Study Finds That ONGLYZA(TM) (saxagliptin) When Added to Metformin was Non-Inferior to JANUVIA (sitagliptin) When Added to Metformin in Reducing Hemoglobin (HbA1c) in Adults With Type 2 Diabetes Melli

Princeton, New Jersey and London (ots/PRNewswire) -
Results from an 18-week phase 3b study in adults with type 2 diabetes
with inadequate glycemic control on metformin therapy alone found
that the addition of treatment with ONGLYZA(TM) (saxagliptin) 5 mg
per day achieved the primary objective of demonstrating
non-inferiority compared to the addition of treatment with JANUVIA(R)
(sitagliptin) 100 mg per day in reducing HbA1c from baseline. In this
study, overall adverse events were reported at a similar rate for
individuals taking ONGLYZA 5 mg plus metformin and JANUVIA 100 mg
plus metformin. This study was submitted to the European Medicines
Agency (EMEA) as part of the Marketing Authorization Application for
ONGLYZA. Complete findings from this study will be submitted for
publication in the first half of 2010.

ONGLYZA, a dipeptidyl peptidase 4 (DPP4) inhibitor, was recently
approved by the European Commission as an adjunct to diet and
exercise to improve blood sugar (glycemic) control in adults for the
treatment of type 2 diabetes mellitus. ONGLYZA once daily can be used
in combination with commonly prescribed oral anti-diabetic
medications - metformin, sulfonylureas or thiazolidinediones (TZD) to
significantly reduce HbA1c levels. ONGLYZA has also been approved by
the U.S. Food and Drug Administration (July, 2009) as an adjunct to
diet and exercise to improve blood sugar (glycemic) control in adults
for the treatment of type 2 diabetes mellitus. ONGLYZA should not be
used for the treatment of type 1 diabetes or for the treatment of
diabetic ketoacidosis (high levels of certain acids, known as
ketones, in the blood or urine). ONGLYZA has not been studied in
combination with insulin.

"We are pleased with the findings from this study, which support
that the addition of ONGLYZA to metformin lowers HbA1c in adults with
inadequate glycemic control despite treatment with metformin," said
Andre Scheen, MD, Head of the Division of Diabetes, Nutrition and
Metabolic Disorders and Clinical Pharmacology Unit, Academic
Hospital, Liège, Belgium.

About the Study

This study was an 18-week international, multicenter, randomized,
parallel-group, double-blind, active-controlled phase 3b study of 801
adults with type 2 diabetes (ages 22-87) whose HbA1c was greater than
6.5 percent and less than or equal to 10 percent at baseline. The
study was designed to evaluate the efficacy and safety of ONGLYZA
(saxagliptin) 5 mg and JANUVIA 100 mg in addition to metformin in
adults with type 2 diabetes who did not attain adequate glycemic
control on metformin therapy alone. Individuals were randomized to
one of two separate treatment arms, ONGLYZA 5 mg once daily plus
open-label metformin (n=403, baseline HbA1c = 7.68) or JANUVIA 100 mg
once daily plus open-label metformin (n=398, baseline HbA1c = 7.69).
The primary endpoint of the study was to assess if the change from
baseline in HbA1c achieved with ONGLYZA 5 mg per day was non-inferior
(defined in the study protocol as a treatment group numerical
difference in the HbA1c reduction of less than 0.3 for the upper
limit of the confidence interval [CI]) to JANUVIA 100 mg per day when
both were added to a stable dose of metformin, 1500 mg or higher.

Study Results

In the primary analysis of individuals who completed the study
and complied with study procedures, ONGLYZA 5 mg per day achieved an
adjusted mean change from baseline in HbA1c of -0.52 percent,
compared to -0.62 percent for subjects taking JANUVIA 100 mg per day.
Results of the study demonstrated that therapy with ONGLYZA 5 mg was
non-inferior to JANUVIA 100 mg when added to metformin (difference in
adjusted mean change from baseline vs. Januvia plus metformin 0.09
percent, 95 percent CI -0.01 to 0.20). Non-inferiority of ONGLYZA to
JANUVIA was also demonstrated in a confirmatory analysis of all
individuals receiving study treatment for whom a change from baseline
in HbA1c could be calculated.

