AstraZeneca and Bristol-Myers Squibb Announce Top Line Results for SAVOR-TIMI-53 Cardiovascular Outcomes Trial of Onglyza®

  AstraZeneca and Bristol-Myers Squibb Announce Top Line Results for
  SAVOR-TIMI-53 Cardiovascular Outcomes Trial of Onglyza® (saxagliptin)

Business Wire

PRINCETON, N.J. & WILMINGTON, Del. -- June 19, 2013

Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) today
announced top line results of the Phase 4 SAVOR-TIMI-53 (Saxagliptin
Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus)
clinical trial of Onglyza ^® (saxagliptin). In this study of adult patients
with type 2 diabetes with either a history of established cardiovascular
disease or multiple risk factors, Onglyza met the primary safety objective of
non-inferiority, and did not meet the primary efficacy objective of
superiority, for a composite endpoint of cardiovascular death, non-fatal
myocardial infarction or non-fatal ischaemic stroke, when added to a patient’s
current standard of care (with or without other anti-diabetic therapies), as
compared to placebo.

These preliminary SAVOR-TIMI-53 data are being analyzed and the study results
will be submitted to the European Society of Cardiology (ESC) for potential
presentation at the ESC Congress in September.

About Onglyza^® (saxagliptin)

Onglyza is indicated as an adjunct to diet and exercise to improve glycemic
(blood sugar) control in adults with type 2 diabetes mellitus in multiple
clinical settings. Onglyza should not be used for the treatment of patients
with type 1 diabetes mellitus or diabetic ketoacidosis (increased levels of
ketones in the blood or urine), as it would not be effective in these
settings. Onglyza has not been studied in patients with a history of
pancreatitis.

Onglyza is contraindicated in patients with a history of a serious
hypersensitivity reaction to Onglyza (e.g., anaphylaxis, angioedema or
exfoliative skin conditions). There have been post-marketing reports of acute
pancreatitis and serious hypersensitivity reactions in patients taking
Onglyza. If pancreatitis or a serious hypersensitivity reaction is suspected,
promptly discontinue Onglyza and institute appropriate medical treatment. It
is unknown whether patients with a history of pancreatitis are at an increased
risk for development of pancreatitis while using Onglyza.

When Onglyza was used in combination with a sulfonylurea or with insulin (two
medications known to cause hypoglycemia), the incidence of confirmed
hypoglycemia was increased over that of placebo used in combination with a
sulfonylurea or with insulin. Therefore, a lower dose of the insulin
secretagogue or insulin may be required to minimize the risk of hypoglycemia
when used in combination with Onglyza.

As of June 2013, Onglyza has been submitted for regulatory review in 95
countries and is approved in 86 countries including those in the European
Union, the United States, Canada, Mexico, India, Brazil and China.

Indication and Limitations of Use for ONGLYZA^® (saxagliptin)

ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic
control in adults with type 2 diabetes mellitus in multiple clinical settings.

ONGLYZA should not be used for the treatment of type 1 diabetes mellitus or
diabetic ketoacidosis.

ONGLYZA has not been studied in patients with a history of pancreatitis.

Important Safety Information for ONGLYZA

Contraindications

  *History of a serious hypersensitivity reaction to ONGLYZA (eg,
    anaphylaxis, angioedema, or exfoliative skin conditions)

Warnings and Precautions

  *Pancreatitis: There have been postmarketing reports of acute pancreatitis
    in patients taking ONGLYZA. After initiating ONGLYZA, observe patients
    carefully for signs and symptoms of pancreatitis. If pancreatitis is
    suspected, promptly discontinue ONGLYZA and initiate appropriate
    management. It is unknown whether patients with a history of pancreatitis
    are at increased risk of developing pancreatitis while using ONGLYZA.
  *Hypoglycemia with Concomitant Use of Sulfonylurea or Insulin: When ONGLYZA
    was used in combination with a sulfonylurea or with insulin, medications
    known to cause hypoglycemia, the incidence of confirmed hypoglycemia was
    increased over that of placebo used in combination with a sulfonylurea or
    with insulin. Therefore, a lower dose of the insulin secretagogue or
    insulin may be required to minimize the risk of hypoglycemia when used in
    combination with ONGLYZA.
  *Hypersensitivity Reactions: There have been postmarketing reports of
    serious hypersensitivity reactions in patients treated with ONGLYZA,
    including anaphylaxis, angioedema, and exfoliative skin conditions. Onset
    of these reactions occurred within the first 3 months after initiation of
    treatment with ONGLYZA, with some reports occurring after the first dose.
    If a serious hypersensitivity reaction is suspected, discontinue ONGLYZA,
    assess for other potential causes for the event, and institute alternative
    treatment for diabetes. Use caution in patients with a history of
    angioedema to another DPP-4 inhibitor as it is unknown whether they will
    be predisposed to angioedema 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

  *Most common adverse reactions reported in ≥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.
  *Confirmed hypoglycemia was reported more commonly in patients treated with
    ONGLYZA 2.5 mg and ONGLYZA 5 mg compared to placebo in the add-on to
    glyburide trial (2.4%, 0.8% and 0.7%, respectively), with ONGLYZA 5 mg
    compared to placebo in the add-on to insulin (with or without metformin)
    trial (5.3% and 3.3%, respectively),with ONGLYZA 2.5 mg compared to
    placebo in the renal impairment trial (4.7% and 3.5%, respectively), and
    with ONGLYZA 5 mg compared to placebo in the add-on to metformin plus
    sulfonylurea trial (1.6% and 0.0%, respectively).

