Kyowa Hakko Kirin & Bristol-Myers Squibb Announce Immuno-Oncology Clinical Collaboration Studying Mogamulizumab & Opdivo (niv...
July 29 2015 - 7:00PM
Business Wire
Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151,“Kyowa Hakko Kirin”)
and Bristol-Myers Squibb Company (NYSE:BMY, “Bristol-Myers Squibb”)
today announced that the companies have entered into a clinical
trial collaboration agreement to conduct a Phase 1/2 combination
study with mogamulizumab, an anti-CCR4 antibody and Opdivo
(nivolumab), a PD-1 immune checkpoint inhibitor. The study, which
will be conducted in the U.S., will focus on evaluating the safety,
tolerability and anti-tumor activity of combining mogamulizumab and
Opdivo as a potential treatment option for patients with advanced
or metastatic solid tumors. Prior to this agreement, Kyowa Hakko
Kirin, Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd.
(Tokyo: 4528) entered into a clinical trial collaboration agreement
to study the combination of mogamulizumab and Opdivo in Japan.
Mogamulizumab and Opdivo are part of a new class of cancer
treatments known as immunotherapies, which are designed to harness
the body’s own immune system in fighting cancer by targeting
distinct regulatory components of the immune system.
“We are pleased to conduct a combination study with
Bristol-Myers Squibb not only in Japan but also in the U.S.,” said
Yoichi Sato, Director of the Board Managing Executive Officer, Vice
President, Head of Research and Development Division of Kyowa Hakko
Kirin. “We believe that the planned combination of these two
immunotherapies has the potential to deliver better outcomes in
patients with advanced cancers than existing treatments.”
“Today’s agreement builds on our initial collaboration with
Kyowa Hakko Kirin in Japan, which includes our partner Ono
Pharmaceutical Co., Ltd., and is the latest example of our
continued commitment to evaluating the potential of combination
immuno-oncology regimens for patients with metastatic cancer,”
stated Michael Giordano, senior vice president, Head of
Development, Oncology, Bristol-Myers Squibb.
The study will be conducted by Kyowa Hakko Kirin. Additional
details of the collaboration were not disclosed.
About Mogamulizumab
Mogamulizumab (Brand name: POTELIGEO®) is a novel, humanized mAb
directed against CC chemokine receptor type 4 (CCR4). Engineered by
Kyowa Hakko Kirin's unique POTELLIGENT® Technology, the antibody is
designed to kill its target cells through potent antibody-dependent
cellular cytotoxicity. Mogamulizumab was launched in Japan in May
2012 for the treatment of patients with relapsed or refractory
CCR4-positive adult T-cell leukemia-lymphoma (ATL). The drug was
approved for indication expansion and was granted marketing
authorization in Japan for the treatment of patients with relapsed
or refractory CCR4-positive, peripheral T-cell lymphoma (PTCL) and
cutaneous T-cell lymphoma (CTCL) in March 2014, and with
chemotherapy-native CCR4-positive ATL in December 2014. Clinical
trials with mogamulizumab are ongoing in the US, EU and other
countries.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor that has received approval from the U.S. Food and Drug
Administration (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.
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.
About Kyowa Hakko Kirin
Kyowa Hakko Kirin is a leading biopharmaceutical company in
Japan focusing on its core business area of oncology, nephrology
and immunology/allergy. Kyowa Hakko Kirin leverages
antibody-related leading-edge technologies to discover and develop
innovative new drugs aiming to become a global specialty
pharmaceutical company which contributes to the health and
well-being of people around the world. For more information, visit
http://www.kyowa-kirin.com.
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, please 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 the study combining mogamulizumab and Opdivo will be
successful. 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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609-252-5330ranya.dajani@bms.comorKyowa Hakko
KirinMedia:Public Relations Group, Corporate
Communication
Dept.+81-3-3282-1903media@kyowa-kirin.co.jporInvestors:Investor
Relation Group, Corporate Communication
Dept.+81-3-3282-0009ir@kyowa-kirin.co.jp
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