-- Additional Findings Reported Safety & Tolerability Profile in Subjects
with Type 2 Diabetes and Healthy Subjects --
CHICAGO, June 25 /PRNewswire-FirstCall/ -- Phase III data presented
this week at the annual meeting of the American Diabetes Association
demonstrated that saxagliptin, an inhibitor of dipeptidyl-peptidase-4
(DPP-4) in development by Bristol-Myers Squibb Company (NYSE: BMY) and
AstraZeneca (NYSE: AZN), in combination with metformin, exhibited a
statistically significant improvement in glycemic control in subjects with
Type 2 diabetes compared to metformin alone through 24 weeks of treatment.
This was the first time that Phase III data for saxagliptin have been
presented in a scientific setting.
A group of 743 subjects (ages 18-77) with Type 2 diabetes whose
hemoglobin A1C level was within the range of greater than or equal to 7
percent or less than or equal to 10 percent and on a stable metformin dose
alone (1500 to 2550 mg/day) were randomized 1:1:1:1 to add-on saxagliptin
2.5 mg, 5 mg, 10 mg, or placebo once daily. The primary endpoint of the
study was the change from baseline in hemoglobin A1C levels. After 24
weeks, the subjects receiving saxagliptin+metformin demonstrated
statistically significant decreases in hemoglobin A1C levels compared to
placebo+metformin: -0.73 percent, -0.83 percent, and -0.72 percent at the
2.5 mg, 5 mg and 10 mg doses, respectively (p-value at all dosage levels
less than 0.0001 vs. placebo+metformin).
Saxagliptin+metformin also statistically significantly reduced fasting
plasma glucose (secondary endpoint) as compared to placebo+metformin: -16
mg/dL, -23 mg/dL, and -22 mg/dL for saxagliptin 2.5 mg, 5 mg and 10 mg,
respectively (p-value at all dosage levels less than 0.0001 vs.
placebo+metformin). The percentage of subjects with hemoglobin A1C less
than 7 percent at Week 24 (secondary endpoint) was 17 percent for
placebo+metformin and 37 percent, 44 percent and 44 percent for the 2.5 mg,
5 mg and 10 mg doses of saxagliptin respectively (p-value at all dosage
levels less than 0.0001 vs. placebo+metformin).
In this study, the number of subjects with investigator-reported
hypoglycemia, with or without confirmation, were: 9 on placebo+metformin,
and 15, 10 and 7, for 2.5 mg, 5 mg, and 10 mg on saxagliptin+metformin,
respectively. There was one subject with confirmed hypoglycemia in each of
the four arms (as measured by blood glucose less than or equal to 50 mg/dL
with symptoms). The most common adverse events seen in more than 5 percent
of subjects randomized to either placebo+metformin or saxagliptin+metformin
(all doses combined) were: nasopharyngitis 7.8% vs. 8.7 %, headache 7.3%
vs. 8.0%, diarrhea 11.2% vs. 7.1%, upper respiratory infection 5.0% vs.
6.6%, influenza 7.3% vs. 6.0%, and urinary tract infection 4.5% vs. 5.1%.
Phase I Studies Also Presented at 2007 American Diabetes Association
Annual Meeting
In the presentation "Safety, Tolerability, Pharmacokinetics and
Pharmacodynamics of Once-Daily Oral Doses of Saxagliptin for 2 Weeks in
Type 2 diabetic and Healthy Subjects" by David Boulton, Ph.D., Principal
Scientist, Bristol-Myers Squibb, results from two Phase I studies were
reported. Study 1 was conducted in subjects with Type 2 diabetes; Study 2
was conducted in healthy subjects. Both studies were placebo-controlled,
randomized, double-blind, sequential, multiple ascending dose studies. The
primary objective of these two studies was to assess the safety and
tolerability profiles of multiple daily oral doses of saxagliptin in
subjects with Type 2 diabetes and in healthy subjects.
Study 1 consisted of 40 subjects (ages 18-70) who had been diagnosed
with Type 2 diabetes for less than 10 years, had hemoglobin A1C in the
range of 6.5 to 9.5 percent, and fasting plasma glucose in the range
125-250 mg/dL. Participants were randomized to receive 2.5, 5, 15, 30, or
50 mg of saxagliptin or matched placebo once-daily for 14 days (3
saxagliptin, 1 placebo ratio, n=8 subjects/dose panel).
Study 2 consisted of 50 healthy subjects (ages 18-45) who were
randomized to receive 40, 100, 150, 200, 300 or 400 mg saxagliptin or
matching placebo once daily for 14 days. Within each panel, 6 subjects
received 100, 150, 200, 300 or 400 mg saxagliptin, 2 subjects received 40
mg saxagliptin and 2 subjects received matching placebo.