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 (eg, atazanavir, clarithromycin, indinavir,
itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and
telithromycin).

Use in Specific Populations

  *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] ≤50
    mL/min). ONGLYZA 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.

Please click here for full U.S. Prescribing Information and Medication Guide
for ONGLYZA (saxagliptin).

About Type 2 Diabetes

At the end of 2012, diabetes was estimated to affect more than 370 million
people aged 20-79 worldwide. Because of the aging population and the growing
trend of obesity, the prevalence of diabetes is projected to reach more than
550 million by 2030. Type 2 diabetes accounts for approximately 90 to 95% of
all cases of diagnosed diabetes in adults. Type 2 diabetes is a chronic
disease characterized by insulin resistance and dysfunction of beta cells in
the pancreas, which decreases insulin sensitivity and secretion, leading to
elevated glucose levels.Over time, this sustained hyperglycemia contributes
to worsening insulin resistance and further beta cell dysfunction. Significant
unmet needs still exist, as many patients remain inadequately controlled on
their current glucose-lowering regimen.

The major cause of death and complications in patients with type 2 diabetes is
cardiovascular disease. As many as 80% of patients with type 2 diabetes will
develop and possibly die from a cardiovascular event.

About SAVOR

SAVOR-TIMI-53 was a randomized, double-blind, placebo-controlled trial that
involved 16,500 patients in 25 countries with type 2 diabetes who had a
history of established cardiovascular disease or multiple risk factors, with
or without renal impairment. SAVOR was led by the academic research
organizations TIMI Study Group and Hadassah University Medical Center and
conducted at over 700 sites worldwide.

AstraZeneca / Bristol-Myers Squibb Diabetes Alliance

Dedicated to addressing the global burden of diabetes by advancing
individualized patient care, AstraZeneca and Bristol-Myers Squibb are working
in collaboration to research, develop and commercialize a versatile portfolio
of innovative treatment options for diabetes and related metabolic disorders
that aim to provide treatment effects beyond glucose control. Find out more
about the Alliance and our commitment to meeting the needs of health care
professionals and people with diabetes at www.astrazeneca.com or www.bms.com.

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, please visit http://www.bms.com
or follow us on Twitter at http://twitter.com/bmsnews.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialisation of prescription
medicines, primarily for the treatment of cardiovascular, metabolic,
respiratory, inflammation, autoimmune, oncology, infection and neuroscience
diseases. AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more information
please visit: www.astrazeneca.com.

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
product development. 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. Forward-looking statements in
this 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, 2012, in our Quarterly Reports on
Form 10-Q and our 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.

AstraZeneca Cautionary Statement Regarding Forward-Looking Statements

In order, among other things, to utilise the 'safe harbour' provisions of the
US Private Securities Litigation Reform Act 1995, we are providing the
following cautionary statement: This press release contains certain
forward-looking statements with respect to the operations, performance and
financial condition of the Group. Although we believe our expectations are
based on reasonable assumptions, any forward-looking statements, by their very
nature, involve risks and uncertainties and may be influenced by factors that
could cause actual outcomes and results to be materially different from those
predicted. The forward looking statements reflect knowledge and information
available at the date of preparation of this press release and AstraZeneca
undertakes no obligation to update these forward-looking statements. We
identify the forward-looking statements by using the words 'anticipates',
'believes', 'expects', 'intends' and similar expressions in such statements.
Important factors that could cause actual results to differ materially from
those contained in forward-looking statements, certain of which are beyond our
control, include, among other things: the loss or expiration of patents,
marketing exclusivity or trade marks, or the risk of failure to obtain patent
protection; the risk of substantial adverse litigation/government
investigation claims and insufficient insurance coverage; exchange rate
fluctuations; the risk that R&D will not yield new products that achieve
commercial success; the risk that strategic alliances and acquisitions will be
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of any failure by third parties to supply materials or services; the risk of
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difficulties of obtaining and maintaining regulatory approvals for products;
the risk of failure to observe ongoing regulatory oversight; the risk that new
products do not perform as we expect; the risk of environmental liabilities;
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to successfully implement planned cost reduction measures through productivity
initiatives and restructuring programmes; the risk that regulatory approval
processes for biosimilars could have an adverse effect on future commercial
prospects; and the impact of increasing implementation and enforcement of more
stringent anti-bribery and anti-corruption legislation. Nothing in this press
release should be construed as a profit forecast.

Contact:

Media:
Bristol-Myers Squibb
Ken Dominski, 609-252-5251
ken.dominski@bms.com
or
AstraZeneca
Kirsten Evraire, 302-885-0435
kirsten.evraire@astrazeneca.com
or
Investors:
Bristol-Myers Squibb
John Elicker, 609-252-4611
john.elicker@bms.com
or
AstraZeneca
Karl Hard, 44-20-7604-8123
karl.j.hard@astrazeneca.com