Approval follows accelerated assessment by
Committee for Medicinal Products for Human Use, marking a rapid
pace in bringing a new option for patients with advanced
melanoma
Approval based on CheckMate -066 trial
demonstrating superior overall survival vs. dacarbazine in the
first-line setting and CheckMate -037 trial showing improved
response vs. chemotherapy in previously-treated patients, both at a
consistent and well-established dose
Opdivo safety profile is consistent with
previously-reported trials
Bristol-Myers Squibb Company (NYSE:BMY) today announced that the
European Commission has approved Opdivo, a PD-1 immune checkpoint
inhibitor, for the treatment of advanced (unresectable or
metastatic) melanoma in adults, regardless of BRAF status. Today’s
approval allows for the marketing of Opdivo in all 28 Member States
of the EU. It follows an accelerated assessment by the Committee
for Medicinal Products for Human Use (CHMP), which was announced on
April 24, 2015. This accelerated assessment was given because
Opdivo qualified for the designation as a “medicinal product of
major interest from the point of view of public health and in
particular from the view point of therapeutic innovation.” Opdivo
is the only PD-1 immune checkpoint inhibitor to receive an
accelerated assessment in Europe, and is the first approval given
by the European Commission for a PD-1 inhibitor in any cancer.
The incidence of melanoma has continued to increase in almost
all European countries, with an estimated one in five patients
expected to develop metastatic, or advanced, disease. Historically,
prognosis for late-stage metastatic melanoma has been poor: the
average survival rate for stage IV is just six months with a
one-year mortality rate of 75%.
“At Bristol-Myers Squibb, we are continually focused on
developing new ways to transform the outlook for patients with some
of the hardest-to-treat and deadliest cancers,” said Emmanuel Blin,
senior vice president, head of commercialization, policy and
operations, Bristol-Myers Squibb. “We are pleased to bring the
first PD-1 immune checkpoint inhibitor to the European Union for
the treatment of advanced melanoma. We are working relentlessly and
at record-breaking speed to build upon our Immuno-Oncology science
to deliver new treatment options, with the goal of improving
long-term survival for patients.”
About CheckMate -066,
-037
The European Commission’s approval is based on data from two
Phase 3 studies (CheckMate -066, -037). Together, the trials
investigated Opdivo across treatment lines and mutational status
with a consistent dose of 3 mg/kg every two weeks that has been
well-established across the Phase 3 clinical development program
for Opdivo.
“The Phase 3 data supporting the approval of Opdivo demonstrates
both superior overall survival and response rate for
treatment-naïve patients with advanced melanoma, against the
standard of care,” said Dirk Schadendorf, M.D., professor, director
and chair, Clinic for Dermatology, University Hospital, Essen,
Germany. “It is an important step forward in offering a new option
for advanced melanoma patients in the European Union, especially
considering that long-term benefits have largely been elusive in
this treatment category.”
CheckMate -066 is a Phase 3 randomized, double-blind study
comparing Opdivo (n=210) to the chemotherapy dacarbazine
(DTIC) (n=208) in patients with treatment-naïve advanced melanoma.
It is the first Phase 3 trial of a PD-1 immune checkpoint inhibitor
to demonstrate superior overall survival (OS) in advanced melanoma,
demonstrating a one-year survival rate of 73% for Opdivo versus 42%
for DTIC, and there was a 58% decrease in the risk of death for
patients treated with Opdivo based on a hazard ratio of 0.42
(99.79% CI, 0.25-0.73; P<0.0001). Objective response rate (ORR)
also was significantly higher for Opdivo than DTIC (40% vs. 14%,
P<0.0001). The primary endpoint of this trial was OS. Secondary
endpoints included progression-free survival (PFS) and ORR by
RECIST v1.1 criteria.
Safety was reported in all patients treated in the Opdivo and
DTIC arms. Fewer discontinuations were observed with Opdivo than
DTIC (6.8% vs. 11.7%) as well as for treatment-related Grade 3/4
adverse events (AEs) (11.7% vs. 17.6%), which were managed using
established safety algorithms. The most common Opdivo
treatment-related AEs were fatigue (20%), pruritus (17%), and
nausea (16.5%). Common adverse events in the DTIC arm were
consistent with those in previous reports and included nausea
(41.5%), vomiting (21%), fatigue (15%), diarrhea (15%) and
hematological toxicities. No deaths were attributed to study drug
toxicity in either arm.
CheckMate -037 is a Phase 3 randomized, controlled open-label
study of Opdivo (n=272) versus investigator’s choice
chemotherapy (ICC) (n=133) -- either single-agent dacarbazine or
carboplatin plus paclitaxel -- in patients with advanced melanoma
who were previously treated with Yervoy (ipilimumab), and, if BRAF
mutation positive, a BRAF inhibitor. Co-primary endpoints of the
study are ORR and OS. In a planned interim analysis of ORR, an
improvement in ORR of 32% was seen in the Opdivo arm (95% CI,
23.5%-40.8%) versus 11% in the investigator’s choice chemotherapy
arm (95% CI, 3.5%-23.1%). A majority of responses (87%) were
ongoing in those patients administered Opdivo. Responses to Opdivo
were demonstrated in both patients with or without BRAF mutuation
and regardless of PD-L1 expression.
Safety was reported on all patients treated in the Opdivo
(n=268) and ICC (n=102) arms. The majority of Opdivo
treatment-related adverse events (AEs) were Grade 1/2 and managed
using recommended treatment algorithms. Grade 3/4 drug-related AEs
were less frequent for the Opdivo arm (9% vs. 31% of patients
treated with chemotherapy). Discontinuations due to drug-related
AEs of any grade occurred in 3% of Opdivo-treated patients and 7%
of patients administered ICC. There were no deaths related to study
drug toxicity.
The approval also was based on data from a Phase 1b study (Study
-003) in relapsed advanced or metastatic melanoma, which
demonstrated the first characterization of Opdivo benefit/risk in
advanced melanoma. Of the 306 previously-treated patients
enrolled in the study, 107 had melanoma and received Opdivo at
a dose of 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg,
3 mg/kg, or 10 mg/kg every two weeks for a maximum of
two years. In this patient population, objective response was
reported in 33 patients (31%) with a median duration of
response of 22.9 months
(95% CI: 17.0, NR). The median PFS
was 3.7 months (95% CI: 1.9, 9.3). The
median OS was 17.3 months
(95% CI: 12.5, 36.7), and the estimated OS rates
were 63% (95% CI: 53, 71) at one year, 48%
(95% CI: 38, 57) at two years, and 41%
(95% CI: 31, 51) at three years.
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 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. On December 22, 2014, the U.S.
Food and Drug Administration (FDA) granted its first approval for
Opdivo 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. On March 4, 2015, Opdivo received
its second FDA approval for the treatment of patients with
metastatic squamous non-small cell lung cancer (NSCLC) with
progression on or after platinum-based chemotherapy.
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
www.bms.com.
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. Melanoma is the ninth most common
cancer in Europe, with an estimated 100,000 new cases diagnosed
annually and more than 20,000 deaths.
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.
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 be 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20150619005638/en/
Bristol-Myers SquibbMedia:Carrie Fernandez,
215-859-2605carrie.fernandez@bms.comorInvestors:Ranya
Dajani, 609-252-5330ranya.dajani@bms.comorBill Szablewski,
609-252-5864william.szablewski@bms.com
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Mar 2024 to Apr 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Apr 2023 to Apr 2024