U.S. Food and Drug Administration Accepts for Priority Review the Supplemental Biologics License Application for Opdivo (nivolumab) in Patients with Advanced Renal Cell Carcinoma

Submission based on overall survival data from CheckMate -025, a
Phase 3 study comparing
Opdivo versus everolimus in this
patient population

Agency previously granted Opdivo Breakthrough
Therapy Designation for this indication

PRINCETON, N.J.–(BUSINESS WIRE)–Bristol-Myers
Squibb Company
(NYSE: BMY) today announced that the U.S. Food
and Drug Administration (FDA) has accepted for filing and priority
review a supplemental Biologics License Application (sBLA) for Opdivo for
the treatment of patients with advanced renal cell carcinoma (RCC) who
have received prior anti-angiogenic therapy. The FDA previously granted Opdivo
Breakthrough Therapy Designation for this indication, underscoring the
critical need for new treatment options for patients with advanced RCC
who have received prior therapy. The projected FDA action date is March
16, 2016.

Michael Giordano, M.D., senior vice president, head of Oncology
Development, Bristol-Myers Squibb, commented, “There remains a
significant unmet medical need for advanced renal cell carcinoma
patients who have received prior therapy and are often repeatedly
treated with agents that are similar in mechanism. We are pleased the
FDA has accepted our sBLA for Opdivo in RCC, and we will continue
to work with urgency to bring Opdivo to patients with this
cancer.”

This sBLA submission is based on CheckMate -025, a Phase 3 study that
evaluated the overall survival of Opdivo in patients with
previously treated advanced RCC versus everolimus, a current standard of
care in this patient population. The trial was stopped early in July
2015 because an assessment conducted by the independent Data Monitoring
Committee (DMC) concluded that the study met its primary endpoint of
overall survival. Data from CheckMate -025 were recently presented at
the 2015 European Cancer Congress and simultaneously published in The
New England Journal of Medicine.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer in
adults, accounting for more than 100,000 deaths worldwide each year.
Clear-cell RCC is the most prevalent type of RCC and constitutes 80% to
90% of all cases. RCC is approximately twice as common in men as in
women, with the highest rates of the disease found in North America and
Europe. Globally, the five-year survival rate for those diagnosed with
metastatic, or advanced, kidney cancer is 12.1%.

About Opdivo

Bristol-Myers Squibb has a broad, global development program to study Opdivo
in multiple tumor types consisting of more than 50 trials – as
monotherapy or in combination with other therapies – in which more than
8,000 patients have been enrolled worldwide. Opdivo is the first
PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere
in the world in July 2014, and currently has regulatory approval in more
than 37 countries including the United States, Japan, and in the
European Union.

Indications and Important Safety Information for OPDIVO® (nivolumab)

INDICATIONS

OPDIVO® (nivolumab) is indicated for the treatment of unresectable or
metastatic melanoma as a single agent in patients with disease
progression following ipilimumab and, if BRAF V600 mutation positive, a
BRAF inhibitor and in combination with ipilimumab in patients with BRAF
V600 wild-type melanoma.

These indications are approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for these
indications may be contingent upon verification and description of
clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with metastatic non-small cell lung cancer (NSCLC) with
progression on or after platinum-based chemotherapy. Patients with EGFR
or ALK genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving OPDIVO.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse
reactions. 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), adrenocorticotropic hormone
(ACTH) level, 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.

Immune-Mediated Pneumonitis

Immune-mediated pneumonitis or interstitial lung disease, including
fatal cases, occurred with OPDIVO treatment. Across the clinical trial
experience with solid tumors, fatal immune-mediated pneumonitis occurred
in 0.5% (5/978) of patients receiving OPDIVO as a single agent. Monitor
patients for signs with radiographic imaging and symptoms of
pneumonitis. Administer corticosteroids for Grade 2 or greater
pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until
resolution for Grade 2. In Checkmate 037, pneumonitis, including
interstitial lung disease, occurred in 3.4% (9/268) of patients
receiving OPDIVO and none of the 102 patients receiving chemotherapy.
Immune-mediated pneumonitis occurred in 2.2% (6/268) of patients
receiving OPDIVO; Grade 3 (n=1) and Grade 2 (n=5).

