AstraZeneca
(NYSE: AZN) and Bristol-Myers
Squibb Company (NYSE: BMY) today announced results from a Phase III
study evaluating dapagliflozin in adult patients with type 2 diabetes
who were inadequately controlled on combination treatment with metformin
plus sulfonylurea. Patients treated with dapagliflozin 10 mg as an
add-on therapy to metformin plus sulfonylurea demonstrated significant
improvements in glycosylated hemoglobin levels (HbA1c) and, among key
secondary endpoints, significant reductions in fasting plasma glucose
(FPG) and in body weight compared to placebo at 24 weeks. Significant
improvements were also observed in seated systolic blood pressure (SBP)
at eight weeks in patients treated with dapagliflozin compared to
placebo. The results were presented today at the 49th Annual
Meeting of the European Association for the Study of Diabetes (EASD) in
Barcelona, Spain.
In this study, overall rates of adverse events were similar between the
two treatment groups, and most were reported as mild or moderate in
intensity. More patients in the dapagliflozin group reported
hypoglycemia, genital infection and renal adverse events compared to the
placebo group. Rates of urinary tract infection were the same for both
groups.
“The improvements in glycemic control combined with the significant
reduction in body weight observed in this study add to the clinical
profile of dapagliflozin, specifically when used as part of a triple
oral therapy regimen with metformin and sulfonylurea,” said Stephan
Matthaei, M.D., primary study investigator and director of the Diabetes
and Metabolism Center, Quakenbrück Hospital, Quakenbrück, Germany.
Dapagliflozin is a selective and reversible inhibitor of sodium-glucose
cotransporter 2 (SGLT2), which works independently of insulin. It is
currently approved for the treatment of type 2 diabetes in the European
Union, Australia, Brazil, Mexico and New Zealand. A resubmission of the
New Drug Application (NDA) for dapagliflozin was accepted for review by
the U.S. Food and Drug Administration (FDA) in July 2013 with a new
Prescription Drug User Fee Act (PDUFA) goal date of January 11, 2014.
Study Results
At the end of 24 weeks, patients treated with dapagliflozin 10 mg added
to metformin plus sulfonylurea demonstrated significantly greater
improvements in glycemic control compared to those who received placebo,
with a mean change from baseline in HbA1c of -0.86% (95% Confidence
Interval [CI]: -1.00, -0.72) in the dapagliflozin group versus -0.17%
(95% CI: -0.31, -0.02) in the placebo group (p-value < 0.0001).
Additional results of the key secondary endpoints included the following:
-
More patients treated with dapagliflozin (31.8%) achieved an HbA1c <
7.0% compared to patients who received placebo (11.1%) at week 24
(p-value < 0.0001).
-
At week 24, patients treated with dapagliflozin showed significant
improvements in adjusted mean FPG (-34.23 mg/dL; 95% CI: -40.98,
-27.48) compared to patients who received placebo (-0.78 mg/dL; 95%
CI: -7.56, 6.01; p-value < 0.0001).
-
Patients treated with dapagliflozin experienced significant reductions
in mean body weight (-2.65 kg; 95% CI: -3.16, -2.14) at week 24
compared to patients who received placebo (-0.58 kg; 95% CI: -1.09,
-0.07; p-value < 0.0001).
-
At week eight, patients treated with dapagliflozin had significant
reductions in mean SBP (-4.04 mmHg) compared to patients who received
placebo (-0.27 mmHg; p-value = 0.025).
Overall, 48.6% of patients in the dapagliflozin group and 51.4% of
patients in the placebo group experienced ≥ 1 adverse events, most of
which were reported as mild or moderate in intensity. Adverse events of
special interest occurring during the 24 weeks included hypoglycemia
(12.8% for dapagliflozin vs. 3.7% for placebo; no major episodes
observed), urinary tract infection (6.4% for dapagliflozin vs. 6.4% for
placebo), genital infection (5.5% for dapagliflozin vs. 0% for placebo)
and renal adverse events (1.8% for dapagliflozin vs. 0% for placebo).