In the study, ONGLYZA 5 mg added to metformin demonstrated a
safety profile similar to JANUVIA 100 mg added to metformin. The
number of individuals experiencing adverse events or serious adverse
events after 18 weeks was similar between the two treatment groups:
(adverse events: 47.1 percent for ONGLYZA 5 mg plus metformin, 47.2
percent for JANUVIA 100 mg plus metformin; serious adverse events:
1.7 percent for ONGLYZA 5 mg plus metformin, 1.3 percent for JANUVIA
100 mg plus metformin). A total of 9 patients discontinued in each
treatment arm due to an adverse event. Two patients (0.5 percent) in
the ONGLYZA plus metformin arm discontinued treatment due to a
serious adverse event. The number of individuals with any
hypoglycemic event was similar between the two treatment groups (3.2
percent for ONGLYZA (saxagliptin) 5 mg plus metformin, 2.8 percent
for JANUVIA plus metformin). The most common adverse events (greater
than 5 percent in at least one study group) reported with ONGLYZA 5
mg plus metformin vs. JANUVIA plus metformin were influenza (5.7
percent vs. 5.8 percent, respectively) and urinary tract infection
(5.7 percent vs. 5.3 percent, respectively).

To conclude, the study achieved its primary endpoint -
demonstrating that treatment with ONGLYZA 5 mg plus metformin was
non-inferior compared to treatment with JANUVIA 100 mg plus metformin
as measured by a change from baseline in HbA1c. Treatment with
ONGLYZA 5 mg plus metformin had a safety profile similar to JANUVIA
100 mg plus metformin.

Background On Previously Presented Studies of ONGLYZA When Used
In Combination With Metformin

ONGLYZA was studied extensively with metformin, the most
commonly-prescribed oral anti-diabetic medication. Two previously
reported studies demonstrated that ONGLYZA, when used in combination
with metformin, effectively lowered HbA1c, fasting plasma glucose and
postprandial glucose, three key measures of glycemic control. In
adult patients inadequately controlled on metformin, the addition of
ONGLYZA 2.5 mg (n=192, baseline A1C 8.1 percent) and 5 mg (n=191,
baseline A1C 8.1 percent) once daily reduced A1C levels from baseline
to Week 24 by -0.6 percent and -0.7 percent respectively for ONGLYZA
vs. +0.1 percent increase for placebo (p-values less than 0.0001 vs.
placebo, n=179, baseline A1C 8.1 percent). The reported incidence of
hypoglycemia in ONGLYZA 2.5 mg and 5 mg compared with placebo was 7.8
percent, 5.8 percent and 5 percent, respectively.

For those new to diabetes medications, the use of ONGLYZA 5 mg
with metformin (n=320, baseline A1C 9.4 percent) as initial therapy
lowered A1C from baseline to week 24 by -2.5 percent vs. -2 percent
for metformin plus placebo (p-values less than 0.0001, n=313,
baseline A1C 9.4 percent). Significantly more adult patients in the
ONGLYZA plus metformin arm achieved the American Diabetes Association
recommended A1C level of less than 7 percent than those treated with
metformin plus placebo (60 percent vs. 41 percent, respectively,
p-values less than 0.05). The reported incidence of hypoglycemia was
3.4 percent in adult patients given ONGLYZA (saxagliptin) 5 mg plus
metformin and 4 percent in adult patients given metformin alone. The
adverse reactions occurring in greater than or equal to 5 percent of
adult patients and more commonly than in adult patients treated with
metformin alone were headache (7.5 percent vs. 5.2 percent) and
nasopharyngitis (6.9 percent vs. 4 percent).

Bristol-Myers Squibb and AstraZeneca Collaboration

Bristol-Myers Squibb and AstraZeneca entered into a collaboration
in January 2007 to develop and commercialize select investigational
drugs for type 2 diabetes. These therapies address two key pathways
in managing type 2 diabetes and seek to expand the range of current
and future therapeutic options. Our collaboration is dedicated to
global patient care, improving patient outcomes and creating a new
vision for the treatment of patients living with type 2 diabetes.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company
committed to discovering, developing and delivering innovative
medicines that help patients prevail over serious diseases.

About AstraZeneca

AstraZeneca is a major international healthcare business engaged
in the research, development, manufacturing and marketing of
meaningful prescription medicines and supplier for healthcare
services. AstraZeneca is one of the world's leading pharmaceutical
companies with healthcare sales of US$ 31.6 billion and is a leader
in gastrointestinal, cardiovascular, neuroscience, respiratory,
oncology and infectious disease medicines.

ONGLYZA is a trademark of the Bristol-Myers Squibb Company.

JANUVIA is a trademark of Merck & Co. Inc.

Summary of Product Characteristics

ONGLYZA

See full prescribing information
(http://www.makealias.com/just/SmPC.pdf )

ots Originaltext: Bristol-Myers Squibb Company and AstraZeneca
Im Internet recherchierbar: http://www.presseportal.de

Contact:
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