Dapagliflozin As Add On Therapy To Insulin Demonstrated Improved Glycemic Control In Patients With Type 2 Diabetes Inadequately Controlled With InsulinBy Bristol-myers Squibb And Astrazeneca, PRNE
Friday, June 25, 2010
Not for US Media
ORLANDO, Florida, June 26, 2010 - Results from a 24-week Phase 3 clinical
study demonstrated that the addition of the investigational drug
dapagliflozin achieved reductions in the primary endpoint, glycosylated
hemoglobin level (HbA1c), in inadequately controlled type 2 diabetes patients
who were treated with insulin (with or without oral anti-diabetes medications
(OADs)), compared to placebo plus insulin (with or without OADs). The study
also demonstrated that dapagliflozin achieved reductions in the secondary
endpoints that evaluated the change in total body weight from baseline,
change from baseline in mean daily insulin dose, and change from baseline in
fasting plasma glucose (FPG). Generally, adverse events, serious adverse
events and study discontinuations were similar across all treatment groups.
Signs, symptoms and other reports suggestive of urinary tract and genital
infections were more frequently noted in the dapagliflozin treatment arms
compared to placebo and rarely led to discontinuation. Results from the
24-week study were presented at the 70th American Diabetes Association (ADA)
Annual Scientific Sessions.
Dapagliflozin, an investigational compound, is a potential first-in-class
sodium-glucose cotransporter-2 (SGLT2) inhibitor currently in Phase 3 trials
under joint development by Bristol-Myers Squibb Company (NYSE: BMY) and
AstraZeneca (LSN, NYSE: AZN) as a once-daily oral therapy for the treatment
of adult patients with type 2 diabetes. SGLT2 inhibitors facilitate the
elimination of glucose by the kidney, which should result in lowering serum
"Many type 2 diabetes patients who are treated with insulin are not able
to achieve their blood sugar goals," said John Wilding, DM, FRCP, Professor
of Medicine and Honorary Consultant Physician, Head of Diabetes and
Endocrinology Clinical Research Unit, University Hospital Aintree (UK). "The
Phase 3 data on glycemic and weight parameters presented today suggest that
further study of dapagliflozin in this patient population is warranted."
Data from the 48 week follow-up of the same study will be presented as a
late breaker at the ADA Scientific Sessions.
About the Study
The study was a randomized, double-blind, placebo-controlled study of 800
Individuals with type 2 diabetes (ages 18 - 80) and inadequate glycemic
control whose HbA1c level was greater than or equal to 7.5% and less than or
equal to 10.5% at baseline, with a mean baseline HbA1c level of 8.5%. The
study was designed to assess the efficacy and safety of dapagliflozin in
patients with inadequately controlled type 2 diabetes receiving treatment
with a mean insulin dose of greater than or equal to 30 IU for at least 8
weeks (mean baseline dose: 77 IU per day) with or without concomitant OADs.
Individuals were equally randomized to one of four separate treatment groups:
dapagliflozin 2.5 mg (n= 202), dapagliflozin 5 mg (n= 211), dapagliflozin 10
mg (n= 194), or placebo (n= 193).
The primary endpoint of the study compared mean HbA1c change from
baseline for each dapagliflozin treatment arm compared to placebo after 24
weeks. Secondary endpoints included change in body weight from baseline,
change from baseline in mean daily insulin dose, and change from baseline in
fasting plasma glucose (FPG).
After 24 weeks, individuals receiving dapagliflozin 2.5 mg, 5 mg and 10
mg demonstrated a statistically significant adjusted mean change in HbA1c
from baseline of -0.75%, -0.82% and -0.90%, respectively, compared to -0.30%
for placebo (p-value less than or equal to 0.0001 for all treatment groups).
The study also evaluated the potential impact of dapagliflozin on total
body weight at week 24. At week 24, the study found that individuals treated
with dapagliflozin demonstrated an adjusted mean change in total body weight:
-0.98 kg for dapagliflozin 2.5 mg, -0.98 kg for dapagliflozin 5 mg and -1.67
kg for dapagliflozin 10 mg, compared to a weight gain of 0.02 kg for placebo
(p-value less than or equal to 0.0001 for all treatment groups).
Individuals treated with dapagliflozin also demonstrated a reduction in
daily insulin dose at week 24: -1.80 IU/d for dapagliflozin 2.5 mg, -0.61
IU/d for dapagliflozin 5 mg and -1.16 IU/d for dapagliflozin 10 mg, compared
to an increase of 5.08 IU/d for placebo (p-value less than or equal to 0.0001
for all treatment groups).
Individuals treated with dapagliflozin demonstrated a reduction in FPG, a
secondary endpoint, from baseline at week 24: -12.5 mg/dL for dapagliflozin
2.5 mg, -18.8 mg/dL for dapagliflozin 5 mg and -21.7 mg/dL for dapagliflozin
10 mg, compared to an increase of 3.3 mg/dL for placebo (p-value equal to
0.0008 for dapagliflozin 2.5 mg; p-value less than or equal to 0.0001 for
dapagliflozin 10 mg. (Note that due to the study testing procedure, the
p-value for dapagliflozin 5 mg could not be assessed).
