First approval of Opdivo in the United States
PRINCETON, N.J.--(BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE:BMY) today announced that the U.S. Food and
Drug Administration (FDA) approved Opdivo (nivolumab) injection,
for intravenous use. Opdivo is a human programmed death
receptor-1 (PD-1) blocking antibody 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. Metastatic melanoma is the deadliest form of skin cancer, and
despite recent advances, there are limited treatment options available
for patients who have been previously treated with approved agents.
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"Bristol-Myers Squibb is pleased to be able to offer an important new
option for patients who have progressed following treatment for
unresectable or metastatic melanoma, which is one of the most aggressive
forms of cancer," said Lamberto
Andreotti, chief executive officer, Bristol-Myers Squibb. "The
approval of Opdivo, the latest breakthrough medicine from our
immuno-oncology pipeline, demonstrates our company's commitment to
meeting the needs of these patients, and to leading advances in the
science of immuno-oncology."
Opdivo is associated with immune-mediated: pneumonitis, colitis,
hepatitis, nephritis and renal dysfunction, hypothyroidism and
hyperthyroidism, other adverse reactions; and embryofetal toxicity.
Please see the Important Safety Information section below.
The company expects to begin shipping Opdivo within one to two
weeks of today's approval.
Opdivo Delivered A Response Rate of 32%
Opdivo is the only PD-1 that has demonstrated efficacy in a Phase
3, pivotal clinical trial with advanced melanoma in patients who had
been previously treated and progressed with Yervoy and, if BRAF
mutation positive, a BRAF inhibitor. The efficacy of Opdivo was
evaluated based on a single-arm, non-comparative planned interim
analysis of the first 120 patients who received Opdivo with a
minimum of 6 months follow-up in the Phase 3 CheckMate -037 trial.
Opdivo achieved a 32% (95% CI: 23, 41) response rate (38/120)
with a dosing strength and frequency of 3 mg/kg intravenously over 60
minutes every 2 weeks. 3% of patients (4/120) achieved a complete
response, and 28% (34/120) achieved a partial response. Of 38 patients
with responses, 33 patients (87%) had ongoing responses with durability
of response ranging from 2.6+ to 10+ months, which included 13 patients
with ongoing responses of 6 months or longer. Responses to Opdivo
were demonstrated in both patients with and without BRAF mutation.
The safety profile of Opdivo has been demonstrated in the
pivotal, Phase 3 CheckMate-037 trial. 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. The most
common adverse reaction (>=20%) reported with Opdivo was rash
(21%). Please see the Important Safety Information section
below.
"The approval of Opdivo gives patients and physicians an
important new treatment option for a population where they were once
very limited," said Jeffrey S. Weber, MD, Ph.D., director of the Donald
A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer
Center. "For the first time, a PD-1 blocking antibody has shown a
response rate of 32% in a Phase 3 randomized clinical trial of patients
with unresectable or metastatic melanoma, who have progressed following
first line therapy." Efficacy was evaluated in a single-arm,
non-comparative, planned interim analysis of the first 120 patients who
received Opdivo in the CheckMate -037 trial in whom the minimum
duration of follow up was 6 months.
"The emergence of effective immuno-oncology therapies that are capable
of successfully treating metastatic melanoma has reinvigorated the field
of cancer immunology with an optimism that immune based treatments will
play a central role in therapeutic strategies for cancer patients," said
Jill O'Donnell-Tormey, Ph.D., CEO and director of Scientific Affairs at
the Cancer Research Institute, a nonprofit organization dedicated to
advancing the science of cancer immunology.
About the CheckMate -037 Trial
CheckMate -037 was a randomized, Phase 3 trial evaluating Opdivo
3 mg/kg (n=268), administered every two weeks, or chemotherapy (n=102)
(investigator's choice of either single-agent dacarbazine 1000 mg/m2
every 3 weeks or the combination of carboplatin AUC 6 every 3 weeks plus
paclitaxel 175 mg/m2 every 3 weeks) in patients with advanced melanoma
who had been previously treated and progressed with Yervoy and,
if BRAF mutation positive, a BRAF inhibitor. No premedication is
required with Opdivo.
The primary objective of this analysis of the CheckMate -037 trial was
Objective Response Rate (ORR). CheckMate -037 included 90 participating
trial sites in 14 countries, and included both institutional and
community practice centers. The clinical study is ongoing to determine
whether there is an overall survival benefit.
In the Opdivo treated patients (n=120), 76% of patients had M1C
disease, 18% of patients had a history of brain metastases, and 56% of
patients had elevated LDH levels. The median age of patients was 58. 22%
of patients were BRAF V600 mutation positive.
Distinct Immune Pathway
Opdivo is approved for use in patients previously treated with Yervoy.
Although both treatments are immunotherapies, PD-1 and CTLA-4 are
distinct pathways.
About Bristol-Myers Squibb's Support Programs for Opdivo
As the leader in metastatic melanoma, Bristol-Myers Squibb remains
committed to helping patients through treatment with Opdivo. For
support and assistance, patients and physicians may call 1-855-OPDIVO-1.
This number offers one-stop access to a range of support services for
patients and healthcare professionals alike.
About Bristol-Myers Squibb's Access Support
Bristol-Myers Squibb is committed to helping patients access Opdivo
and offers numerous programs to support patient and providers in gaining
access. BMS Access Support(R), the Bristol-Myers Squibb
Reimbursement Services program, is designed to support access to BMS
medicines and expedite time to therapy through reimbursement support
including Benefit Investigations, Prior Authorization Facilitation,
Appeals Assistance, and assistance for patient out-of-pocket costs. BMS
Access Support assists patients and providers throughout the treatment
journey - whether it is at initial diagnosis or in support of transition
from a clinical trial. More information about our reimbursement support
services can be obtained by calling 1-800-861-0048 or by visiting www.bmsaccesssupport.com.
For healthcare providers seeking Opdivo specific reimbursement
information, please visit the BMS Access Support Product section by
visiting www.bmsaccesssupportoncology.com.
About the Opdivo Clinical Development Program
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.
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
574 patients with solid tumors, fatal immune-mediated pneumonitis
occurred in 0.9% (5/574) 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
-- In Trial 1, the following clinically significant, immune-mediated
adverse reactions occurred in less than 1% of OPDIVO-treated patients:
pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal
insufficiency, and facial and abducens nerve paresis. 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,
Guillian-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 Metastatic 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
2014, an estimated 76,100 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 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.
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Source: Bristol-Myers Squibb Company
Media:
Sarah Koenig, 609-252-4145
sarah.koenig@bms.com
or
Carrie Fernandez, 609-419-5448
carrie.fernandez@bms.com
or
Christina Trank, 609-419-5497
christina.trank@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
or
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com