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Bristol-Myers Squibb and AstraZeneca

New Data for Investigational Diabetes Drug Saxagliptin Demonstrates Potential for Type 2 Diabetes Treatment

Rome (ots/PRNewswire)

  • FOR EUROPEAN MEDICAL MEDIA ONLY
  • New Data Presented for the First Time at EASD 2008
  • Saxagliptin With Metformin as Initial Combination Therapy Lowered A1C
  • Improvements Demonstrated Across Key Measures of Glucose Control Studied in Treatment-Naïve People With Type 2 Diabetes
  • For Presentation Time and Detailed Study Information Please Refer to Notes to Editors
Results from a 24-week Phase III study presented at the 44th
European Association for the Study of Diabetes Annual Meeting
demonstrated that saxagliptin, an investigational selective inhibitor
with extended binding to the dipeptidyl peptidase-4 (DPP-4) enzyme,
in development by Bristol-Myers Squibb Company (NYSE: BMY) and
AstraZeneca, when used in combination with metformin as an initial
therapy, produced reductions across all key measures of glucose
control studied (glycosylated hemoglobin level (A1C), fasting plasma
glucose (FPG) and postprandial glucose (PPG)) in treatment-naïve
people with inadequately controlled type 2 diabetes, compared with
monotherapy with saxagliptin or metformin. The initial combination of
saxagliptin and metformin was well tolerated during the course of the
study, and more people were able to achieve target A1C of less than 7
percent, compared with monotherapy with saxagliptin or metformin.
"With these new data, Phase III studies for saxagliptin have
demonstrated that saxagliptin improved key markers for glucose
control when given with standard therapies for type 2 diabetes and as
a monotherapy," said Professor Anthony Barnett, University of
Birmingham and Heart of England NHS Foundation Trust. "The clinical
trial programme for saxagliptin evaluated more than 5,000
individuals, including more than 4,000 who were given saxagliptin."
The companies submitted a New Drug Application to the U.S. Food &
Drug Administration (FDA) on 30th June, which has been officially
filed by the FDA, and a Marketing Authorization Applic ation to the
European Medicines Agency (EMEA) on 1st July, which has been accepted
for review by the Agency. The submissions are based on data from a
comprehensive clinical trial programme conducted in addition to
standard therapies, as well as in treatment-naïve patients as a
monotherapy. The clinical trial programme included studies that
evaluated the drug at up to 80 times the proposed usual clinical dose
of 5 mg, once daily. The six core Phase III trials assessing the
efficacy and safety profile of saxagliptin involved more than 4,000
patients, including 3,000 who were treated with saxagliptin.
Notes to Editors
Study results in detail:
Phase III - Oral Presentation: Initial combination therapy with
saxagliptin and metformin improves glycemic control compared with
either monotherapy alone in drug-naïve patients with type 2 diabetes
Presentation: 9th September 2008, 10h45 - 12h15 Central European
Time (CET)
The study was designed to assess saxagliptin as an initial
combination therapy with metformin versus each agent alone. The data
represent findings from a 24-week, randomized, double-blind,
active-controlled study of 1,306 people with type 2 diabetes (ages
18-77) who were treatment naïve and whose A1C level was greater than
or equal to 8 percent and less than or equal to 12 percent. After a
one-week placebo lead-in phase, individuals were randomized to one of
four separate treatment arms: saxagliptin 5 mg + metformin 500 mg
(n=320), saxagliptin 10 mg + metformin 500 mg (n=323), saxagliptin 10
mg + placebo (n=335) or metformin 500 mg + placebo (n=328), given
daily. From week 1 to week 5, in the saxagliptin 5 mg + metformin,
saxagliptin 10 mg + metformin and metformin + placebo treatment arms,
metformin was up-titrated weekly in 500 mg increments, as tolerated,
to a maximum total daily dose of 2,000 mg, based on levels of FPG (a
measure of a person's blood glucose after at least eight hours of
fasting(1)).
The primary endpoint of the study was the change from baseline to
week 24 in A1C. The secondary endpoints included the proportion of
individuals achieving the American Diabetes Association recommended
A1C target of less than 7 percent, the proportion of individuals
achieving the International Diabetes Federation recommended A1C
target of less than or equal to 6.5 percent and changes from baseline
in FPG and PPG (a measure of a person's blood glucose after a meal),
measured during an oral glucose tolerance test (OGTT).
Study results
After 24 weeks, individuals in the saxagliptin + metformin
treatment arms demonstrated an adjusted mean change in A1C from
baseline of -2.5 percent for saxagliptin 5 mg + metformin and -2.5
percent for saxagliptin 10 mg + metformin, compared with -1.7 percent
for saxagliptin 10 mg + placebo and -2.0 percent for metformin +
placebo (p-value less than 0.0001 for both treatment arms).
A greater percentage of individuals treated with saxagliptin in
combination with metformin achieved A1C of less than 7 percent: 60.3
