U.S. Food & Drug Administration Extends Action Date for Supplemental Biologics License Application for Opdivo (nivolumab) in ...
August 12 2015 - 4:15PM
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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version on businesswire.com: http://www.businesswire.com/news/home/20150812006233/en/
Bristol-Myers Squibb CompanyMedia:Carrie Fernandez,
609-419-5448, Cell: 215-859-2605,
carrie.fernandez@bms.comorInvestors:Ranya Dajani,
609-252-5330, ranya.dajani@bms.comBill Szablewski, 609-252-5864,
william.szablewski@bms.com
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