Seattle
Genetics, Inc. (Nasdaq:SGEN) and Bristol-Myers
Squibb Company (NYSE:BMY) today announced that the companies have
entered into a clinical trial collaboration agreement to evaluate the
investigational combination of Seattle Genetics’ antibody-drug conjugate
(ADC) Adcetris (brentuximab vedotin) and Bristol-Myers Squibb’s
immunotherapy Opdivo (nivolumab) in two planned Phase 1/2
clinical trials. The first trial will evaluate the combination of Adcetris
and Opdivo as a potential treatment option for patients with
relapsed or refractory Hodgkin lymphoma (HL), and the second trial will
focus on patients with relapsed or refractory B-cell and T-cell
non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma
(DLBCL).
Adcetris is an ADC directed to CD30, a defining marker of
classical HL, which combines the targeting ability of a monoclonal
antibody with the potency of a cell-killing agent. Opdivo is a
human programmed death receptor-1 (PD-1) blocking antibody that binds to
the PD-1 receptor expressed on activated T-cells.
“This collaboration will expand our broad Adcetris clinical
development program towards our goal of improving outcomes for patients
with Hodgkin lymphoma and other CD30-expressing malignancies,” said Clay
B. Siegall, Ph.D., President and Chief Executive Officer of Seattle
Genetics. “Ultimately, our vision is to advance the treatment of cancer
by exploring more targeted treatment approaches that result in enhanced
activity, reduced toxicities and improved long-term results for
patients. We look forward to working with Bristol-Myers Squibb to define
the activity and tolerability of adding Opdivo to Adcetris,
and informing this potential treatment strategy in hematologic
malignancies.”
“Bristol-Myers Squibb continues to strengthen its broad development
program for Opdivo through collaborations that explore novel
combination regimens in areas of serious unmet need,” said Michael
Giordano, senior vice president, Head of Development, Oncology,
Bristol-Myers Squibb. “We are pleased to collaborate with Seattle
Genetics on clinical research focused on hematologic malignancies.”
The studies are expected to begin in 2015, with Seattle Genetics
conducting the HL trial and Bristol-Myers Squibb conducting the NHL
trial. Additional details of the collaboration were not disclosed.
Adcetris is approved in relapsed HL and systemic anaplastic large
cell lymphoma (ALCL) but is not currently approved for the treatment of
relapsed, transplant eligible HL or for the treatment of other types of
NHL. Opdivo is currently not approved for the treatment of
lymphoma.
About ADCETRIS® (Brentuximab Vedotin)
Adcetris is an ADC comprising an anti-CD30 monoclonal antibody
attached by a protease-cleavable linker to a microtubule disrupting
agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’
proprietary technology. The ADC employs a linker system that is designed
to be stable in the bloodstream but to release MMAE upon internalization
into CD30-expressing tumor cells.
Seattle Genetics and Takeda are jointly developing Adcetris.
Under the terms of the collaboration agreement, Seattle Genetics has
U.S. and Canadian commercialization rights and Takeda has rights to
commercialize Adcetris in the rest of the world. Seattle Genetics
and Takeda are funding joint development costs for Adcetris on a
50:50 basis, except in Japan where Takeda will be solely responsible for
development costs. Adcetris has received marketing authorization
by regulatory authorities in more than 45 countries. In addition, Adcetris
is being evaluated as an investigational agent in more than 30 ongoing
clinical trials, including four phase 3 studies, across a variety of
CD30-expressing malignances including HL.
About OPDIVO (Nivolumab)
The U.S. Food and Drug Administration (FDA) approved Opdivo (nivolumab)
injection, for intravenous use. Opdivo is a 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. 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. The FDA granted Opdivo Breakthrough Therapy
Designation in May 2014 for the treatment of patients with HL after
failure of autologous stem cell transplant and brentuximab vedotin.
About Lymphoma
Lymphoma is a general term for a group of cancers that originate in the
lymphatic system. There are two major categories of lymphoma: HL and
NHL. NHL is further categorized into indolent (low-grade) or aggressive,
including DLBCL. DLBCL is the most common type of NHL. HL is
distinguished from other types of lymphoma by the presence of one
characteristic type of cell, known as the Reed-Sternberg cell. The
Reed-Sternberg cell generally expresses CD30.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development
and commercialization of innovative antibody-based therapies for the
treatment of cancer. Seattle Genetics is leading the field in developing
antibody-drug conjugates (ADCs), a technology designed to harness the
targeting ability of antibodies to deliver cell-killing agents directly
to cancer cells. The company’s lead product, ADCETRIS®
(brentuximab vedotin) is an ADC that, in collaboration with Takeda
Pharmaceutical Company Limited, is commercially available for two
indications in more than 45 countries, including the U.S., Canada, Japan
and members of the European Union. Additionally, ADCETRIS is being
evaluated broadly in more than 30 ongoing clinical trials. Seattle
Genetics is also advancing a robust pipeline of clinical-stage ADC
programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME
and ASG-15ME. Seattle Genetics has collaborations for its ADC technology
with a number of leading biotechnology and pharmaceutical companies,
including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech,
GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.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.