percent for saxagliptin 5 mg + metformin and 59.7 percent for
saxagliptin 10 mg + metformin, compared with 32.2 percent for
saxagliptin 10 mg + placebo and 41.1 percent for metformin + placebo
(p-value less than 0.0001 for both treatment arms). A greater
percentage of individuals treated with saxagliptin in combination
with metformin also achieved A1C of less than or equal to 6.5
percent: 45.3 percent for saxagliptin 5 mg + metformin and 40.6
percent for saxagliptin 10 mg + metformin, compared with 20.3 percent
for saxagliptin 10 mg + placebo and 29.0 percent for metformin +
placebo (p-value less than or equal to 0.0026 for both treatment
arms).
Individuals treated with saxagliptin in combination with
metformin demonstrated an adjusted mean change in FPG from baseline:
-60 mg/dL for saxagliptin 5 mg + metformin and -62 mg/dL for
saxagliptin 10 mg + metformin, compared with -31 mg/dL for
saxagliptin 10 mg + placebo and -47 mg/dL for metformin + placebo
(p-value less than or equal to 0.0002 for both treatment arms). The
two saxagliptin + metformin treatment arms also demonstrated adjusted
mean decreases in PPG from baseline, compared with either
monotherapy.
Throughout 24 weeks, the incidence of adverse events was: 55.3
percent for saxagliptin 5 mg + metformin, 57.3 percent for
saxagliptin 10 mg + metformin, 53.4 percent for saxagliptin 10 mg +
placebo and 58.5 percent for metformin + placebo. The percentages of
the most commonly reported (greater than or equal to 5 percent)
adverse events for saxagliptin from the saxagliptin 5 mg + metformin,
saxagliptin 10 mg + metformin, saxagliptin 10 mg + placebo and
metformin + placebo treatment arms, respectively, were:
nasopharyngitis (6.9, 2.5, 4.2, 4.0), headache (7.5, 9.9, 6.3, 5.2),
diarrhoea (6.9, 9.6, 3.0, 7.3) and hypertension (4.7, 5.3, 4.5, 3.4).
The reported hypoglycemic events were: 3.4 percent for
saxagliptin 5 mg + metformin, 5.0 percent for saxagliptin 10 mg +
metformin, 1.5 percent for saxagliptin 10 mg + placebo and 4.0
percent for metformin + placebo. The occurrence of confirmed
hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose
less than or equal to 50 mg/dL) was: two cases (0.6 percent) in the
saxagliptin 10 mg + metformin group and one case (0.3 percent) in the
metformin + placebo monotherapy group, with no cases of confirmed
hypoglycemia in the saxagliptin 5 mg + metformin or the saxagliptin
10 mg + placebo groups.
Similar reductions in weight were seen across all treatment
groups. Mean change from baseline in body weight at week 24 was: -1.8
kg for saxagliptin 5 mg + metformin, -1.4 kg for saxagliptin 10 mg +
metformin, -1.1 kg for saxagliptin 10 mg + placebo and -1.6 kg for
metformin + placebo.
About saxagliptin
Saxagliptin is an investigational DPP-4 inhibitor under joint
development by Bristol-Myers Squibb and AstraZeneca for the treatment
of type 2 diabetes. Saxagliptin is being studied in clinical trials
as a once-daily therapy to determine its efficacy and safety profile.
Saxagliptin was specifically designed to be a selective inhibitor
with extended binding to the DPP-4 enzyme, with dual routes of
clearance.
Saxagliptin Phase III data have previously been presented as a
monotherapy, as well as in combination with metformin, sulphonylureas
and thiazolidinediones, commonly prescribed oral anti-diabetic
medications. The overall clinical development programme included more
than 5,000 individuals, more than 4,000 of whom were given
saxagliptin.
About DPP-4 inhibitors
DPP-4 inhibitors are a class of compounds that work by affecting
the action of natural hormones in the body called incretins.
Incretins decrease elevated blood sugar levels (glucose) by
increasing the body's use of sugar, mainly through increasing insulin
production in the pancreas, and by reducing the liver's production of
glucose.
About type 2 diabetes
Diabetes (diabetes mellitus) is a chronic disease in which the
body does not produce or properly use insulin. Insulin is a hormone
that is needed to convert sugar, starches (carbohydrates) and other
nutrients into energy needed for daily life. The cause of diabetes
continues to be investigated, and both genetic and environmental
factors such as obesity and lack of exercise appear to play a
role.(2a) Diabetes is associated with long-term complications that
affect almost every part of the body. The disease may lead to
blindness, heart and blood vessel disease, stroke, kidney failure,
amputations, and nerve damage.(3a)
There are two primary underlying causes associated with type 2
diabetes: the body does not produce enough insulin (insulin
deficiency), or the cells ignore the insulin (insulin
resistance).(3b) Symptoms of type 2 diabetes develop gradually, and
their onset is not as sudden as in type 1 diabetes. Symptoms may
include fatigue, frequent urination, increased thirst and hunger,
weight loss, blurred vision, and slow healing of wounds or sores.
Some people, however, have no symptoms.(4b)
Type 2 diabetes is most often associated with older age, obesity,
family history of diabetes, previous history of gestational diabetes,
