– Data will be presented in an oral session at
the annual American Society of Hematology (ASH) meeting on
Saturday, December 3 at 2:15 p.m. PT –
– Trial achieved highly statistically
significant improvements in rate of objective response lasting at
least four months, median progression-free survival and overall
response rate, and decrease in symptom burden in ADCETRIS arm;
Safety profile associated with ADCETRIS was generally consistent
with the existing prescribing information –
Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc.
(NASDAQ: SGEN) today announced that data from the Phase 3 ALCANZA
clinical trial evaluating ADCETRIS (brentuximab vedotin) in
patients with cutaneous T-cell lymphoma (CTCL) will be presented in
an oral session at the 58th American Society of Hematology (ASH)
annual meeting on Saturday, December 3 at 2:15 p.m. PT. Topline
data were reported in August 2016 demonstrating the ALCANZA trial
met its primary endpoint of achieving a highly statistically
significant improvement in the rate of objective response lasting
at least four months (ORR4). Based on the study results, the U.S.
Food and Drug Administration (FDA) granted Breakthrough Therapy
Designation to ADCETRIS for the treatment of the most common
subtypes of CTCL, mycosis fungoides (MF) and primary cutaneous
anaplastic large cell lymphoma (pcALCL). ADCETRIS is an
antibody-drug conjugate (ADC) directed to CD30 which is expressed
on skin lesions in approximately 50 percent of patients with CTCL.
ADCETRIS is currently not approved for the treatment of CTCL.
This Smart News Release features multimedia.
View the full release here:
http://www.businesswire.com/news/home/20161203005007/en/
“CTCL is an incurable disease that severely impacts a patient’s
quality of life and has a poor prognosis in advanced stages. The
systemic therapies currently approved for treatment rarely provide
reliable and durable responses, and to-date, no investigational
systemic therapies have shown outcomes superior to standard of care
therapies such as methotrexate or bexarotene in any clinical
trials,” said Youn H. Kim, M.D., Stanford University School of
Medicine, Stanford, Calif. “This is the first randomized Phase 3
clinical trial evaluating a novel agent versus standard of care
options, including methotrexate or bexarotene, in CTCL. Data from
the ALCANZA Phase 3 trial provide compelling evidence demonstrating
that patients treated with ADCETRIS benefited in the clinical
outcomes assessed in the study compared to the patients in the
control arm treated with a standard of care agent. ADCETRIS was
generally well-tolerated, consistent with prior studies, and the
most common adverse event, peripheral neuropathy, was manageable
with a modest rate of treatment discontinuation.”
“The data from the ALCANZA trial presented at this year’s ASH
meeting provide evidence of the potential benefit of ADCETRIS in
treating patients with CD30-positive CTCL. For patients with CTCL,
there is a significant need for additional treatment options that
increase the opportunity to achieve durable responses,” said Dirk
Huebner, M.D., Executive Medical Director, Oncology Therapeutic
Area Unit, Takeda Pharmaceutical Company. “The ALCANZA trial
achieved its primary and secondary endpoints, all of which were
highly statistically significant in favor of ADCETRIS. Treatment
with ADCETRIS demonstrated a highly statistically significant
improvement over the control arm in objective response rate lasting
at least four months of 56.3 percent versus 12.5 percent and median
progression-free survival of 16.7 months versus 3.5 months. Safety
data were consistent with the currently approved label. We look
forward to working with regulatory bodies around the world to bring
a potential new treatment option to patients with CTCL.”
“The data from the Phase 3 ALCANZA clinical trial presented at
ASH highlight improvements in the efficacy measurements experienced
by the ADCETRIS treated patients with CD30-expressing CTCL over the
standard of care agents methotrexate or bexarotene utilized in the
control arm,” said Jonathan Drachman, M.D., Chief Medical Officer
and Executive Vice President, Research and Development of Seattle
Genetics. “The ALCANZA clinical trial represents the fourth
consecutive registrational trial with a positive outcome for
ADCETRIS, which we are evaluating broadly as the foundation of care
for CD30-expressing lymphomas. Based on the results of this trial,
the FDA has granted Breakthrough Therapy Designation and we plan to
submit a supplemental Biologics License Application in the first
half of 2017 for approval in this setting.”
