Award recognizes Bristol-Myers Squibb for driving innovation in immuno-oncology
Bristol-Myers Squibb’s Immuno-Oncology franchise is three-time winner of Prix Galien USA awards
Bristol-Myers
Squibb Company (NYSE:BMY) announced today that it received the Prix
Galien USA Discovery of the Decade biotech award for Yervoy
(ipilimumab), the Company’s recombinant, human monoclonal antibody. In
honor of the 10th anniversary of the Prix Galien awards and
recognizing this decade as one of history's most productive for
research, this special honor distinguishes Bristol-Myers Squibb for its
innovative discovery and development of Yervoy, which is now
approved in more than 50 countries for treatment of unresectable or
metastatic melanoma. The award is also a testament to Bristol-Myers
Squibb’s efforts to establish Immuno-Oncology as a transformational
approach to treating a wide range of malignancies.
“We are honored to receive this special recognition for Yervoy,
an agent that ushered in what can easily be described as a historical
time in cancer research,” said Francis
Cuss, MB, BChir, FRCP, chief scientific officer and executive vice
president, Research & Development, Bristol-Myers Squibb. “We are
extremely proud that the highly distinguished selection committee
recognized the extraordinary vision of our scientists and the strength
of our research and development program, which includes a robust
portfolio of early assets both in Immuno-Oncology and in targeted
therapies.”
The announcement was made during the tenth annual Prix Galien USA Awards
Ceremony held on October 27, 2016 in New York City. The Prix Galien
Discovery of the Decade award, which is selected by a preeminent
scientific committee that includes several Nobel Laureates, honors
outstanding achievements in improving the human condition through the
development of innovative therapies. This is the third Prix Galien honor
received by Bristol-Myers Squibb, the only company to receive the Prix
Galien USA Best Biotechnology Product award for two Immuno-Oncology
agents. In 2012, Yervoy (ipilimumab) received the Best
Biotechnology Product award, following its initial approval for
unresectable or metastatic melanoma. In 2015, Opdivo was named
Best Biotechnology Product, following its accelerated approval for
unresectable or metastatic melanoma and disease progression following
treatment with Yervoy and (if BRAF V600 mutation-positive)
a BRAF inhibitor. Building on this pioneering science, the
Company continues to research the potential of Immuno-Oncology to extend
survival in some of the hardest-to-treat cancers.
Bristol-Myers Squibb: At the Forefront of
Immuno-Oncology Science & Innovation
At Bristol-Myers Squibb, patients are at the center of everything we do.
Our vision for the future of cancer care is focused on researching and
developing transformational Immuno-Oncology (I-O) medicines that will
raise survival expectations in hard-to-treat cancers and will change the
way patients live with cancer.
We are leading the scientific understanding of I-O through our extensive
portfolio of investigational and approved agents, including the first
combination of two I-O agents in metastatic melanoma, and our
differentiated clinical development program, which is studying broad
patient populations across more than 20 types of cancers with 11
clinical-stage molecules designed to target different immune system
pathways. Our deep expertise and innovative clinical trial designs
uniquely position us to advance the science of combinations across
multiple tumors and potentially deliver the next wave of I-O combination
regimens with a sense of urgency. We also continue to pioneer research
that will help facilitate a deeper understanding of the role of immune
biomarkers and inform which patients will benefit most from I-O
therapies.
We understand making the promise of I-O a reality for the many patients
who may benefit from these therapies requires not only innovation on our
part but also close collaboration with leading experts in the field. Our
partnerships with academia, government, advocacy and biotech companies
support our collective goal of providing new treatment options to
advance the standards of clinical practice.
About Yervoy
Yervoy is a recombinant, human monoclonal antibody that binds to
the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a
negative regulator of T-cell activity. 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, including the activation and proliferation of tumor
infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also
reduce T-regulatory cell function, which may contribute to a general
increase in T-cell responsiveness, including the anti-tumor immune
response. On March 25, 2011, the U.S. Food and Drug Administration (FDA)
approved Yervoy 3 mg/kg monotherapy for patients with
unresectable or metastatic melanoma. Yervoy is approved for
unresectable or metastatic melanoma in more than 50 countries. There is
a broad, ongoing development program in place for Yervoy spanning
multiple tumor types.
