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/
Seattle GeneticsInvestors:Peggy Pinkston,
425-527-4160ppinkston@seagen.comMedia:Tricia Larson,
425-527-4180tlarson@seagen.comorBristol-Myers
SquibbMedia:Ken Dominski,
609-252-5251ken.dominski@bms.comInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.comRyan Asay,
609-252-5020ryan.asay@bms.com
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