Orlando, Florida, June 26, 2010 (ots/PRNewswire) - Bristol-Myers Squibb
Company and AstraZeneca today announced results up to 76-weeks
from a Phase 3 study of ONGLYZA(TM) (saxagliptin) as initial
combination therapy with metformin, which produced long-term
glycemic improvement [as measured by glycosylated hemoglobin level
(HbA1c)] in treatment-naive adults with type 2 diabetes mellitus
inadequately controlled on diet and exercise compared to treatment
with an investigational 10 mg dose of saxagliptin or metformin
alone. The study results also demonstrated that a higher number of
patients were able to achieve the American Diabetes Association
recommended HbA1c target of less than 7% with ONGLYZA and metformin
as initial combination therapy, compared to monotherapy of either
treatment at week 76. The initial combination of ONGLYZA and
metformin, with or without pioglitazone rescue therapy, had similar
adverse event (AE) rates compared to treatment with investigational
saxagliptin or metformin alone. Results were presented at the 70th
American Diabetes Association (ADA) Annual Scientific Sessions.
"As type 2 diabetes is a disease that needs to be actively
managed, effective treatment options are needed to help improve blood
sugar levels," said Andreas Pfutzner, MD, Chief Executive Officer,
Institute for Clinical Research and Development, Mainz, Germany.
"These data show that at 76 weeks, ONGLYZA and metformin when given
as an initial treatment provided improved HbA1c levels for adult
patients with type 2 diabetes."
ONGLYZA has been submitted for regulatory review in more than 58
countries and is approved in 43 countries, including the United
States, Canada, Mexico, 30 EU countries, Chile, India, Brazil,
Argentina and Switzerland. ONGLYZA was approved by the FDA in July
2009 and is indicated 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 used in combination with
commonly prescribed oral anti-diabetic medications - metformin,
glyburide (a sulfonylurea) or a thiazolidinedione (TZD),
(pioglitazone or rosiglitazone) - or as a monotherapy statistically
significantly reduced HbA1c levels. 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 (saxagliptin) has not been studied in
combination with insulin.
About the Study: Saxagliptin In Combination with Metformin up to
The objectives of the study were to assess the long-term efficacy
and tolerability of ONGLYZA plus metformin and an investigational
dose of saxagliptin plus metformin as initial combination therapy
compared to an investigational dose of saxagliptin or metformin
alone. The study assessed the change from baseline in HbA1c and the
proportion of individuals achieving the American Diabetes Association
recommended HbA1c target of less than 7%.
The study was a multicenter, randomized, double-blind,
active-controlled, 24 week short-term study of 1,306 patients
followed by a 52 week long-term extension period, which included
1,103 patients with type 2 diabetes (ages 18-77). Patients were
required to be treatment naive and have screening HbA1c levels of
greater than or equal to 8% and less than or equal to 12% to enter
the study. After a one-week placebo lead-in phase, individuals were
randomized to one of four separate treatment groups: ONGLYZA 5 mg +
metformin 500 mg (n=320), an investigational dose of saxagliptin 10
mg + metformin 500 mg (n=323) or saxagliptin 10 mg + placebo (n=335),
or metformin 500 mg + placebo (n=328), given daily. In the treatment
groups which included metformin, the daily metformin dose could be
increased to a maximum of 2,000 mg based on pre-specified glycemic
criteria. Patients whose HbA1c exceeded predetermined levels during
the study period received pioglitazone therapy and were eligible to
enter directly into the long-term extension period.
A total of 1,240 patients, including 612 who remained in the
study without requiring rescue therapy through week 76, were included
in a repeated measures analysis of HbA1c change from baseline. After
76 weeks, individuals in the ONGLYZA + metformin treatment groups
demonstrated a greater adjusted mean change in HbA1c from baseline:
-2.31% for ONGLYZA 5 mg + metformin group (n=303; baseline HbA1c
9.41%) and -2.33% for investigational saxagliptin 10 mg + metformin
group (n= 313; baseline HbA1c 9.54%), compared to -1.55% for
saxagliptin 10 mg + placebo (n= 316; baseline HbA1c 9.61%) and -1.79%
for metformin + placebo (n= 308; baseline HbA1c 9.42%).