Indications and Important Safety Information for YERVOY
®
(ipilimumab)
Indications
YERVOY® (ipilimumab) is indicated for the treatment of
unresectable or metastatic melanoma.
YERVOY® (ipilimumab) is indicated for the adjuvant treatment
of patients with cutaneous melanoma with pathologic involvement of
regional lymph nodes of more than 1 mm who have undergone complete
resection, including total lymphadenectomy.
Important Safety Information
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY (ipilimumab) 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.
Permanently discontinue YERVOY and initiate systemic high-dose
corticosteroid therapy for severe immune-mediated reactions.
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.
Recommended Dose Modifications
Endocrine: Withhold YERVOY for systemic endocrinopathy. Resume YERVOY in
patients with complete or partial resolution of adverse reactions (Grade
0-1) and who are receiving <7.5 mg prednisone or equivalent per day.
Permanently discontinue YERVOY for symptomatic reactions lasting 6 weeks
or longer or an inability to reduce corticosteroid dose to 7.5 mg
prednisone or equivalent per day.
Ophthalmologic: Permanently discontinue YERVOY for Grade 2-4 reactions
not improving to Grade 1 within 2 weeks while receiving topical therapy
or requiring systemic treatment.
All Other Organ Systems: Withhold YERVOY for Grade 2 adverse reactions.
Resume YERVOY in patients with complete or partial resolution of adverse
reactions (Grade 0-1) and who are receiving <7.5 mg prednisone or
equivalent per day. Permanently discontinue YERVOY for Grade 2 reactions
lasting 6 weeks or longer, an inability to reduce corticosteroid dose to
7.5 mg prednisone or equivalent per day, and Grade 3 or 4 adverse
reactions.
Immune-mediated Enterocolitis:
Immune-mediated enterocolitis, including fatal cases, can occur with
YERVOY. 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. Withhold YERVOY
for moderate enterocolitis; administer anti-diarrheal treatment and, if
persistent for >1 week, initiate systemic corticosteroids (0.5 mg/kg/day
prednisone or equivalent). 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. Consider adding
anti-TNF or other immunosuppressant agents for management of
immune-mediated enterocolitis unresponsive to systemic corticosteroids
within 3-5 days or recurring after symptom improvement. In patients
receiving YERVOY 3 mg/kg in Trial 1, severe, life-threatening, or fatal
(diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs;
Grade 3-5) immune-mediated enterocolitis occurred in 34 YERVOY-treated
patients (7%) and moderate (diarrhea with up to 6 stools above baseline,
abdominal pain, mucus or blood in stool; Grade 2) enterocolitis occurred
in 28 YERVOY-treated patients (5%). 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 (8%) of the 62 patients
with moderate, severe, or life-threatening immune-mediated enterocolitis
following inadequate response to corticosteroids. In patients receiving
YERVOY 10 mg/kg in Trial 2, Grade 3-5 immune-mediated enterocolitis
occurred in 76 patients (16%) and Grade 2 enterocolitis occurred in 68
patients (14%). Seven (1.5%) developed intestinal perforation and 3
patients (0.6%) died as a result of complications.
Immune-mediated Hepatitis:
Immune-mediated hepatitis, including fatal cases, can occur with YERVOY.
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. Withhold YERVOY in patients with Grade 2 hepatotoxicity.