Brentuximab Vedotin Demonstrates Significantly Superior
Clinical Outcomes in Patients with CD30-Expressing Cutaneous T Cell
Lymphoma Versus Physician's Choice (Methotrexate or Bexarotene):
The Phase 3 ALCANZA Study (Abstract #182, oral presentation at 2:15
p.m. PT on December 3, 2016 at the San Diego Convention Center,
Room 6AB)
Key findings, which will be presented by Dr. Youn Kim, Stanford
University, include:
- The trial achieved its primary endpoint
and the ADCETRIS treatment arm demonstrated a highly statistically
significant improvement in the ORR4 versus the control arm as
assessed by an independent review facility. The ORR4 was 56.3
percent in the ADCETRIS arm compared to 12.5 percent in the control
arm (p-value <0.0001).
- The key secondary endpoints specified
in the protocol, including complete response (CR) rate,
progression-free survival (PFS) and reduction in the burden of
symptoms during treatment (per Skindex-29), were all highly
statistically significant in favor of the ADCETRIS arm.
- The median PFS in the ADCETRIS arm was
16.7 months compared to 3.5 months in the control arm (HR 0.270;
95% CI, 0.169, 0.430; p-value <0.0001).
- The CR rate in the ADCETRIS arm was
15.6 percent compared to 1.6 percent in the control arm (p-value =
0.0046).
- The Skindex-29 symptom domain showed a
mean max reduction of -27.96 in the ADCETRIS arm compared to -8.62
in the control arm (p-value <0.0001). There was a difference in
mean maximum reduction of -18.9 (95% CI, -26.6, -11.2).
- Patients received a median of 12 cycles
(36 weeks) of ADCETRIS versus 17 weeks of bexarotene or nine weeks
of methotrexate.
- The safety profile associated with
ADCETRIS from the ALCANZA trial was generally consistent with the
existing prescribing information.
- The most common adverse events of any
grade occurring in 15 percent or more of patients in the ADCETRIS
and control arms were: peripheral neuropathy (67 and six percent,
respectively), nausea (36 and 13 percent, respectively), diarrhea
(29 and six percent, respectively), fatigue (29 and 27 percent,
respectively), vomiting (17 and five percent, respectively),
alopecia (15 and three percent, respectively), pruritis (17 and 13
percent respectively), pyrexia (17 and 18 percent, respectively),
decreased appetite (15 and five percent, respectively) and
hypertriglyceridemia (two and 18 percent, respectively). In the
ADCETRIS arm, the most common grade 3 or 4 events were peripheral
sensory neuropathy (no grade 4 events), fatigue, diarrhea, nausea,
vomiting and pruritis. In the control arm, the most common grade 3
or 4 events were hypertriglyceridemia, pruritis, fatigue and
pyrexia.
- The majority of the peripheral
neuropathy events were grade 1 or 2 (26 percent and 32 percent,
respectively). Peripheral neuropathy events were observed in nine
percent at grade 3 and no grade 4 events were reported. Eighty-two
percent of patients reported resolution or improvement in
peripheral neuropathy events in the ADCETRIS arm at a median of
22.9 months of follow-up.
- Discontinuation due to adverse events
occurred in 24 percent of patients in the ADCETRIS arm compared to
eight percent in the control arm. Serious adverse events were
comparable between the ADCETRIS arm and the control arm (29 percent
in each). Four deaths in the ADCETRIS arm (three unrelated to study
drug) occurred within 30 days of the last dose.
