in the kidney, protects the kidney from injury, and prevents fibrosis (changes in the structures) within the kidney, based on data from animal models
- Significantly increases glomerular filtration rate (GFR) in patients with diabetic kidney disease
- Produces eGFR increases that are sustained for at least one year, with a portion of the increase retained even 4 weeks after stopping treatment, in patients with diabetic kidney disease
A previous large study that enrolled over 2,000 diabetic patients with severe stage 4 chronic kidney disease was stopped early because bardoxolone methyl increased the risk for fluid retention in a subset of patients who had previously been hospitalized for heart failure and who had fluid retention prior to the start of the study. The increased risk for fluid retention was only observed in the first month after starting treatment. The identified risk factors are now used to exclude patients who are more likely to retain fluid from participating in studies with bardoxolone methyl. To date, bardoxolone methyl has not been shown to increase the risk for fluid retention in subsequent studies, including those in diabetic chronic kidney disease, chronic kidney disease due to Alport syndrome, and pulmonary arterial hypertension patients.
Other less severe side effects have been observed in some patients in other trials with bardoxolone methyl, including muscle spasms, pain (back, abdominal, extremities), low magnesium, and nausea, swelling in the limbs, and decreased appetite, among others. Additional information regarding potential side effects and risks of participation will be provided during the informed consent process.
The PHOENIX trial will exclude patients with highly advanced kidney disease and the above risk factors. Additionally, patients with significant left-sided heart disease or cardiac diseases are excluded from participating. Patients will be monitored closely during the first two months of the trial to ensure that they do not develop fluid retention.
How Might Bardoxolone Methyl Treat Your Condition?
Your estimated glomerular filtration rate (eGFR) is a measure of how well your kidneys are working. Inflammation in kidney disease causes changes within your kidney that limit the kidney’s ability to filter out wastes and excess fluid in your body. Increased inflammation from kidney disease reduces kidney function and causes decreases in eGFR.
Decreasing eGFR ultimately results in the need for dialysis or kidney transplant. In previous studies in patients with diabetes and chronic kidney disease, bardoxolone methyl produced an increase in eGFR that was sustained for 1 year in some patients. It is not known whether an increase in eGFR, if achieved, will provide long-term benefit in patients with CKD associated with type 1 diabetes (T1D), IgAN, FSGS, or ADPKD.
Consequently, the PHOENIX study is designed to test the safety and effects of bardoxolone methyl on eGFR in these different kidney diseases during and after 12 weeks of treatment with bardoxolone methyl.