Permanently discontinue YERVOY in patients with Grade 3-4 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. In patients receiving YERVOY 3 mg/kg in Trial
1, severe, life-threatening, or fatal hepatotoxicity (AST or ALT
elevations >5× the ULN or total bilirubin elevations >3× the ULN; Grade
3-5) occurred in 8 YERVOY-treated patients (2%), with fatal hepatic
failure in 0.2% and hospitalization in 0.4%. An additional 13 patients
(2.5%) experienced moderate hepatotoxicity manifested by LFT
abnormalities (AST or ALT elevations >2.5× but ≤5× the ULN or total
bilirubin elevation >1.5× but ≤3× the ULN; Grade 2). In a dose-finding
trial, Grade 3 increases in transaminases with or without concomitant
increases in total bilirubin occurred in 6 of 10 patients who received
concurrent YERVOY (3 mg/kg) and vemurafenib (960 mg BID or 720 mg BID).
In patients receiving YERVOY 10 mg/kg in Trial 2, Grade 3-4
immune-mediated hepatitis occurred in 51 patients (11%) and moderate
Grade 2 immune-mediated hepatitis occurred in 22 patients (5%). Liver
biopsy performed in 6 patients with Grade 3-4 hepatitis showed evidence
of toxic or autoimmune hepatitis.
Immune-mediated Dermatitis:
Immune-mediated dermatitis, including fatal cases, can occur with
YERVOY. 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.
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. Withhold YERVOY in patients with
moderate to severe signs and symptoms. Permanently discontinue YERVOY 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.
In patients receiving YERVOY 3 mg/kg in Trial 1, 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 YERVOY-treated
patients (2.5%); 1 patient (0.2%) died as a result of toxic epidermal
necrolysis and 1 additional patient required hospitalization for severe
dermatitis. There were 63 patients (12%) with moderate (Grade 2)
dermatitis. In patients receiving YERVOY 10 mg/kg in Trial 2, Grade 3-4
immune-mediated dermatitis occurred in 19 patients (4%). There were 99
patients (21%) with moderate Grade 2 dermatitis.
Immune-mediated Neuropathies:
Immune-mediated neuropathies, including fatal cases, can occur with
YERVOY. Monitor for symptoms of motor or sensory neuropathy such as
unilateral or bilateral weakness, sensory alterations, or paresthesia.
Withhold YERVOY in patients with moderate neuropathy (not interfering
with daily activities). Permanently discontinue YERVOY in patients with
severe neuropathy (interfering with daily activities), such as
Guillain-Barre-like syndromes. Institute medical intervention as
appropriate for management for severe neuropathy. Consider initiation of
systemic corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for
severe neuropathies. In patients receiving YERVOY 3 mg/kg in Trial 1, 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. In patients receiving YERVOY
10 mg/kg in Trial 2, Grade 3-5 immune-mediated neuropathy occurred in 8
patients (2%); the sole fatality was due to complications of
Guillain-Barré syndrome. Moderate Grade 2 immune-mediated neuropathy
occurred in 1 patient (0.2%).
Immune-mediated Endocrinopathies:
Immune-mediated endocrinopathies, including life-threatening cases, can
occur with 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 clinical chemistries, adrenocorticotropic
hormone (ACTH) level, and thyroid function tests 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 and consider referral to an
endocrinologist. Initiate systemic corticosteroids (1-2 mg/kg/day of
prednisone or equivalent) and initiate appropriate hormone replacement
therapy. In patients receiving YERVOY 3 mg/kg in Trial 1, 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 YERVOY-treated
patients (1.8%). All 9 patients had hypopituitarism, and some had
additional concomitant endocrinopathies such as adrenal insufficiency,
hypogonadism, and hypothyroidism. Six of the 9 patients were
hospitalized for severe endocrinopathies. Moderate endocrinopathy
(requiring hormone replacement or medical intervention; Grade 2)
occurred in 12 patients (2.3%) and consisted of hypothyroidism, adrenal
insufficiency, hypopituitarism, and 1 case each of hyperthyroidism and
Cushing's syndrome. The median time to onset of moderate to severe
immune-mediated endocrinopathy was 2.5 months and ranged up to 4.4
months after the initiation of YERVOY. In patients receiving YERVOY 10
mg/kg in Trial 2, Grade 3-4 immune-mediated endocrinopathies occurred in
39 patients (8%) and Grade 2 immune-mediated endocrinopathies occurred
in 93 patients (20%). Of the 39 patients with Grade 3-4 immune-mediated
endocrinopathies, 35 patients had hypopituitarism (associated with 1 or
more secondary endocrinopathies, e.g., adrenal insufficiency,
hypogonadism, and hypothyroidism), 3 patients had hyperthyroidism, and 1
had primary hypothyroidism. The median time to onset of Grade 3-4
immune-mediated endocrinopathy was 2.2 months (range: 2 days-8 months).
