Bristol-Myers Squibb Announces Long-Term Survival Results from Pooled Analysis of Yervoy® (ipilimumab) Treatment in More Than

  Bristol-Myers Squibb Announces Long-Term Survival Results from Pooled
  Analysis of Yervoy® (ipilimumab) Treatment in More Than 1,800 Patients with
  Metastatic or Locally Advanced or Unresectable Melanoma

  *In this pooled analysis of 12 studies, a plateau in the survival curve
    begins at approximately three years, with some patients followed for up to
    ten years
  *Three-year estimated survival rate of 22% observed in patients treated
    with Yervoy
  *Findings based on different doses and regimens and show consistency of
    long-term survival data for Yervoy in metastatic melanoma
  *Data presented as a late-breaker at the 2013 European Cancer Congress and
    highlighted at Congress press briefing

Business Wire

PRINCETON, N.J. -- September 27, 2013

Bristol-Myers Squibb Company (NYSE:BMY) today announced results from a pooled
analysis of survival data for 12 studies (n=1,861) in patients with metastatic
or locally advanced or unresectable melanoma who were treated with Yervoy^®
(ipilimumab) at different doses and regimens. A plateau in the survival curve
begins at approximately three years, with follow-up of up to ten years in some
patients. Approximately 22% of patients were alive at three years. The data
will be presented at the 2013 European Cancer Congress on September 28 at 1:00
p.m. CEST and were highlighted at a Congress press briefing (Abstract # 24LBA,
“Pooled analysis of long-term survival data from Phase 2 and Phase 3 trials of
ipilimumab in metastatic or locally advanced, unresectable melanoma”).

Safety data were not included in this analysis. However, safety data from
these individual studies have been reported.Overall, the types of adverse
events (AEs) attributed to Yervoy are generally mechanism
(immune)-based.Yervoy can result in severe and fatal immune-related adverse
reactions due to T-cell activation and proliferation. In these clinical
trials, adverse events associated with Yervoy were managed with
protocol-specific guidelines, including the administration of systemic
corticosteroids, dose interruption/discontinuation and/or other
immunosuppressants.

“This pooled analysis reinforces the long-term survival data seen in the
individual studies and provides additional insight into the overall survival
of metastatic melanoma patients treated with Yervoy,” said Brian Daniels,
senior vice president, Global Development and Medical Affairs. “The durability
and consistency of long-term survival observed in this analysis is encouraging
as we continue to advance the research and development of our immuno-oncology
portfolio.”

“In this analysis, approximately 26% of treatment-naïve and 20% of
previously-treated patients were alive at three years after being treated with
an ipilimumab regimen,” said F. Stephen Hodi, M.D., Department of Medicine,
Harvard Medical School, Dana-Farber Cancer Institute. “This pooled analysis is
encouraging, particularly when considering that metastatic melanoma is one of
the most aggressive forms of cancer and historically, average survival was
just six to nine months.”

About The Analysis

This pooled analysis was conducted to provide a more precise estimate of the
long-term survival effect of Yervoy in patients with metastatic melanoma. It
is comprised of patient-level data from 12 prospective and retrospective
studies, including two Phase 3 trials (n=790), eight Phase 2 trials (n=821),
and two retrospective, observational studies (n=250), which have been or will
be reported on as individual studies. Three studies included overall survival
follow-up in some patients for up to ten years.

The analysis included both previously-treated (n=1,257) and previously
untreated patients (n=604) who received Yervoy at different doses and
regimens. The majority of patients received Yervoy 3 mg/kg (n=965) or 10 mg/kg
(n=706). Yervoy was given every 3 weeks for 4 doses, and most studies included
the option to receive either Yervoy retreatment or Yervoy maintenance therapy
for eligible patients.