One event of pyelonephritis was observed in the dapagliflozin group. One
or more serious adverse events occurred in 0.9% of patients in the
dapagliflozin group and 5.5% of patients in the placebo group. The
overall profile of dapagliflozin in this trial is consistent with those
seen in Phase II and III clinical trials for dapagliflozin.
Study Design
This 24-week Phase III, randomized, double-blind, placebo-controlled
study with an ongoing 28-week extension is designed to evaluate the
efficacy and safety of dapagliflozin in patients with type 2 diabetes
with inadequate glycemic control on combination therapy with metformin
plus sulfonylurea. The primary endpoint is mean change in HbA1c from
baseline to week 24. Secondary endpoints include mean change from
baseline to week 24 in FPG and total body weight, proportion of patients
achieving HbA1c levels of < 7.0% at week 24 and change in SBP from
baseline to week 8.
The study includes 216 adult patients with type 2 diabetes (aged ≥ 18
years) with inadequate glycemic control (HbA1c ≥ 7.0% and ≤ 10.5%)
receiving metformin (≥ 1500 mg QD) and a maximum tolerated dose of
sulfonylurea (at least half the maximum label dose for ≥ 8 weeks).
Patients were randomized to receive dapagliflozin 10 mg (n = 108) or
placebo (n = 108) for 24 weeks.
About SGLT2 Inhibition
The kidney plays an important role in maintaining normal glucose balance
by filtering and reabsorbing glucose from circulation. SGLT2, a
sodium-glucose cotransporter found predominantly in the kidney, is
responsible for the majority of glucose reabsorption. In patients with
type 2 diabetes, the capacity of the kidney to reabsorb glucose is
increased by approximately 20%, further exacerbating the hyperglycemia
associated with the disease. Selective inhibition of SGLT2 reduces the
reabsorption of excess glucose and enables its removal via the urine.
About Diabetes
In 2012, diabetes was estimated to affect more than 370 million people
worldwide. The prevalence of diabetes is projected to reach more than
550 million by 2030. Type 2 diabetes accounts for approximately 90% to
95% of all cases of diagnosed diabetes in adults. Type 2 diabetes is a
chronic disease characterized by insulin resistance and dysfunction of
beta cells in the pancreas, leading to elevated glucose levels. Over
time, this sustained hyperglycemia contributes to further progression of
the disease. Significant unmet needs still exist, as many patients
remain inadequately controlled on their current glucose-lowering regimen.
About the AstraZeneca/Bristol-Myers Squibb Diabetes Alliance
Dedicated to addressing the global burden of diabetes by advancing
individualized patient care, AstraZeneca and Bristol-Myers Squibb are
working in collaboration to research, develop and commercialize a
versatile portfolio of innovative treatment options for diabetes and
related metabolic disorders that aim to provide treatment effects beyond
glucose control. Find out more about the Alliance and our commitment to
meeting the needs of health care professionals and people with diabetes
at www.astrazeneca.com
or www.bms.com.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of cardiovascular,
metabolic, respiratory, inflammation, autoimmune, oncology, infection
and neuroscience diseases. AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
For more information please visit: www.astrazeneca.com.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information about
Bristol-Myers Squibb, visit www.bms.com
or follow us on Twitter at http://twitter.com/bmsnews.
AstraZeneca Cautionary Statement Regarding Forward-Looking Statement
In order, among other things, to utilise the 'safe harbour'
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are providing the following cautionary statement: This press release
contains certain forward-looking statements with respect to the
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we believe our expectations are based on reasonable assumptions, any
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effect on future commercial prospects; and the impact of increasing
implementation and enforcement of more stringent anti-bribery and
anti-corruption legislation. Nothing in this press release should be
construed as a profit forecast.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding product development. Such forward-looking statements are based
on current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect Bristol-Myers Squibb's
business, particularly those identified in the cautionary factors
discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the
year ended December 31, 2012, in our Quarterly Reports on Form 10-Q and
our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no
obligation to publicly update any forward-looking statement, whether as
a result of new information, future events or otherwise.
Copyright Business Wire 2013