A greater percentage of individuals treated with ONGLYZA
(saxagliptin) in combination with metformin achieved HbA1c of less
than 7% after 76 weeks: 51.1% for ONGLYZA 5 mg + metformin and 50.8%
in the investigational saxagliptin 10 mg + metformin, compared to
25.0% for saxagliptin 10 mg + placebo and 34.7% for metformin +
No attenuation of the reduction in three-hour postprandial
glucose OGTT (oral glucose tolerance test) as measured by the area
under the curve was apparent between weeks 24 and 76 for the ONGLYZA
+ metformin groups; partial attenuation did occur in both monotherapy
groups. The overall proportion of individuals requiring rescue or
discontinuation for lack of efficacy by week 76 was lower in the
ONGLYZA 5 mg + metformin group (23.1%) and investigational
saxagliptin 10 mg + metformin group (26.0%) versus the saxagliptin 10
mg + placebo (47.2%) and metformin + placebo (34.1%) groups of the
The percentage of patients with reported adverse events was
similar across all treatment groups. Adverse event rates were as
follows: 65.9% for ONGLYZA 5 mg + metformin, 68.4% for
investigational saxagliptin 10 mg + metformin, 66.3% for saxagliptin
10 mg + placebo, 68.3% for metformin + placebo.
The occurrence of confirmed hypoglycemia (symptoms of
hypoglycemia with a fingerstick glucose less than or equal to 50
mg/dL) was: three cases (0.9 %) in the investigational saxagliptin 10
mg + metformin group and two cases (0.6%) in the metformin + placebo
group, with no cases of confirmed hypoglycemia in the ONGLYZA 5 mg +
metformin or the saxagliptin 10 mg + placebo groups.
IMPORTANT INFORMATION ABOUT ONGLYZA
Indication and Important Limitations of Use
ONGLYZA is indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes mellitus.
ONGLYZA should not be used for the treatment of type 1 diabetes
mellitus or diabetic ketoacidosis.
ONGLYZA (saxagliptin) has not been studied in combination with
Important Safety Information
@@start.t1@@ - Use with Medications Known to Cause Hypoglycemia: Insulin
secretagogues, such as sulfonylureas, cause hypoglycemia. Therefore, a
lower dose of the insulin secretagogue may be required to reduce the
risk of hypoglycemia when used in combination with ONGLYZA.
- Macrovascular Outcomes: There have been no clinical studies
establishing conclusive evidence of macrovascular risk reduction with
ONGLYZA or any other antidiabetic drug.@@end@@
Most common adverse reactions (regardless of investigator
assessment of causality) reported in greater than or equal to 5% of
patients treated with ONGLYZA and more commonly than in patients
treated with control were upper respiratory tract infection (7.7%,
7.6%), headache (7.5%, 5.2%), nasopharyngitis (6.9%, 4.0%) and
urinary tract infection (6.8%, 6.1%). When used as add-on
combination therapy with a thiazolidinedione, the incidence of
peripheral edema for ONGLYZA 2.5 mg, 5 mg, and placebo was 3.1%,
8.1% and 4.3%, respectively.
Laboratory Tests: There was a dose-related mean decrease in
absolute lymphocyte count observed with ONGLYZA.
Drug Interactions: Because ketoconazole, a strong CYP3A4/5
inhibitor, increased saxagliptin exposure, the dose of ONGLYZA should
be limited to 2.5 mg when coadministered with a strong CYP3A4/5
inhibitor (e.g., atazanavir, clarithromycin, indinavir, itraconazole,
ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and
Patients with Renal Impairment: The dose of ONGLYZA is 2.5 mg
once daily for patients with moderate or severe renal impairment, or
with end-stage renal disease requiring hemodialysis (creatinine
clearance [CrCl] less than or equal to 50 mL/min). ONGLYZA
(saxagliptin) should be administered following hemodialysis. ONGLYZA
has not been studied in patients undergoing peritoneal dialysis.
Assessment of renal function is recommended prior to initiation of
ONGLYZA and periodically thereafter.
Pregnant and Nursing Women: There are no adequate and
well-controlled studies in pregnant women. ONGLYZA, like other
antidiabetic medications, should be used during pregnancy only if
clearly needed. It is not known whether saxagliptin is secreted in
human milk. Because many drugs are secreted in human milk, caution
should be exercised when ONGLYZA is administered to a nursing woman.
Pediatric Patients: Safety and effectiveness of ONGLYZA in
pediatric patients have not been established.
U.S. Full Prescribing Information is available at www.bms.com. ;
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
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.
For more information about AstraZeneca in the US or our AZ&Me(TM)
Prescription Savings programs, please visit:
http://www.astrazeneca-us.com or call +1-800-AZandMe (292-6363).
ONGLYZA is a trademark of the Bristol-Myers Squibb Company.
ots Originaltext: Bristol-Myers Squibb and AstraZeneca
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