In Checkmate 057, immune-mediated pneumonitis, including interstitial
lung disease, occurred in 3.4% (10/287) of patients receiving OPDIVO as
a single agent: Grade 3 (n=5), Grade 2 (n=2), and Grade 1 (n=3). Across
the clinical trial experience in 188 patients with melanoma who received
OPDIVO in combination with YERVOY, in Checkmate 069 (n=94) and an
additional dose-finding study (n=94), fatal immune-mediated pneumonitis
occurred in 0.5% (1/188) of patients. In Checkmate 069, there were six
additional patients who died without resolution of abnormal respiratory
findings. In Checkmate 069, pneumonitis, including interstitial lung
disease, occurred in 10% (9/94) of patients receiving OPDIVO in
combination with YERVOY and 2.2% (1/46) of patients receiving YERVOY.
Immune-mediated pneumonitis occurred in 6% (6/94) of patients receiving
OPDIVO in combination with YERVOY: Grade 5 (n=1), Grade 3 (n=2) and
Grade 2 (n=3).

Immune-Mediated Colitis

Immune-mediated colitis can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of colitis. Administer corticosteroids
for Grade 2 (of more than 5 days duration), 3, or 4 colitis. As a single
agent, withhold OPDIVO for Grade 2 or 3 and permanently discontinue for
Grade 4 or recurrent colitis upon restarting OPDIVO. In combination with
YERVOY, withhold OPDIVO for Grade 2 and permanently discontinue for
Grade 3 or 4 or recurrent colitis upon restarting OPDIVO. In Checkmate
037, diarrhea or colitis occurred in 21% (57/268) of patients receiving
OPDIVO and 18% (18/102) of patients receiving chemotherapy.
Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving
OPDIVO; Grade 3 (n=5) and Grade 2 (n=1). In Checkmate 057, diarrhea or
colitis occurred in 17% (50/287) of patients receiving OPDIVO as a
single agent. Immune-mediated colitis occurred in 2.4% (7/287) of
patients: Grade 3 (n=3), Grade 2 (n=2), and Grade 1 (n=2). In Checkmate
069, diarrhea or colitis occurred in 57% (54/94) of patients receiving
OPDIVO in combination with YERVOY and 46% (21/46) of patients receiving
YERVOY. Immune-mediated colitis occurred in 33% (31/94) of patients
receiving OPDIVO in combination with YERVOY: Grade 4 (n=1), Grade 3
(n=16), Grade 2 (n=9), and Grade 1 (n=5).

In a separate Phase 3 study of YERVOY 3 mg/kg, 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%)
patients. Across all YERVOY-treated patients in that study (n=511), 5
(1%) developed intestinal perforation, 4 (0.8%) died as a result of
complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

Immune-mediated hepatitis can occur with OPDIVO treatment. Monitor
patients for abnormal liver tests prior to and periodically during
treatment. Administer corticosteroids for Grade 2 or greater
transaminase elevations. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 immune-mediated hepatitis. In Checkmate
037, there was an increased incidence of liver test abnormalities in the
OPDIVO-treated group as compared to the chemotherapy-treated group, with
increases in AST (28% vs 12%), alkaline phosphatase (22% vs 13%), ALT
(16% vs 5%), and total bilirubin (9% vs 0). Immune-mediated hepatitis
occurred in 1.1% (3/268) of patients receiving OPDIVO; Grade 3 (n=2) and
Grade 2 (n=1). In Checkmate 057, one patient (0.3%) developed
immune-mediated hepatitis. In Checkmate 069, immune-mediated hepatitis
occurred in 15% (14/94) of patients receiving OPDIVO in combination with
YERVOY: Grade 4 (n=3), Grade 3 (n=9), and Grade 2 (n=2).

In a separate Phase 3 study of YERVOY 3 mg/kg, 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%.

Immune-Mediated Dermatitis

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening,
or fatal immune-mediated dermatitis (eg, 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.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor
neuropathy were reported.

Immune-Mediated Endocrinopathies

Hypophysitis, adrenal insufficiency, and thyroid disorders can occur
with OPDIVO treatment. Monitor patients for signs and symptoms of
hypophysitis, signs and symptoms of adrenal insufficiency during and
after treatment, and thyroid function prior to and periodically during
treatment. Administer corticosteroids for Grade 2 or greater
hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for
Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4
adrenal insufficiency. Withhold for Grade 2 and permanently discontinue
for Grade 3 or 4 adrenal insufficiency. Administer hormone replacement
therapy for hypothyroidism. Initiate medical management for control of
hyperthyroidism.

