Bristol-Myers
Squibb Company (NYSE:BMY) today announced that the U.S. Food and
Drug Administration (FDA) has accepted for filing and review the
supplemental Biologics License Application (sBLA) for Opdivo (nivolumab)
for the treatment of previously untreated patients with unresectable
or metastatic melanoma. The FDA also granted Priority Review for this
application. The projected FDA action date is August 27, 2015.
Opdivo was first approved by the FDA in December 2014 for
patients with unresectable or metastatic melanoma and disease
progression following Yervoy (ipilimumab) and, if BRAF V600
mutation positive, a BRAF inhibitor. This initial indication was
approved under accelerated approval based on tumor response rate and
durability of response from CheckMate -037 clinical trial results. This
new sBLA accepted by the FDA includes data from CheckMate -066, which
evaluated Opdivo in treatment naïve patients with BRAF wild-type
advanced melanoma as compared to dacarbazine chemotherapy (DTIC). In the
trial, safety and tolerability were well-characterized with fewer
treatment-related Grade 3/4 adverse events observed with Opdivo
than dacarbazine.
“The CheckMate -066 trial marked the first time that a PD-1 immune
checkpoint inhibitor showed a survival benefit in a randomized Phase III
trial,” said Michael Giordano, senior vice president, Head of
Development, Oncology, Bristol-Myers Squibb. “We look forward to
continuing to work with the FDA to ensure cancer patients are provided
the latest clinical advances that have the potential for improved
responses and long-term survival.”
About Advanced Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled
growth of pigment-producing cells (melanocytes) located in the skin.
Metastatic melanoma is the deadliest form of the disease, and occurs
when cancer spreads beyond the surface of the skin to the other organs,
such as the lymph nodes, lungs, brain or other areas of the body. The
incidence of melanoma has been increasing for at least 30 years. In
2015, an estimated 73,870 melanoma cases will be diagnosed in the U.S.
Melanoma is mostly curable when treated in its early stages. However, in
its late stages, the average survival rate is just 6 months with a
1-year survival of 25.5%, making it one of the most aggressive forms of
cancer.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor
that has received approval from the U.S. FDA as a monotherapy in two
cancer indications. On March 5, 2015, Opdivo received FDA
approval for the treatment of patients with metastatic squamous
non-small cell lung cancer (NSCLC) with progression on or after
platinum-based chemotherapy.
In the U.S., Opdivo is also indicated for the treatment of
patients with unresectable or metastatic melanoma and disease
progression following Yervoy (ipilimumab) and, if BRAF V600
mutation positive, a BRAF inhibitor. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials. Opdivo became the first PD-1 immune checkpoint
inhibitor to receive regulatory approval anywhere in the world on July
4, 2014 when Ono Pharmaceutical Co. announced that it received
manufacturing and marketing approval in Japan for the treatment of
patients with unresectable melanoma.
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 7,000
patients have been enrolled worldwide.
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,
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 Pharmaceutical
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.
IMPORTANT SAFETY INFORMATION
Immune-Mediated Pneumonitis
-
Severe pneumonitis or interstitial lung disease, including fatal
cases, occurred with OPDIVO treatment. Across the clinical trial
experience in 691 patients with solid tumors, fatal immune-mediated
pneumonitis occurred in 0.7% (5/691) of patients receiving OPDIVO; no
cases occurred in Trial 1. In Trial 1, 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; one with Grade 3 and five with Grade 2. Monitor
patients for signs and symptoms of pneumonitis. Administer
corticosteroids for Grade 2 or greater pneumonitis. Permanently
discontinue OPDIVO for Grade 3 or 4 and withhold OPDIVO until
resolution for Grade 2.
Immune-Mediated Colitis
-
In Trial 1, 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; five with Grade 3 and one with Grade 2. Monitor patients for
immune-mediated colitis. Administer corticosteroids for Grade 2 (of
more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for Grade
2 or 3. Permanently discontinue OPDIVO for Grade 4 colitis or
recurrent colitis upon restarting OPDIVO.
Immune-Mediated Hepatitis
-
In Trial 1, 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; two with Grade 3 and one with
Grade 2. Monitor patients for abnormal liver tests prior to and
periodically during treatment. Administer corticosteroids for Grade 2
or greater transaminase elevations. Withhold OPDIVO for Grade 2 and
permanently discontinue OPDIVO for Grade 3 or 4 immune-mediated
hepatitis.
Immune-Mediated Nephritis and Renal Dysfunction
-
In Trial 1, 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. Monitor patients for
elevated serum creatinine prior to and periodically during treatment.
For Grade 2 or 3 serum creatinine elevation, withhold OPDIVO and
administer corticosteroids; if worsening or no improvement occurs,
permanently discontinue OPDIVO. Administer corticosteroids for Grade 4
serum creatinine elevation and permanently discontinue OPDIVO.
Immune-Mediated Hypothyroidism and Hyperthyroidism
-
In Trial 1, 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. Monitor thyroid function prior to and periodically
during treatment. Administer hormone replacement therapy for
hypothyroidism. Initiate medical management for control of
hyperthyroidism.
Other Immune-Mediated Adverse Reactions
-
The following clinically significant, immune-mediated adverse
reactions occurred in less than 2% of OPDIVO-treated patients: adrenal
insufficiency, uveitis, pancreatitis, facial and abducens nerve
paresis, demyelination, autoimmune neuropathy, motor dysfunction, and
vasculitis. Across clinical trials of OPDIVO administered at doses 3
mg/kg and 10 mg/kg, additional clinically significant, immune-mediated
adverse reactions were identified: hypophysitis, diabetic
ketoacidosis, hypopituitarism, Guillain-Barré syndrome, and myasthenic
syndrome. Based on the severity of adverse reaction, withhold OPDIVO,
administer high-dose corticosteroids, and, if appropriate, initiate
hormone- replacement therapy.
Embryofetal Toxicity
-
Based on its mechanism of action, OPDIVO 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 OPDIVO and for at
least 5 months after the last dose of OPDIVO.
Lactation
-
It is not known whether OPDIVO 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, advise women to discontinue breastfeeding during treatment.
Serious Adverse Reactions
-
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.
Common Adverse Reactions
-
The most common adverse reaction (≥20%) reported with OPDIVO was rash
(21%).
Please see US
Full Prescribing Information for OPDIVO.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical 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 this new indication or, if approved, that it
will become a commercially successful product. 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.
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