Bardoxolone methyl shows promise in diabetic kidney disease
MedWire News: Bardoxolone methyl, a novel oral anti-oxidant inflammation modulator, significantly improves kidney function in patients with Type 2 diabetes and advanced chronic kidney disease (CKD) for up to 1 year, suggest findings from the BEAM study.
Bardoxolone methyl is a derivative of oleanolic acid and activates the Keap1-Nrf2 pathway, which is involved in preserving kidney structure and function.
Previous research has shown that 8 weeks of daily treatment with bardoxolone methyl significantly increases the glomerular filtration rate (GFR) in patients with Type 2 diabetes and chronic kidney disease; however, the long-term effects of treatment are unknown.
Pablo Pergola (University of Texas Southwestern, Dallas, USA) and co-workers undertook the BEAM (Bardoxolone Methyl Treatment: Renal Function in Chronic Kidney Disease/Type 2 diabetes) study, a double-blind, placebo-controlled randomized trial. Bardoxolone methyl was administered at doses of 25, 75, or 150 mg/day in the trial, which included 227 adults with Type 2 diabetes and advanced chronic kidney disease.
After 24 weeks of treatment, all doses of bardoxolone methyl had significantly improved the GFR compared with placebo, by 8.2 ml per 1.73m2 in patients who received 25 mg/day rising to 11.4 ml and 10.4 ml per 1.73m2 in patients who received 75 mg/day and 150 mg/day, respectively.
These improvements were maintained for up to 1 year, with the best response seen in patients who had received a bardoxolone methyl dose of 75 mg/day, in whom the GFR was 10.5 ml per 1.73m2 better at 52 weeks than in patients who received placebo.
Bardoxolone methyl treatment was generally well tolerated. Muscle spasms were the most common adverse event, with an incidence of up to 61%, but these were generally mild in nature. Treatment was also associated with manageable hypomagnesemia, raised alanine aminotransferase levels, and gastrointestinal disturbance.
"Patients with advanced chronic kidney disease and Type 2 diabetes who received treatment with bardoxolone methyl had sustained increases in the estimated GFR, a finding that is consistent with an improvement in kidney function," conclude the BEAM investigators.
"Thus, bardoxolone methyl appears to be an attractive therapeutic candidate for further study in patients with chronic kidney disease," the researchers add.
The results are reported in NEJM.
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By Philip Ford