In Checkmate 069, hypophysitis occurred in 13% (12/94) of patients
receiving OPDIVO in combination with YERVOY: Grade 3 (n=2) and Grade 2
(n=10). Adrenal insufficiency occurred in 1% (n=555) of patients
receiving OPDIVO as a single agent. In Checkmate 069, adrenal
insufficiency occurred in 9% (8/94) of patients receiving OPDIVO in
combination with YERVOY: Grade 3 (n=3), Grade 2 (n=4), and Grade 1
(n=1). In Checkmate 069, hypothyroidism occurred in 19% (18/94) of
patients receiving OPDIVO in combination with YERVOY. All were Grade 1
or 2 in severity except for one patient who experienced Grade 3
autoimmune thyroiditis. Grade 1 hyperthyroidism occurred in 2.1% (2/94)
of patients receiving OPDIVO in combination with YERVOY. In Checkmate
037, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of patients
receiving OPDIVO and none of the 102 patients receiving chemotherapy.
Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of patients
receiving OPDIVO and 1% (1/102) of patients receiving chemotherapy. In
Checkmate 057, Grade 1 or 2 hypothyroidism, including thyroiditis,
occurred in 7% (20/287) and elevated TSH occurred in 17% of patients
receiving OPDIVO as a single agent. Grade 1 or 2 hyperthyroidism
occurred in 1.4% (4/287) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, 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 9 patients 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.

Immune-Mediated Nephritis and Renal Dysfunction

Immune-mediated nephritis can occur with OPDIVO treatment. Monitor
patients for elevated serum creatinine prior to and periodically during
treatment. For Grade 2 or 3 increased serum creatinine, withhold and
administer corticosteroids; if worsening or no improvement occurs,
permanently discontinue. Administer corticosteroids for Grade 4 serum
creatinine elevation and permanently discontinue. In Checkmate 037,
there was an increased incidence of elevated creatinine in the
OPDIVO-treated group as compared to the chemotherapy-treated group (13%
vs 9%). Grade 2 or 3 immune-mediated nephritis or renal dysfunction
occurred in 0.7% (2/268) of patients. In Checkmate 057, Grade 2
immune-mediated renal dysfunction occurred in 0.3% (1/287) of patients
receiving OPDIVO as a single agent. In Checkmate 069, Grade 2 or higher
immune-mediated nephritis or renal dysfunction occurred in 2.1% (2/94)
of patients. One patient died without resolution of renal dysfunction.

Immune-Mediated Rash

Immune-mediated rash can occur with OPDIVO treatment. Monitor patients
for rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold for
Grade 3 and permanently discontinue for Grade 4. In Checkmate 037
(n=268), the incidence of rash was 21%; the incidence of Grade 3 or 4
rash was 0.4%. In Checkmate 057, immune-mediated rash occurred in 6%
(17/287) of patients receiving OPDIVO as a single agent including four
Grade 3 cases. In Checkmate 069, immune-mediated rash occurred in 37%
(35/94) of patients receiving OPDIVO in combination with YERVOY: Grade 3
(n=6), Grade 2 (n=10), and Grade 1 (n=19).

Immune-Mediated Encephalitis

Immune-mediated encephalitis can occur with OPDIVO treatment. Withhold
OPDIVO in patients with new-onset moderate to severe neurologic signs or
symptoms and evaluate to rule out other causes. If other etiologies are
ruled out, administer corticosteroids and permanently discontinue OPDIVO
for immune-mediated encephalitis. Across clinical trials of 8490
patients receiving OPDIVO as a single agent or in combination with
YERVOY, <1% of patients were identified as having encephalitis. In
Checkmate 057, fatal limbic encephalitis occurred in one patient (0.3%)
receiving OPDIVO as a single agent.

Other Immune-Mediated Adverse Reactions

Based on the severity of adverse reaction, permanently discontinue or
withhold treatment, administer high-dose corticosteroids, and, if
appropriate, initiate hormone-replacement therapy. The following
clinically significant immune-mediated adverse reactions occurred in <2%
(n=555) of single-agent OPDIVO-treated patients: uveitis, pancreatitis,
abducens nerve paresis, demyelination, polymyalgia rheumatica, and
autoimmune neuropathy. Across clinical trials of OPDIVO administered as
a single agent at doses 3 mg/kg and 10 mg/kg, additional clinically
significant, immune-mediated adverse reactions were identified: facial
nerve paralysis, motor dysfunction, vasculitis, diabetic ketoacidosis,
and myasthenic syndrome. In Checkmate 069, the following additional
immune-mediated adverse reactions occurred in 1% of patients treated
with OPDIVO in combination with YERVOY: Guillain-Barré syndrome and
hypopituitarism. Across clinical trials of OPDIVO in combination with
YERVOY, the following additional clinically significant, immune-mediated
adverse reactions were identified: uveitis, sarcoidosis, duodenitis,
pancreatitis, and gastritis.