ALCANZA Trial Design
- ALCANZA is a randomized, open-label
Phase 3 study designed to evaluate single-agent ADCETRIS versus a
control arm of investigator’s choice of standard of care therapies,
methotrexate or bexarotene, in patients with CD30-positive CTCL,
including those with pcALCL or MF.
- The primary endpoint is ORR4 as
assessed by Global Response Score in the ADCETRIS arm compared to
the control arm. The results of the trial were assessed by an
independent review facility.
- Key secondary endpoints are CR rate,
PFS and reduction in the burden of symptoms during treatment.
- Patients with pcALCL must have received
at least one prior systemic or radiation therapy and patients with
MF must have received at least one prior systemic therapy.
- A total of 131 patients were randomized
with 128 patients in the intent-to-treat population. Sixty-four
patients were assigned to the ADCETRIS arm and 64 patients were
assigned to the control arm.
- Patients received ADCETRIS every three
weeks versus investigator’s choice of bexarotene or methotrexate
for up to approximately one year.
- This international multi-center trial
was conducted across 52 sites in North and South America, Europe
and Australia under operational responsibility of Takeda
Pharmaceuticals.
The ALCANZA trial received a Special Protocol Assessment (SPA)
agreement from the FDA and scientific advice from the European
Medicines Agency (EMA). Seattle Genetics plans to submit a
supplemental Biologics License Application to the FDA in the first
half of 2017. Takeda plans to begin to submit data from the ALCANZA
trial to regulatory agencies in its territories in 2017.
About CTCLLymphoma is a general term for a group of
cancers that originate in the lymphatic system. There are two major
categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma.
Cutaneous lymphomas are a category of non-Hodgkin lymphoma that
primarily involve the skin. According to the Cutaneous Lymphoma
Foundation, CTCL is the most common type of cutaneous lymphoma and
typically presents with red, scaly patches or thickened plaques of
skin that often mimic eczema or chronic dermatitis. Progression
from limited skin involvement may be accompanied by skin tumor
formation, ulceration and exfoliation, complicated by itching and
infections. Advanced stages are defined by involvement of lymph
nodes, peripheral blood and internal organs. According to published
literature, CD30 is expressed on skin lesions in approximately 50
percent of CTCL patients.
The standard treatment for systemically pretreated CTCL includes
skin-directed therapies, radiation and systemic therapies. The
systemic therapies currently approved for treatment have
demonstrated 30 to 45 percent objective response rates, with low
complete response rates.
About ADCETRISADCETRIS is being evaluated broadly in more
than 70 ongoing clinical trials, including three Phase 3 studies,
the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma
and the ongoing ECHELON-2 trial in frontline mature T-cell
lymphomas, as well as the completed ALCANZA trial in cutaneous
T-cell lymphoma for which a supplemental BLA is planned in the
first half of 2017. ADCETRIS is also being evaluated in many
additional types of CD30-positive malignancies, including B-cell
lymphomas.
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-positive tumor cells.
ADCETRIS for intravenous injection has received approval from
the FDA for three indications: (1) regular approval for the
treatment of patients with classical Hodgkin lymphoma after failure
of autologous hematopoietic stem cell transplantation (auto-HSCT)
or after failure of at least two prior multi-agent chemotherapy
regimens in patients who are not auto-HSCT candidates, (2) regular
approval for the treatment of classical Hodgkin lymphoma patients
at high risk of relapse or progression as post-auto-HSCT
consolidation, and (3) accelerated approval for the treatment of
patients with systemic anaplastic large cell lymphoma (sALCL) after
failure of at least one prior multi-agent chemotherapy regimen. The
sALCL indication is approved under accelerated approval based on
overall response rate. Continued approval for the sALCL indication
may be contingent upon verification and description of clinical
benefit in confirmatory trials. Health Canada granted ADCETRIS
approval with conditions for relapsed or refractory Hodgkin
lymphoma and sALCL.