About Yervoy

Yervoy, which is a recombinant, human monoclonal antibody, blocks the
cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative
regulator of T-cell activation. Yervoy binds to CTLA-4 and blocks the
interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been
shown to augment T-cell activation and proliferation. The mechanism of action
of Yervoy’s effect in patients with melanoma is indirect, possibly through
T-cell mediated anti-tumor immune responses. On March 25, 2011, the FDA
approved Yervoy 3 mg/kg monotherapy for patients with unresectable or
metastatic melanoma. Yervoy is now approved in more than 40 countries.

YERVOY^® (ipilimumab) INDICATION & IMPORTANT SAFETY INFORMATION

YERVOY (ipilimumab) is indicated for the treatment of unresectable or
metastatic melanoma.

Important Safety Information

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions due to
T-cell activation and proliferation. These immune-mediated reactions may
involve any organ system; however, the most common severe immune-mediated
adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these
immune-mediated reactions initially manifested during treatment; however, a
minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis,
neuropathy, and endocrinopathy and evaluate clinical chemistries including
liver function tests (LFTs) and thyroid function tests at baseline and before
each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid
therapy for severe immune-mediated reactions.

Recommended Dose Modifications

Withhold dose for any moderate immune-mediated adverse reactions or for
symptomatic endocrinopathy until return to baseline, improvement to mild
severity, or complete resolution, and patient is receiving <7.5 mg prednisone
or equivalent per day.

Permanently discontinue YERVOY for any of the following:

  *Persistent moderate adverse reactions or inability to reduce
    corticosteroid dose to 7.5 mg prednisone or equivalent per day
  *Failure to complete full treatment course within 16 weeks from
    administration of first dose
  *Severe or life-threatening adverse reactions, including any of the
    following:

       *Colitis with abdominal pain, fever, ileus, or peritoneal signs;
         increase in stool frequency (≥7 over baseline), stool incontinence,
         need for intravenous hydration for >24 hours, gastrointestinal
         hemorrhage, and gastrointestinal perforation
       *AST or ALT >5 × the upper limit of normal (ULN) or total bilirubin >3
         × the ULN
       *Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
         complicated by full-thickness dermal ulceration or necrotic, bullous,
         or hemorrhagic manifestations
       *Severe motor or sensory neuropathy, Guillain-Barré syndrome, or
         myasthenia gravis
       *Severe immune-mediated reactions involving any organ system
       *Immune-mediated ocular disease which is unresponsive to topical
         immunosuppressive therapy

Immune-mediated Enterocolitis:

  *In the pivotal Phase 3 study in YERVOY (ipilimumab)-treated patients,
    severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline,
    fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis
    occurred in 34 (7%) and moderate (diarrhea with up to 6 stools above
    baseline, abdominal pain, mucus or blood in stool; Grade 2) enterocolitis
    occurred in 28 (5%) patients
  *Across all YERVOY-treated patients (n=511), 5 (1%) developed intestinal
    perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were
    hospitalized for severe enterocolitis
  *Infliximab was administered to 5 of 62 (8%) patients with moderate,
    severe, or life-threatening immune-mediated enterocolitis following
    inadequate response to corticosteroids
  *Monitor patients for signs and symptoms of enterocolitis (such as
    diarrhea, abdominal pain, mucus or blood in stool, with or without fever)
    and of bowel perforation (such as peritoneal signs and ileus). In
    symptomatic patients, rule out infectious etiologies and consider
    endoscopic evaluation for persistent or severe symptoms
  *Permanently discontinue YERVOY in patients with severe enterocolitis and
    initiate systemic corticosteroids (1-2 mg/kg/day of prednisone or
    equivalent). Upon improvement to ≤Grade 1, initiate corticosteroid taper
    and continue over at least 1 month. In clinical trials, rapid
    corticosteroid tapering resulted in recurrence or worsening symptoms of
    enterocolitis in some patients
  *Withhold YERVOY (ipilimumab) for moderate enterocolitis; administer
    anti-diarrheal treatment and, if persistent for >1 week, initiate systemic
    corticosteroids (0.5 mg/kg/day prednisone or equivalent)

Immune-mediated Hepatitis:

  *In the pivotal Phase 3 study in YERVOY-treated patients, severe,
    life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the
    ULN or total bilirubin elevations >3x the ULN; Grade 3–5) occurred in 8
    (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in
    0.4%
  *13 (2.5%) additional YERVOY-treated patients experienced moderate
    hepatotoxicity manifested by LFT abnormalities (AST or ALT elevations
    >2.5x but ≤5x the ULN or total bilirubin elevation >1.5x but ≤3x the ULN;
    Grade 2)
  *Monitor LFTs (hepatic transaminase and bilirubin levels) and assess
    patients for signs and symptoms of hepatotoxicity before each dose of
    YERVOY. In patients with hepatotoxicity, rule out infectious or malignant
    causes and increase frequency of LFT monitoring until resolution
  *Permanently discontinue YERVOY in patients with Grade 3-5 hepatotoxicity
    and administer systemic corticosteroids (1-2 mg/kg/day of prednisone or
    equivalent). When LFTs show sustained improvement or return to baseline,
    initiate corticosteroid tapering and continue over 1 month. Across the
    clinical development program for YERVOY, mycophenolate treatment has been
    administered in patients with persistent severe hepatitis despite
    high-dose corticosteroids
  *Withhold YERVOY in patients with Grade 2 hepatotoxicity

Immune-mediated Dermatitis:

  *In the pivotal Phase 3 study in YERVOY-treated patients, severe,
    life-threatening, or fatal immune-mediated dermatitis (e.g.,
    Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated
    by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic
    manifestations; Grade 3–5) occurred in 13 (2.5%) patients

       *1 (0.2%) patient died as a result of toxic epidermal necrolysis
       *1 additional patient required hospitalization for severe dermatitis

  *There were 63 (12%) YERVOY-treated patients with moderate (Grade 2)
    dermatitis
  *Monitor patients for signs and symptoms of dermatitis such as rash and
    pruritus. Unless an alternate etiology has been identified, signs or
    symptoms of dermatitis should be considered immune-mediated
  *Permanently discontinue YERVOY (ipilimumab) in patients with severe,
    life-threatening, or fatal immune-mediated dermatitis (Grade 3-5).
    Administer systemic corticosteroids (1-2 mg/kg/day of prednisone or
    equivalent). When dermatitis is controlled, corticosteroid tapering should
    occur over a period of at least 1 month. Withhold YERVOY in patients with
    moderate to severe signs and symptoms
  *Treat mild to moderate dermatitis (e.g., localized rash and pruritus)
    symptomatically. Administer topical or systemic corticosteroids if there
    is no improvement within 1 week

Immune-mediated Neuropathies:

  *In the pivotal Phase 3 study in YERVOY-treated patients, 1 case of fatal
    Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor
    neuropathy were reported
  *Across the clinical development program of YERVOY, myasthenia gravis and
    additional cases of Guillain-Barré syndrome have been reported
  *Monitor for symptoms of motor or sensory neuropathy such as unilateral or
    bilateral weakness, sensory alterations, or paresthesia. Permanently
    discontinue YERVOY in patients with severe neuropathy (interfering with
    daily activities) such as Guillain-Barré–like syndromes
  *Institute medical intervention as appropriate for management of severe
    neuropathy. Consider initiation of systemic corticosteroids (1-2 mg/kg/day
    of prednisone or equivalent) for severe neuropathies. Withhold YERVOY in
    patients with moderate neuropathy (not interfering with daily activities)

Immune-mediated Endocrinopathies:

  *In the pivotal Phase 3 study in YERVOY- treated patients, severe to
    life-threatening immune-mediated endocrinopathies (requiring
    hospitalization, urgent medical intervention, or interfering with
    activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients

       *All 9patients had hypopituitarism, and some had additional
         concomitant endocrinopathies such as adrenal insufficiency,
         hypogonadism, and hypothyroidism
       *6 of the 9 patients were hospitalized for severe endocrinopathies