Infusion Reactions

Severe infusion reactions have been reported in <1% of patients in
clinical trials of OPDIVO as a single agent. In Checkmate 057, Grade 2
infusion reactions occurred in 1% (3/287) of patients receiving OPDIVO
as a single agent. In Checkmate 069, Grade 2 infusion reactions occurred
in 3% (3/94) of patients receiving OPDIVO in combination with YERVOY.
Discontinue OPDIVO in patients with severe or life-threatening infusion
reactions. Interrupt or slow the rate of infusion in patients with mild
or moderate infusion reactions.

Embryofetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal
harm when administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential to
use effective contraception during treatment with an OPDIVO- or
YERVOY-containing regimen and for at least 5 months after the last dose
of OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk.
Because many drugs, including antibodies, are excreted in human milk and
because of the potential for serious adverse reactions in nursing
infants from OPDIVO-containing regimen, advise women to discontinue
breastfeeding during treatment. Advise women to discontinue nursing
during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients
receiving OPDIVO. Grade 3 and 4 adverse reactions occurred in 42% of
patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug
reactions reported in 2% to <5% of patients receiving OPDIVO were
abdominal pain, hyponatremia, increased aspartate aminotransferase, and
increased lipase. In Checkmate 057, serious adverse reactions occurred
in 47% of patients receiving OPDIVO as a single agent. The most frequent
serious adverse reactions reported in ≥2% of patients were pneumonia,
pulmonary embolism, dyspnea, pleural effusion, and respiratory failure.
In Checkmate 069, serious adverse reactions occurred in 62% of patients
receiving OPDIVO; the most frequent serious adverse events with OPDIVO
in combination with YERVOY, as compared to YERVOY alone, were colitis
(17% vs 9%), diarrhea (9% vs 7%), pyrexia (6% vs 7%), and pneumonitis
(5% vs 0).

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with
OPDIVO was rash (21%). In Checkmate 057, the most common adverse
reactions (≥20%) reported with OPDIVO as a single agent were fatigue
(49%), musculoskeletal pain (36%), cough (30%), decreased appetite
(29%), and constipation (23%). In Checkmate 069, the most common adverse
reactions (≥20%) reported in patients receiving OPDIVO in combination
with YERVOY vs YERVOY alone were rash (67% vs 57%), pruritus (37% vs
26%), headache (24% vs 20%), vomiting (23% vs 15%), and colitis (22% vs
11%).

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse
reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue
(41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Please
see U.S. Full Prescribing Information, including Boxed WARNING regarding
immune-mediated adverse reactions, for YERVOY.

Please
see U.S. Full Prescribing Information for OPDIVO
.

Immuno-Oncology at Bristol-Myers Squibb

Surgery, radiation, cytotoxic or targeted therapies have represented the
mainstay of cancer treatment over the last several decades, but
long-term survival and a positive quality of life have remained elusive
for many patients with advanced disease.

To address this unmet medical need, Bristol-Myers Squibb is leading
research in an innovative field of cancer research and treatment known
as Immuno-Oncology, which involves agents whose primary mechanism is to
work directly with the body’s immune system to fight cancer. The company
is exploring a variety of compounds and immunotherapeutic approaches for
patients with different types of cancer, including researching the
potential of combining Immuno-Oncology agents that target different
pathways in the treatment of cancer.

Bristol-Myers Squibb is committed to advancing the science of
Immuno-Oncology, with the goal of changing survival expectations and the
way patients live with cancer.

About the Bristol-Myers Squibb and Ono
Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co.,
Bristol-Myers Squibb expanded its territorial rights to develop and
commercialize Opdivo globally, except in Japan, South Korea
and Taiwan, where Ono had retained all rights to the compound at the
time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded
the companies’ strategic collaboration agreement to jointly develop and
commercialize multiple immunotherapies – as single agents and
combination regimens – for patients with cancer in Japan, South Korea
and Taiwan.

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.
Among other risks, there can be no guarantee that Opdivo will receive
regulatory approval for the additional indication described in this
release. 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, 2014 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.

Contacts

Bristol-Myers Squibb
Media:
Carrie Fernandez,
609-419-5448, cell: 215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya
Dajani, 609-252-5330, cell: 215-666-1515
ranya.dajani@bms.com
or
Bill
Szablewski, 609-252-5894, cell: 215-801-0906
william.szablewski@bms.com