ADCETRIS was granted conditional marketing authorization by the
European Commission in October 2012 for two indications: (1) for
the treatment of adult patients with relapsed or refractory
CD30-positive Hodgkin lymphoma following autologous stem cell
transplant (ASCT), or following at least two prior therapies when
ASCT or multi-agent chemotherapy is not a treatment option, and (2)
the treatment of adult patients with relapsed or refractory sALCL.
ADCETRIS has received marketing authorization by regulatory
authorities in 65 countries for relapsed or refractory Hodgkin
lymphoma and sALCL.
In June 2016, the European Commission extended the current
conditional marketing authorization of ADCETRIS and approved
ADCETRIS for the treatment of adult patients with CD30-positive
Hodgkin lymphoma at increased risk of relapse or progression
following ASCT. See important safety information below.
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 is solely
responsible for development costs.
About Takeda Pharmaceutical CompanyTakeda Pharmaceutical
Company Limited is a global, research and development-driven
pharmaceutical company committed to bringing better health and a
brighter future to patients by translating science into
life-changing medicines. Takeda focuses its R&D efforts on
oncology, gastroenterology and central nervous system therapeutic
areas plus vaccines. Takeda conducts R&D both internally and
with partners to stay at the leading edge of innovation. New
innovative products, especially in oncology and gastroenterology,
as well as our presence in Emerging Markets, fuel the growth of
Takeda. More than 30,000 Takeda employees are committed to
improving quality of life for patients, working with our partners
in health care in more than 70 countries. For more information,
visit http://www.takeda.com/news.
Additional information about Takeda is available through its
corporate website, www.takeda.com, and additional information about
Takeda Oncology, the brand for the global oncology business unit of
Takeda Pharmaceutical Company Limited, is available through its
website, www.takedaoncology.com.
About Seattle GeneticsSeattle Genetics is an innovative
biotechnology company that develops and commercializes novel
antibody-based therapies for the treatment of cancer. The company’s
industry-leading antibody-drug conjugate (ADC) technology harnesses
the targeting ability of antibodies to deliver cell-killing agents
directly to cancer cells. ADCETRIS® (brentuximab vedotin), the
company’s lead product, in collaboration with Takeda Pharmaceutical
Company Limited, is the first in a new class of ADCs commercially
available globally in 65 countries for relapsed classical Hodgkin
lymphoma and relapsed systemic anaplastic large cell lymphoma
(sALCL). Seattle Genetics is also advancing vadastuximab talirine
(SGN-CD33A; 33A), an ADC in a Phase 3 trial for acute myeloid
leukemia. Headquartered in Bothell, Washington, Seattle Genetics is
developing a robust pipeline of innovative therapies for
blood-related cancers and solid tumors designed to address
significant unmet medical needs and improve treatment outcomes for
patients. The company has collaborations for its proprietary ADC
technology with a number of companies including AbbVie, Astellas,
Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can
be found at www.seattlegenetics.com
ADCETRIS (brentuximab vedotin) Global Important Safety
Information
Active Ingredient: brentuximab vedotin
Please refer to Summary of Product Characteristics (SmPC) before
prescribing.
INDICATIONSADCETRIS® is indicated for the treatment of
adult patients with relapsed or refractory CD30+ Hodgkin lymphoma
(HL):
1. following autologous stem cell transplant (ASCT) or
2. following at least two prior therapies when ASCT or
multi-agent chemotherapy is not a treatment option.
ADCETRIS is indicated for the treatment of adult patients with
CD30+ HL at increased risk of relapse or progression following
ASCT.
ADCETRIS is indicated for the treatment of adult patients with
relapsed or refractory systemic anaplastic large cell lymphoma
(sALCL).
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
ADCETRIS is contraindicated for patients with hypersensitivity
to brentuximab vedotin and its excipients. In addition, combined
use of ADCETRIS with bleomycin is contraindicated as it causes
pulmonary toxicity.
