ONGLYZA(TM) (saxagliptin) With Metformin As Initial Combination Therapy Provided 76-Week Long-Term Glycemic Control In Treatment-Naive Adults With Type 2 DiabetesBy Bristol-myers Squibb And Astrazeneca, PRNE
Friday, June 25, 2010
Not for US Media
ORLANDO, Florida, June 26, 2010 - Bristol-Myers Squibb Company (NYSE: BMY)
and AstraZeneca (NYSE: AZN) 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
"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 76 Weeks
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 + placebo.
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 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 +
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 +
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 insulin.
Important Safety Information
- 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.
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 telithromycin).
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 at
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: www.astrazeneca-us.com or
call +1-800-AZandMe (292-6363).
ONGLYZA is a trademark of the Bristol-Myers Squibb Company.
Contacts: Media: Ken Dominski, Bristol-Myers Squibb, +1-609-252-5251, ken.dominski at bms.com; Corey Windett, AstraZeneca, +1-302-885-0034, corey.windett 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.j.hard at astrazeneca.com; Clive Morris, AstraZeneca, +44-20-7304-5084, clive.morris at astrazeneca.com
Tags: Bristol-myers Squibb And Astrazeneca, florida, June 26, Orlando, United States of America