New Phase 2 Data Published in New England Journal of Medicine Show Bardoxolone Methyl Sustained Improvement in Measure of Kidney Function (eGFR) Over 52 Weeks in Patients With Moderate to Severe Chronic Kidney Disease and Type 2 Diabetes
By Abbott, PRNEThursday, June 23, 2011
IRVING, Texas and ABBOTT PARK, Illinois, June 24, 2011 -
− 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 −
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.
Exploratory outcomes:
- 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
(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
About Abbott
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
Media, Matt Middleman, +1-212-845-4272, matt.middleman at russopartnersllc.com, or David Schull, +1-212-845-4271, david.schull at russopartnersllc.com, or Investors, Alan Roemer, aroemer at troutgroup.com, +1-646-378-2945, all for Reata; or Media, Raquel Powers, +1-847-935-6563, raquel.powers at abbott.com, or Tracy Sorrentino, +1-847-937-8712, tracy.sorrentino at abbott.com, or Financial, Larry Peepo, +1-847-935-6722, larry.peepo at abbott.com, or Liz Shea, +1-847-935-2211, liz.shea at abbott.com, all of Abbott
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