SPECIAL WARNINGS & PRECAUTIONS
Progressive multifocal leukoencephalopathy (PML): John
Cunningham virus (JCV) reactivation resulting in PML and death can
occur in patients treated with ADCETRIS. PML has been reported in
patients who received ADCETRIS after receiving multiple prior
chemotherapy regimens.
Patients should be closely monitored for new or worsening
neurological, cognitive, or behavioral signs or symptoms, which may
be suggestive of PML. Suggested evaluation of PML includes
neurology consultation, gadolinium-enhanced magnetic resonance
imaging of the brain, and cerebrospinal fluid analysis for JCV DNA
by polymerase chain reaction or a brain biopsy with evidence of
JCV. ADCETRIS dosing should be held for any suspected case of PML
and should be permanently discontinued if a diagnosis of PML is
confirmed.
Pancreatitis: Acute pancreatitis has been observed in
patients treated with ADCETRIS. Fatal outcomes have been reported.
Patients should be closely monitored for new or worsening abdominal
pain, which may be suggestive of acute pancreatitis. Patient
evaluation may include physical examination, laboratory evaluation
for serum amylase and serum lipase, and abdominal imaging, such as
ultrasound and other appropriate diagnostic measures. ADCETRIS
should be held for any suspected case of acute pancreatitis.
ADCETRIS should be discontinued if a diagnosis of acute
pancreatitis is confirmed.
Pulmonary Toxicity: Cases of pulmonary toxicity, some
with fatal outcomes, have been reported in patients receiving
ADCETRIS. Although a causal association with ADCETRIS has not been
established, the risk of pulmonary toxicity cannot be ruled out.
New or worsening pulmonary symptoms should be promptly evaluated
and treated appropriately.
Serious infections and opportunistic infections: Serious
infections such as pneumonia, staphylococcal bacteremia,
sepsis/septic shock (including fatal outcomes), and herpes zoster,
and opportunistic infections such as Pneumocystis jiroveci
pneumonia and oral candidiasis have been reported in patients
treated with ADCETRIS. Patients should be carefully monitored
during treatment for emergence of possible serious and
opportunistic infections.
Infusion-related reactions (IRR): Immediate and delayed
IRR, as well as anaphylaxis, have occurred with ADCETRIS. Patients
should be carefully monitored during and after an infusion. If
anaphylaxis occurs, administration of ADCETRIS should be
immediately and permanently discontinued and appropriate medical
therapy should be administered. If an IRR occurs, the infusion
should be interrupted and appropriate medical management
instituted. The infusion may be restarted at a slower rate after
symptom resolution. Patients who have experienced a prior IRR
should be premedicated for subsequent infusions. IRRs are more
frequent and more severe in patients with antibodies to
ADCETRIS.
Tumor lysis syndrome (TLS): TLS has been reported with
ADCETRIS. Patients with rapidly proliferating tumor and high tumor
burden are at risk of TLS. These patients should be monitored
closely and managed according to best medical practice.
Peripheral neuropathy (PN): ADCETRIS treatment may cause
PN, both sensory and motor. ADCETRIS-induced PN is typically
cumulative and reversible in most cases. Patients should be
monitored for symptoms of PN, such as hypoesthesia, hyperesthesia,
paresthesia, discomfort, a burning sensation, neuropathic pain, or
weakness. Patients experiencing new or worsening PN may require a
delay and a dose reduction or discontinuation of ADCETRIS.
Hematological toxicities: Grade 3 or Grade 4 anemia,
thrombocytopenia, and prolonged (equal to or greater than one week)
Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete
blood counts should be monitored prior to administration of each
dose.
Febrile neutropenia: Febrile neutropenia has been
reported. Patients should be monitored closely for fever and
managed according to best medical practice if febrile neutropenia
develops.
Stevens-Johnson syndrome (SJS): SJS and toxic epidermal
necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes
have been reported. If SJS or TEN occurs, treatment with ADCETRIS
should be discontinued and appropriate medical therapy should be
administered.
