− Reata Pharmaceuticals, Inc. and Abbott plan further study: Newly begun Phase 3 study of bardoxolone methyl will enroll 1,600 patients in more than 300 clinical trial sites worldwide −
IRVING, Texas and ABBOTT PARK, Ill., June 24, 2011 /PRNewswire/ -- New Phase 2 clinical trial data published online today in The New England Journal of Medicine show that patients with moderate to severe chronic kidney disease and type 2 diabetes receiving bardoxolone methyl for 52 weeks experienced a sustained improvement in kidney function throughout the treatment period, as measured by estimated glomerular filtration rate (eGFR). The data were also presented today 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 (p<0.001).
"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 (p=0.002, 25 mg; p<0.001, 75 mg and 150 mg). This is consistent with what was observed at week 24 (the primary endpoint), when all treatment groups showed statistically significant improvement in eGFR with increases of 8.2, 11.4, and 10.4 mL/min/1.73m2 at 25, 75 and 150 mg, respectively.
- The most common adverse event associated with the bardoxolone methyl-treated group was muscle spasm (with incidence rates of 42%, 61% and 59% in the 25, 75 and 150 mg dose groups vs. 18% in the placebo group). Other adverse events more common to bardoxolone methyl-treated patients were transient elevations in liver enzymes, nausea, decreased appetite and hypomagnesemia.
- Nineteen percent of patients treated with placebo experienced a decline in eGFR (loss in kidney function) of more than 25% over 52 weeks, compared to 9% of bardoxolone methyl-treated patients (p=0.058).
- A statistically significant reduction in uric acid was also observed (p=0.026, 25 mg; p<0.001, 75 mg and 150 mg). Improvement was also seen in another important measure of kidney function, reduction in blood urea nitrogen (BUN), though this reduction did not reach statistical significance.
- Four weeks after study drug withdrawal, eGFR remained above baseline in each bardoxolone methyl-treated group, although this did not meet statistical significance, while patients on placebo experienced a modest decline.
"Chronic kidney disease and dialysis place enormous financial and social burdens on our society," said Paul Audhya, M.D., 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 Phase 2 data we have seen showing sustained improvements in eGFR are very encouraging," said Eugene Sun, M.D., Vice President, Global Pharmaceutical Research and Development, Abbott. "These results set the stage for our Phase 3 program for bardoxolone methyl, which will evaluate whether it is possible to delay or prevent progression to dialysis."
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. More information on the trial is available at www.clinicaltrials.gov (clinical trial identifier: NCT01351675).
About Chronic Kidney Disease
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 U.S. there are more than 26 million patients with CKD, and more than 450,000 patients with end-stage renal disease (ESRD).
About Bardoxolone Methyl
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 Phase 2 studies, including BEAM, bardoxolone methyl was shown to improve an important measure of kidney function (eGFR) in patients with moderate to severe CKD and type 2 diabetes. A Phase 3 study, currently underway, will evaluate the impact of bardoxolone methyl on important clinical outcomes.
In January 2010, Reata 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 formed a strategic partnership with Abbott for the development and commercialization of bardoxolone in other ex-U.S. markets. Reata retains exclusive rights to bardoxolone methyl in the U.S.
About Reata Pharmaceuticals
Reata Pharmaceuticals is the leader in discovering and developing novel, oral anti-inflammatory drugs that activate Nrf2, the primary regulator of cellular antioxidant and detoxification enzymes. Activation of this important biological target may protect against a broad range of diseases associated with inflammation and oxidative stress. Reata is developing bardoxolone methyl, its lead product candidate, as the first therapy specifically intended to improve or preserve kidney function.
For more information please visit the company's Web site at www.reatapharma.com.
Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacturing and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs nearly 90,000 people and markets its products in more than 130 countries.
Abbott's news releases and other information are available on the company's Web site at www.abbott.com.