PRAGUE—Type 2 diabetics receiving the drug bardoxolone methyl experiences sustained improvement in their kidney function over the course of a 52-week treatment period, according to a phase 2 study published online June 24 in the New England Journal of Medicine.
The data were also presented in a Late-Breaking Clinical Trials session at the 2011 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress in Prague, Czech Republic.
The Phase 2 dose-finding clinical trial, known as the BEAM study, showed that in patients with moderate to severe chronic kidney disease—defined by an eGFR of 20 to 45 mL/min/1.73m2—and type 2 diabetes, eGFR at 52 weeks was significantly improved with bardoxolone methyl treatment by up to 10.5 mL/min/1.73m2 in patients receiving 75 mg.
Bardoxolone methyl is a novel, first-in-class antioxidant inflammation modulator (AIM). Bardoxolone activates the Nrf2 pathway, thereby inducing the transcription of genes that reduce oxidative stress and suppress important inflammatory mediators.
In January 2010, Reata Pharmaceuticals and Kyowa Hakko Kirin (KHK) announced a licensing agreement providing KHK with the exclusive rights to develop and commercialize bardoxolone in Japan and other selected Asian markets. In September 2010, Reata partnered with Abbott to develop and commercialize bardoxolone in other non-U.S. markets. Reata retains exclusive rights to bardoxolone methyl in the United States.
“The published data for bardoxolone methyl suggest that it may have potential to delay kidney disease progression in patients with compromised kidney function,” said Dr. David Warnock of the University of Alabama at Birmingham, who presented the findings at the ERA-EDTA session and is the senior author of the article. “Further study to learn more about the clinical benefits of this drug candidate is warranted.”
The multi-center, double-blind, placebo-controlled trial enrolled 227 patients who were randomly assigned to receive placebo, 25, 75 or 150 mg of bardoxolone methyl orally, once daily for 52 weeks.
Specifically, the 52-week data showed:
- At 52 weeks, patients receiving each of the three tested doses of bardoxolone methyl experienced a statistically significant improvement in eGFR, an important measure of kidney function. Increases were 5.8, 10.5 and 9.3 mL/min/1.73m2 for the 25, 75 and 150 mg groups, respectively, relative to placebo.
Exploratory outcomes:
- Nineteen percent of patients treated with placebo experienced a decline in eGFR (loss in kidney function) of more than 25 percent over 52 weeks, compared to 9 percent of bardoxolone methyl-treated patients.
- A statistically significant reduction in uric acid was also observed.
“Chronic kidney disease and dialysis place enormous financial and social burdens on our society,” said Paul Audhya, MD, Chief Medical Officer at Reata. “If these study results are confirmed in a Phase 3 clinical outcome study, bardoxolone methyl may prove to have a positive impact on the health of patients suffering from a debilitating disease, while potentially reducing the costs associated with its progression.”
The multinational Phase 3 BEACON trial will enroll approximately 1,600 patients with chronic kidney disease and type 2 diabetes at more than 300 sites worldwide. The primary objective of the study is to assess the impact of bardoxolone methyl on clinical outcomes, including time to dialysis or cardiac death. Results are expected in 2013.