Gastrointestinal (GI) Complications: GI complications,
some with fatal outcomes, including intestinal obstruction, ileus,
enterocolitis, neutropenic colitis, erosion, ulcer, perforation and
haemorragh, have been reported. New or worsening GI symptoms should
be promptly evaluated and treated appropriately.
Hepatotoxicity: Elevations in alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) have been reported.
Serious cases of hepatotoxicity, including fatal outcomes, have
also occurred. Liver function should be tested prior to treatment
initiation and routinely monitored in patients receiving ADCETRIS.
Patients experiencing hepatotoxicity may require a delay, dose
modification, or discontinuation of ADCETRIS.
Hyperglycemia: Hyperglycemia has been reported during
trials in patients with an elevated body mass index (BMI) with or
without a history of diabetes mellitus. However, any patient who
experiences an event of hyperglycemia should have their serum
glucose closely monitored. Anti-diabetic treatment should be
administered as appropriate.
Renal and Hepatic Impairment: There is limited experience
in patients with renal and hepatic impairment. Available data
indicate that MMAE clearance might be affected by severe renal
impairment, hepatic impairment, and by low serum albumin
concentrations. The recommended starting dose in patients with
hepatic impairment or severe renal impairment is 1.2 mg/kg
administered as an intravenous infusion over 30 minutes every 3
weeks. Patients with renal or hepatic impairment should be closely
monitored for adverse events.
Sodium content in excipients: This medicinal product
contains a maximum of 2.1 mmol (or 47 mg) of sodium per dose. To be
taken into consideration for patients on a controlled sodium
diet.
INTERACTIONSPatients who are receiving a strong CYP3A4
and P-gp inhibitor, concomitantly with ADCETRIS may have an
increased risk of neutropenia and should be closely monitored.
Co-administration of ADCETRIS with a CYP3A4 inducer did not alter
the plasma exposure of ADCETRIS but it appeared to reduce plasma
concentrations of MMAE metabolites that could be assayed. ADCETRIS
is not expected to alter the exposure to drugs that are metabolized
by CYP3A4 enzymes.
PREGNANCY: Women of childbearing potential should be
using two methods of effective contraception during treatment with
ADCETRIS and until 6 months after treatment. There are no data from
the use of ADCETRIS in pregnant women, although studies in animals
have shown reproductive toxicity. ADCETRIS should not be used
during pregnancy unless the benefit to the mother outweighs the
potential risks to the fetus. If a pregnant woman needs to be
treated, she should be clearly advised on the potential risk to the
fetus.
LACTATION (breast-feeding): There are no data as to
whether ADCETRIS or its metabolites are excreted in human milk,
therefore a risk to the newborn/infant cannot be excluded. With the
potential risk, a decision should be made whether to discontinue
breast-feeding or discontinue/abstain from therapy with
ADCETRIS.
FERTILITY: In nonclinical studies, ADCETRIS treatment has
resulted in testicular toxicity, and may alter male fertility. Men
being treated with this medicine are advised not to father a child
during treatment and for up to 6 months following the last
dose.
ADVERSE REACTIONS
Serious adverse drug reactions were: pneumonia, acute
respiratory distress syndrome, headache, neutropenia,
thrombocytopenia, constipation, diarrhea, vomiting, nausea,
pyrexia, peripheral motor neuropathy, peripheral sensory
neuropathy, hyperglycemia, demyelinating polyneuropathy, tumor
lysis syndrome, and Stevens-Johnson syndrome.
In the clinical studies of ADCETRIS, adverse reactions defined
as very common (≥1/10) were: infection, upper respiratory tract
infection, neutropenia, PN (sensory and motor), cough, dyspneoa,
diarrhea, nausea, vomiting, constipation, abdominal pain, alopecia,
pruritus, myalgia, arthralgia, fatigue, chills, pyrexia,
infusion-related reactions and weight decreased. Adverse reactions
defined as common (≥1/100 to <1/10) were: Sepsis/septic shock,
herpes zoster, pneumonia, herpes simplex, anemia, thrombocytopenia,
hyperglycemia, dizziness, demyelinating polyneuropathy, ALT/AST
increased, rash, and back pain.