In both studies, there were no deaths or serious adverse events.
Additionally, no adverse events of hypoglycemia were reported by
investigators. In Study 2, one participant experienced an adverse event
(mild rash), which resulted in discontinuation from the study while taking
200 mg of saxagliptin once daily.
About Type 2 Diabetes
Type 2 diabetes is the most common form of diabetes, accounting for
approximately 90-95 percent of diabetes cases. Having Type 2 diabetes
increases the risk of many serious complications, including heart disease
or stroke, high blood pressure, amputation (particularly legs), blindness,
nerve damage, and kidney failure. The risk of stroke and the rate of deaths
due to heart disease are two to four times higher among people with
diabetes, and about 65 percent of deaths among people with diabetes are due
to heart disease and stroke.
The A1C test (also known as hemoglobin A1C) is used primarily to
monitor the glucose control of diabetics over time. The goal of those with
diabetes is to keep their blood glucose levels as close to normal as
possible. This helps to minimize the complications caused by chronically
elevated glucose levels, such as progressive damage to body organs like the
kidneys, eyes, cardiovascular system, and nerves. The A1C test gives a
picture of the average amount of glucose in the blood over the last few
months. It can help a patient and his doctor know if the measures they are
taking to control the patient's diabetes are successful or need to be
adjusted.
About Saxagliptin
Saxagliptin is an investigational drug under development by
Bristol-Myers Squibb and AstraZeneca. It is being studied as a once daily
antidiabetic in the class of dipeptidyl peptidase-4 (DPP-4) inhibitors for
the treatment of Type 2 diabetes. DPP-4 inhibitors are a class of compounds
that work by affecting the action of natural hormones in the body called
incretins. Incretins decrease blood sugar by increasing consumption of
sugar by the body, mainly through increasing insulin production in the
pancreas, and by reducing production of sugar by the liver.
Bristol-Myers Squibb and AstraZeneca Partnership
In January 2007, Bristol-Myers Squibb and AstraZeneca entered into a
collaboration to develop and commercialize saxagliptin and dapagliflozin,
two compounds under investigation by Bristol-Myers Squibb for the treatment
of diabetes. Both companies will jointly set development and commercial
strategy for the two compounds. AstraZeneca will provide funding for the
majority of currently planned development activities; additional
development activity will be funded equally.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical and related healthcare
products 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 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 development of the products described in this release will be
successful, that the products described in this release will receive
regulatory approval, or that if approved, 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, 2006, 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 the
research, development, manufacture and marketing of prescription
pharmaceuticals and the supply of healthcare services. It is one of the
world's leading pharmaceutical companies with healthcare sales of $26.47
billion and leading positions in sales of gastrointestinal, cardiovascular,
neuroscience, respiratory, oncology and infection products. AstraZeneca is
listed in the Dow Jones Sustainability Index (Global) as well as the
FTSE4Good Index.
In the United States, AstraZeneca is a $12.44 billion healthcare
business with more than 12,000 employees. For nearly three decades,
AstraZeneca has offered drug assistance programs side by side with its
medicines, and over the past five years, has provided over $3 billion in
savings to more than 1 million patients throughout the US and Puerto Rico.
AstraZeneca has been named one of the "100 Best Companies for Working
Mothers" by Working Mother magazine and is the only large pharmaceutical
company named to FORTUNE magazine's 2007 list of "100 Best Companies to
Work For." In 2006, for the fifth consecutive year, Science magazine named
AstraZeneca a "Top Employer" on its ranking of the world's most respected
biopharmaceutical employers.
AstraZeneca Forward-Looking Statement
The statements herein include forward-looking statements. By their
nature, forward-looking statements and forecasts involve risk and
uncertainty. For a discussion of those risks and uncertainties please see
the company's Annual Report/Form 20-F for 2006.
For more information about Bristol-Myers Squibb, please visit:
http://www.bms.com.
For more information about AstraZeneca, please visit:
http://www.astrazeneca-us.com.
SOURCE Bristol-Myers Squibb; AstraZeneca Partnership
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Related links:
http://www.bms.com
http://www.astrazeneca-us.com/
CONTACT:
Media, David M. Rosen of Bristol-Myers Squibb
+1-609-252-5675 or (pager) +1-866-308-4484,
david.m.rosen@bms.com, or David Albaugh of AstraZeneca,
+1-302-886-7098 or (cell) +1-609-304-3445,
david.albaugh@astrazeneca.com; Investors, John Elicker of
Bristol-Myers Squibb, +1-212-546-3775, john.elicker@bms.com, or
Mina Blair of AstraZeneca, +44-20-7304-5084,
mina.blair@astrazeneca.com
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