PRINCETON, N.J.--(BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE:BMY) today announced that the U.S. Food and
Drug Administration (FDA) has extended the action date for the
supplemental Biologics License Application (sBLA) for Opdivo for
the treatment of patients with previously untreated advanced melanoma.
The company has taken the opportunity to submit additional data from the Opdivo
clinical trial program to ensure the broadest data set, irrespective of
BRAF status, was available for review. This submission constitutes a
major amendment that will require additional time for review and the new
FDA action date is November 27, 2015.
The sBLA was accepted by the FDA for filing and received priority review
designation on April 29, 2015, and included data from the Phase 3
CheckMate -066 trial which evaluated Opdivo in treatment naïve
patients with BRAF wild-type advanced melanoma as compared to
dacarbazine chemotherapy (DTIC). The company will continue to work
closely with the agency to support the review of this sBLA for Opdivo.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor
that has received approval from the FDA as a monotherapy in two cancer
indications. On March 4, 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 8,000 patients
have been enrolled worldwide.
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 or Trial 3. 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. In
Trial 3, immune-mediated pneumonitis occurred in 6% (7/117) of
patients receiving OPDIVO, including, five Grade 3 and two Grade 2
cases. 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. In Trial 3, diarrhea
occurred in 21% (24/117) of patients receiving OPDIVO. Grade 3
immune-mediated colitis occurred in 0.9% (1/117) of patients. 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. In Trial 3, the incidences of increased liver test values
were AST (16%), alkaline phosphatase (14%), ALT (12%), and total
bilirubin (2.7%). 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. In Trial 3, the
incidence of elevated creatinine was 22%. Immune-mediated renal
dysfunction (Grade 2) occurred in 0.9% (1/117) 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. In Trial 3, hypothyroidism occurred in 4.3% (5/117) of
patients receiving OPDIVO. Hyperthyroidism occurred in 1.7% (2/117) of
patients, including one Grade 2 case. 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
-
In Trial 1 and 3 (n=385), the following clinically significant
immune-mediated adverse reactions occurred in <2% of OPDIVO-treated
patients: adrenal insufficiency, uveitis, pancreatitis, facial and
abducens nerve paresis, demyeliniation, 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
-
In Trial 1, 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 Trial 3, serious adverse reactions occurred in 59% of patients
receiving OPDIVO. The most frequent serious adverse drug reactions
reported in =2% of patients were dyspnea, pneumonia, chronic
obstructive pulmonary disease exacerbation, pneumonitis,
hypercalcemia, pleural effusion, hemoptysis, and pain.
Common Adverse Reactions
-
The most common adverse reactions (=20%) reported with OPDIVO in Trial
1 were rash (21%) and in Trial 3 were fatigue (50%), dyspnea (38%),
musculoskeletal pain (36%), decreased appetite (35%), cough (32%),
nausea (29%), and constipation (24%).
Please see U.S. Full Prescribing Information for OPDIVO here.
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.
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Source: Bristol-Myers Squibb Company