Generally, adverse events, serious adverse events and study
discontinuations were similar across all treatment groups. The percentage of
patients experiencing the most common adverse events (greater than or equal
to 5 %) for dapagliflozin 2.5 mg, 5 mg 10 mg, and placebo, respectively are
as follows: nasopharyngitis: 13.9%, 13.7%, 8.7%, 11.2%; hypertension: 5.4%,
6.1%, 3.6%, 7.6%; headache: 4.0%, 4.2%, 1.0%, 7.1%; back pain: 4.5%, 1.9%,
4.6%, 5.1%; upper respiratory tract infection: 2.5%, 2.8%, 3.1%, 5.1%.
The percentage of patients with signs, symptoms and other reports
suggestive of urinary tract and genital infections were higher for the
dapagliflozin treatment arms compared to placebo. Events suggestive of
urinary tract infections were as follows: 5.9%, 7.5%, 7.7% with dapagliflozin
2.5 mg, 5 mg and 10 mg respectively, versus 2.0% with placebo. Events
suggestive of genital infections were as follows: 5.4%, 8.0%, 9.2% with
dapagliflozin 2.5 mg, 5 mg and 10 mg respectively, versus 2.0% with placebo.
Reports of hypoglycemia observed in the dapagliflozin treatment groups
compared to placebo were 55% for dapagliflozin 2.5 mg, 47.6% for
dapagliflozin 5 mg, 44.9% for dapagliflozin 10 mg and 42.1% for placebo. Of
these hypoglycemic events, 1% were major and were equally distributed across
Reductions in blood pressure were observed without associated signs of
About Type 2 Diabetes
Type 2 diabetes (diabetes mellitus) is a complex, progressive disease
characterized by elevated glucose which is frequently associated with other
co-morbidities such as obesity, hypertension and dyslipidemia. Significant
unmet needs exist as nearly half of the patients remain uncontrolled on their
current treatment regimen.
The kidneys play a key but underappreciated role in the overall
regulation of blood glucose levels in the body. Normally, in healthy
individuals, the kidneys filter a large volume of glucose and actively
reabsorb virtually all of it. Glucose reabsorption is necessary to retain
calories, but becomes counterproductive in type 2 diabetes. In patients with
type 2 diabetes who have hyperglycemia, a greater amount of glucose is
filtered and reabsorbed by the kidneys, which contributes to sustained
hyperglycemia in diabetes.
Over time, sustained hyperglycemia worsens insulin resistance and
contributes to dysfunction in the beta cells of the pancreas further
undermining control of the disease. Sustained hyperglycemia is also directly
related to diabetic microvascular complications such as blindness and may
also contribute to macrovascular complications.
About SGLT2 Inhibition
The kidney continuously filters glucose through the glomerulus; however,
nearly all of this glucose is reabsorbed. A protein called SGLT2 is
responsible for the majority of glucose reabsorption and helps the body
retain glucose for its energy requirements. For patients with diabetes,
retention of excess glucose by this pathway contributes to persistent
hyperglycemia. Suppressing the activity of SGLT2 inhibits renal-glucose
reabsorption in the body, thereby leading to the excretion of glucose in the
Bristol-Myers Squibb and AstraZeneca Collaboration
Bristol-Myers Squibb and AstraZeneca entered into a collaboration in
January 2007 to enable the companies to research, develop and commercialize
select investigational drugs for type 2 diabetes. The Bristol-Myers
Squibb/AstraZeneca Diabetes collaboration is dedicated to global patient
care, improving patient outcomes and creating a new vision for the treatment
of type 2 diabetes.
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
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. Among other risks, there can be
no guarantee that dapagliflozin will receive regulatory approval or, if
approved, that it will become a commercially successful product.
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, 2009, 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.
AstraZeneca is a global, innovation-driven biopharmaceutical business
with a primary focus on the discovery, development and commercialization of
prescription medicines. As a leader in gastrointestinal, cardiovascular,
neuroscience, respiratory and inflammation, oncology and infectious disease
medicines, AstraZeneca generated global revenues of $32.8 billion in 2009. In
the United States, AstraZeneca is a $14.8 billion healthcare business.
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Contacts: Media: Ken Dominski, Bristol-Myers Squibb, +1-609-252-5251, ken.dominski at bms.com, Jim Minnick, AstraZeneca, +1-302-885-5135, jim.minnick at astrazeneca.com. Investors: John Elicker, Bristol-Myers Squibb, +1-609-252-4611, john.elicker at bms.com; Karl Hard, AstraZeneca, +44-20-7304-5322, karl.hard at astrazeneca.com; Clive Morris, AstraZeneca, +44-20-7304-5084, clive.morris at astrazeneca.com
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