ADCETRIS (BRENTUXIMAB VEDOTIN) U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death can occur in patients receiving ADCETRIS.
Contraindication:
ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary
toxicity (e.g., interstitial infiltration and/or inflammation).
Warnings and Precautions:
-
Peripheral neuropathy: ADCETRIS treatment causes a peripheral
neuropathy that is predominantly sensory. Cases of peripheral motor
neuropathy have also been reported. ADCETRIS-induced peripheral
neuropathy is cumulative. Monitor patients for symptoms of neuropathy,
such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a
burning sensation, neuropathic pain or weakness and institute dose
modifications accordingly.
-
Anaphylaxis and infusion reactions: Infusion-related reactions,
including anaphylaxis, have occurred with ADCETRIS. Monitor patients
during infusion. If an infusion-related reaction occurs, interrupt the
infusion and institute appropriate medical management. If anaphylaxis
occurs, immediately and permanently discontinue the infusion and
administer appropriate medical therapy.
-
Hematologic toxicities: Prolonged (≥1 week) severe neutropenia
and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Febrile neutropenia has been reported with ADCETRIS. Monitor complete
blood counts prior to each dose of ADCETRIS and consider more frequent
monitoring for patients with Grade 3 or 4 neutropenia. Monitor
patients for fever. If Grade 3 or 4 neutropenia develops, consider
dose delays, reductions, discontinuation, or G-CSF prophylaxis with
subsequent doses.
-
Serious infections and opportunistic infections: Infections
such as pneumonia, bacteremia, and sepsis or septic shock (including
fatal outcomes) have been reported in patients treated with ADCETRIS.
Closely monitor patients during treatment for the emergence of
possible bacterial, fungal or viral infections.
-
Tumor lysis syndrome: Closely monitor patients with rapidly
proliferating tumor and high tumor burden.
-
Increased toxicity in the presence of severe renal impairment: The
frequency of ≥Grade 3 adverse reactions and deaths was greater in
patients with severe renal impairment compared to patients with normal
renal function. Avoid the use of ADCETRIS in patients with severe
renal impairment.
-
Increased toxicity in the presence of moderate or severe hepatic
impairment: The frequency of ≥Grade 3 adverse reactions and deaths
was greater in patients with moderate or severe hepatic impairment
compared to patients with normal hepatic function. Avoid the use of
ADCETRIS in patients with moderate or severe hepatic impairment.
-
Hepatotoxicity: Serious cases of hepatotoxicity, including
fatal outcomes, have occurred with ADCETRIS. Cases were consistent
with hepatocellular injury, including elevations of transaminases
and/or bilirubin, and occurred after the first dose of ADCETRIS or
rechallenge. Preexisting liver disease, elevated baseline liver
enzymes, and concomitant medications may also increase the risk.
Monitor liver enzymes and bilirubin. Patients experiencing new,
worsening, or recurrent hepatotoxicity may require a delay, change in
dose, or discontinuation of ADCETRIS.
-
Progressive multifocal leukoencephalopathy (PML): JC virus
infection resulting in PML and death has been reported in
ADCETRIS-treated patients. In addition to ADCETRIS therapy, other
possible contributory factors include prior therapies and underlying
disease that may cause immunosuppression. Consider the diagnosis of
PML in any patient presenting with new-onset signs and symptoms of
central nervous system abnormalities. Hold ADCETRIS if PML is
suspected and discontinue ADCETRIS if PML is confirmed.
-
Serious dermatologic reactions: Stevens-Johnson syndrome (SJS)
and toxic epidermal necrolysis (TEN), including fatal outcomes, have
been reported with ADCETRIS. If SJS or TEN occurs, discontinue
ADCETRIS and administer appropriate medical therapy.
-
Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant
women of the potential hazard to the fetus.
Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2
trials. Across both trials, the most common adverse reactions (≥20%),
regardless of causality, were neutropenia, peripheral sensory
neuropathy, fatigue, nausea, anemia, upper respiratory tract infection,
diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Drug Interactions:
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp
inhibitors, has the potential to affect the exposure to monomethyl
auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse reactions are increased in patients with
moderate or severe hepatic impairment or severe renal impairment. Avoid
use.
For additional important safety information, including Boxed WARNING,
please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com.
OPDIVO 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.
Seattle Genetics Forward-Looking Statement
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the future potential
therapeutic uses of Adcetris (including in combination with Opdivo) and
future clinical and regulatory progress. Actual results or developments
may differ materially from those projected or implied in these
forward-looking statements. Factors that may cause such a difference
include risks related to adverse clinical results associated with the
use of Adcetris or Opdivo (or the combination), the failure of the
companies to continue their collaboration or execute on the planned
clinical trials or adverse regulatory action. More information about the
risks and uncertainties faced by Seattle Genetics is contained in the
Company’s quarterly report on Form 10-Q for the quarter ended September
30, 2014 filed with the Securities and Exchange Commission. Seattle
Genetics disclaims any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information,
future events or otherwise.
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 this investigational
combination regimen will receive regulatory approval, or, if approved,
that it will become 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, 2013 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.
Photos/Multimedia Gallery Available: http://www.businesswire.com/multimedia/home/20150112005188/en/
Copyright Business Wire 2015