Twenty-seven (69.2%) of the 39 patients were hospitalized for
immune-mediated endocrinopathies. Of the 93 patients with Grade 2
immune-mediated endocrinopathy, 74 had primary hypopituitarism
(associated with 1 or more secondary endocrinopathy, e.g., adrenal
insufficiency, hypogonadism, and hypothyroidism), 9 had primary
hypothyroidism, 3 had hyperthyroidism, 3 had thyroiditis with hypo- or
hyperthyroidism, 2 had hypogonadism, 1 had both hyperthyroidism and
hypopituitarism, and 1 subject developed Graves’ ophthalmopathy. The
median time to onset of Grade 2 immune-mediated endocrinopathy was 2.1
months (range: 9 days-19.3 months).
Other Immune-mediated Adverse Reactions, Including Ocular
Manifestations:
Permanently discontinue YERVOY 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. In Trial 1, the following clinically significant
immune-mediated adverse reactions were seen in <1% of YERVOY-treated
patients: nephritis, pneumonitis, meningitis, pericarditis, uveitis,
iritis, and hemolytic anemia. In Trial 2, the following clinically
significant immune-mediated adverse reactions were seen in <1% of
YERVOY-treated patients unless specified: eosinophilia (2.1%),
pancreatitis (1.3%), meningitis, pneumonitis, sarcoidosis, pericarditis,
uveitis and fatal myocarditis. Across 21 dose-ranging trials
administering YERVOY at doses of 0.1 to 20 mg/kg (n=2478), the following
likely immune-mediated adverse reactions were also reported with <1%
incidence: angiopathy, temporal arteritis, vasculitis, polymyalgia
rheumatica, conjunctivitis, blepharitis, episcleritis, scleritis,
iritis, leukocytoclastic vasculitis, erythema multiforme, psoriasis,
arthritis, autoimmune thyroiditis, neurosensory hypoacusis, autoimmune
central neuropathy (encephalitis), myositis, polymyositis, ocular
myositis, hemolytic anemia, and nephritis.
Embyro-fetal Toxicity
Based on its mechanism of action, YERVOY can cause fetal harm when
administered to a pregnant woman. The effects of YERVOY are likely to be
greater during the second and third trimesters of pregnancy. Advise
pregnant women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during treatment
with a YERVOY-containing regimen and for 3 months after the last dose of
YERVOY.
Lactation
It is not known whether YERVOY is secreted in human milk. Advise women
to discontinue nursing during treatment with YERVOY and for 3 months
following the final dose.
Common Adverse Reactions:
The most common adverse reactions (≥5%) in patients who received YERVOY
at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritis (31%), rash
(29%), and colitis (8%). The most common adverse reactions (≥5%) in
patients who received YERVOY at 10 mg/kg were rash (50%), diarrhea
(49%), fatigue (46%), pruritus (45%), headache (33%), weight loss (32%),
nausea (25%), pyrexia (18%), colitis (16%), decreased appetite (14%),
vomiting (13%), and insomnia (10%).
Please see U.S.
Full Prescribing Information, including Boxed WARNING
regarding immune-mediated adverse reactions.
About the Bristol-Myers Squibb and Ono
Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co.,
Ltd (Ono) 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 us at BMS.com or
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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, 2015 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.
References
1. Opdivo Prescribing Information. Opdivo U.S. Product Information. Last
updated: September 2016. Princeton, NJ: Bristol-Myers Squibb Company.