physical inactivity and certain ethnicities.(4c) People with type 2
diabetes often are characterized with: insulin resistance, abdominal
obesity, a sedentary lifestyle, having low HDL-C ("good") cholesterol
levels and high triglyceride levels and hypertension.(4)
Type 2 diabetes accounts for approximately 90 to 95 percent of
all diabetes.(4d) This equates to roughly 221 million people with
type 2 diabetes globally,(5,4d) and 21.2 million people in the United
States alone.(3a,4d)
The American Diabetes Association recommends a hemoglobin A1C
measurement of less than 7 percent(6) for most people with type 2
diabetes. The International Diabetes Federation recommends an A1C of
less than or equal to 6.5 percent(7) for most people with type 2
diabetes. Hemoglobin A1C is a measurement of a person's average blood
glucose level during a two-to-three month period and is considered an
important marker of long-term glucose control.(8) Other important
markers for type 2 diabetes include fasting plasma glucose, a measure
of a person's blood glucose after at least 8 hours of fasting and
postprandial glucose, a measure of a person's blood glucose after a
meal.
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
commercialise two investigational drugs for type 2 diabetes -
saxagliptin and dapagliflozin. 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 extend and enhance human life.
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 the research, development and commercialization of
products. 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 the product described in
this release will receive regulatory approval. There can be no
assurance that if approved, the product will be commercially
successful. Forward-looking statements in the 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, 2007, its Quarterly
Reports on Form 10-Q, and 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.
About AstraZeneca
AstraZeneca is a major international healthcare business engaged
in research, development, manufacturing and marketing of prescription
pharmaceuticals and supplier for healthcare services. AstraZeneca is
one of the world's leading pharmaceutical companies with healthcare
sales of US $29.55 billion and is a leader in gastrointestinal,
cardiovascular, neuroscience, respiratory, oncology and infection
product sales. AstraZeneca is listed in the Dow Jones Sustainability
Index (Global) as well as the FTSE4Good Index.
(1) National Institute of Diabetes and Digestive and Kidney
Disorders, Diagnosis of Diabetes,
http://diabetes.niddk.nih.gov/dm/pubs/diagnosis/diagnosis.pdf;
accessed June 2, 2008
(2) American Diabetes Association. All About Diabetes.
a http://www.diabetes.org/about-diabetes.jsp; accessed Aug. 7,
2008
b http://www.diabetes.org/type-2-diabetes.jsp; accessed Aug. 7,
2008
(3) National Diabetes Information Clearinghouse. National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health. http://diabetes.niddk.nih.gov; accessed Aug. 7,
2008.
a http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#scope;
accessed Aug. 7, 2008
b http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#types;
Type 2 Diabetes section; accessed Aug. 7, 2008
c http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#types;
Type 2 Diabetes section; accessed Aug. 7, 2008
d http://diabetes.niddk.nih.gov/dm/pubs/overview/index.htm#types;
Type 2 Diabetes section; accessed Aug. 7, 2008
(4) American Heart Association. Type 2 Diabetes; "Who Is At Risk
For Type 2 Diabetes" section.
http://www.americanheart.org/presenter.jhtml?identifier=3044759;
accessed Aug. 7, 2008.
(5) International Diabetes Foundation. Diabetes Atlas. Third
Edition. 2006. Page 22.
(6) American Diabetes Association, Accord Trial Questions &
Answers,
http://www.diabetes.org/for-media/pr-accord-trail-QA-020608.jsp#9;
accessed Aug. 7, 2008
(7) International Diabetes Federation, Global Guidelines for Type
2 Diabetes, Chapter 6: Glucose Control Levels, page 27. http://www.id
f.org/webdata/docs/GGT2D%2006%20Glucose%20control%20levels.pdf;
accessed Aug. 18, 2008
(8) American Diabetes Association, A1C Test,
http://www.diabetes.org/type-1-diabetes/a1c-test.jsp; accessed Aug.
7, 2008
Contacts:
    Media                        Investors
    Carmel Hogan                 John Elicker
    Bristol-Myers Squibb         Bristol-Myers Squibb
    Office: +33-1-58-83-65-55    Office: +1-212-546-3775
    Cell: +33-6-74-10-76-58       john.elicker@bms.com
     carmel.hogan@bms.com
    Jim Minnick                  Mina Blair
    AstraZeneca                  AstraZeneca
    Office: +1-302-886-5135      Office: +44-20-7304-5084
    Cell: +1-610-457-1828         mina.blair@astrazeneca.com
     jim.minnick@astrazeneca.com

Contact:

Contacts: Media - Carmel Hogan, Bristol-Myers Squibb, Office:
+33-1-58-83-65-55, Cell: +33-6-74-10-76-58, carmel.hogan@bms.com; Jim
Minnick, AstraZeneca, Office: +1-302-886-5135, Cell: +1-610-457-1828,
jim.minnick@astrazeneca.com; Investors - John Elicker, Bristol-Myers
Squibb, Office: +1-212-546-3775, john.elicker@bms.com; Mina Blair,
AstraZeneca, Office: +44-20-7304-5084, mina.blair@astrazeneca.com