  *Moderate endocrinopathy (requiring hormone replacement or medical
    intervention; Grade 2) occurred in 12 (2.3%) YERVOY (ipilimumab)-treated
    patients and consisted of hypothyroidism, adrenal insufficiency,
    hypopituitarism, and 1 case each of hyperthyroidism and Cushing’s syndrome
  *Median time to onset of moderate to severe immune-mediated endocrinopathy
    was 11 weeks and ranged up to 19.3 weeks after the initiation of YERVOY
  *Monitor patients for clinical signs and symptoms of hypophysitis, adrenal
    insufficiency (including adrenal crisis), and hyper- or hypothyroidism

       *Patients may present with fatigue, headache, mental status changes,
         abdominal pain, unusual bowel habits, and hypotension, or nonspecific
         symptoms which may resemble other causes such as brain metastasis or
         underlying disease. Unless an alternate etiology has been identified,
         signs or symptoms should be considered immune-mediated
       *Monitor thyroid function tests and clinical chemistries at the start
         of treatment, before each dose, and as clinically indicated based on
         symptoms. In a limited number of patients, hypophysitis was diagnosed
         by imaging studies through enlargement of the pituitary gland

  *Withhold YERVOY in symptomatic patients. Initiate systemic corticosteroids
    (1-2 mg/kg/day of prednisone or equivalent) and initiate appropriate
    hormone replacement therapy. Long-term hormone replacement therapy may be
    necessary

Other Immune-mediated Adverse Reactions, Including Ocular Manifestations:

  *In the pivotal Phase 3 study in YERVOY-treated patients, clinically
    significant immune-mediated adverse reactions seen in <1% were: nephritis,
    pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic
    anemia
  *Across the clinical development program for YERVOY, likely immune-mediated
    adverse reactions also reported with <1% incidence were: myocarditis,
    angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica,
    conjunctivitis, blepharitis, episcleritis, scleritis, leukocytoclastic
    vasculitis, erythema multiforme, psoriasis, pancreatitis, arthritis,
    autoimmune thyroiditis, sarcoidosis, neurosensory hypoacusis, autoimmune
    central neuropathy (encephalitis), myositis, polymyositis, and ocular
    myositis
  *Permanently discontinue YERVOY (ipilimumab) for clinically significant or
    severe immune-mediated adverse reactions. Initiate systemic
    corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for severe
    immune-mediated adverse reactions
  *Administer corticosteroid eye drops for uveitis, iritis, or episcleritis.
    Permanently discontinue YERVOY for immune-mediated ocular disease
    unresponsive to local immunosuppressive therapy

Pregnancy & Nursing:

  *YERVOY is classified as pregnancy category C. There are no adequate and
    well-controlled studies of YERVOY in pregnant women. Use YERVOY during
    pregnancy only if the potential benefit justifies the potential risk to
    the fetus
  *Human IgG1 is known to cross the placental barrier and YERVOY is an IgG1;
    therefore, YERVOY has the potential to be transmitted from the mother to
    the developing fetus
  *It is not known whether YERVOY is secreted in human milk. Because many
    drugs are secreted in human milk and because of the potential for serious
    adverse reactions in nursing infants from YERVOY, a decision should be
    made whether to discontinue nursing or to discontinue YERVOY

Common Adverse Reactions:

  *The most common adverse reactions (≥5%) in patients who received YERVOY at
    3mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%),
    and colitis (8%)

Please see Full Prescribing Information, including Boxed WARNING regarding
immune-mediated adverse reactions available at www.bms.com.

YERVOY is a registered trademark of Bristol-Myers Squibb Company.

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 http://twitter.com/bmsnews.

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
research, development and commercialization of pharmaceutical 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. 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.

Contact:

Bristol-Myers Squibb
Media:
Melanie Brunner, 609-252-6338
melanie.brunner@bms.com
or
Sarah Koenig, 609-252-4145
sarah.koenig@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Ryan Asay, 609-252-5020
ryan.asay@bms.com
 
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