ADCETRIS (brentuximab vedotin) U.S. Important Safety
Information
BOXED WARNINGProgressive multifocal
leukoencephalopathy (PML): JC virus infection resulting in PML and
death can occur in patients receiving ADCETRIS.
ContraindicationADCETRIS is contraindicated with
concomitant bleomycin due to pulmonary toxicity (e.g., interstitial
infiltration and/or inflammation).
Warnings and Precautions
- Peripheral neuropathy (PN): ADCETRIS
treatment causes a PN that is predominantly sensory. Cases of motor
PN have also been reported. ADCETRIS-induced PN 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. Patients who experienced a prior
infusion-related reaction should be premedicated for subsequent
infusions. Premedication may include acetaminophen, an
antihistamine, and a corticosteroid.
- 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. First onset
of symptoms occurred at various times from initiation of ADCETRIS
therapy, with some cases occurring within 3 months of initial
exposure. 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.
- Pulmonary toxicityEvents of
noninfectious pulmonary toxicity including pneumonitis,
interstitial lung disease, and acute respiratory distress syndrome,
some with fatal outcomes, have been reported. Monitor patients for
signs and symptoms of pulmonary toxicity, including cough and
dyspnea. In the event of new or worsening pulmonary symptoms, hold
ADCETRIS dosing during evaluation and until symptomatic
improvement.
- 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.
- Gastrointestinal (GI) complications:
Fatal and serious GI complications, including perforation,
hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis,
neutropenic colitis, and ileus have been reported in
ADCETRIS-treated patients. Lymphoma with preexisting GI involvement
may increase the risk of perforation. In the event of new or
worsening GI symptoms, perform a prompt diagnostic evaluation and
treat appropriately.
- Embryo-fetal toxicity: Based on the
mechanism of action and findings in animals, ADCETRIS can cause
fetal harm when administered to a pregnant woman. Females of
reproductive potential should avoid pregnancy during ADCETRIS
treatment and for at least 6 months after the final dose of
ADCETRIS.
Adverse ReactionsIn two uncontrolled single-arm trials of
ADCETRIS as monotherapy in 160 patients with relapsed classical HL
and sALCL, 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.
In a placebo-controlled trial of ADCETRIS in 329 patients with
classical HL at high risk of relapse or progression post-auto-HSCT,
the most common adverse reactions (≥20%) in the ADCETRIS-treatment
arm (167 patients), regardless of causality, were: neutropenia,
peripheral sensory neuropathy, thrombocytopenia, anemia, upper
respiratory tract infection, fatigue, peripheral motor neuropathy,
nausea, cough, and diarrhea.
Drug InteractionsConcomitant 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 PopulationsMMAE exposure and adverse
reactions are increased in patients with moderate or severe hepatic
impairment or severe renal impairment. Avoid use.
Advise females of reproductive potential to avoid pregnancy
during ADCETRIS treatment and for at least 6 months after the final
dose of ADCETRIS.
Advise males with female sexual partners of reproductive
potential to use effective contraception during ADCETRIS treatment
and for at least 6 months after the final dose of ADCETRIS.
Advise patients to report pregnancy immediately and avoid
breastfeeding while receiving ADCETRIS.
For additional Important Safety Information, including Boxed
WARNING, please see the full Prescribing Information for ADCETRIS
at www.seattlegenetics.com or
www.ADCETRIS.com.
Forward Looking Statements for Seattle GeneticsCertain of
the statements made in this press release are forward looking, such
as those, among others, relating to the therapeutic potential,
plans (including timing thereof) for submission of supplemental
regulatory approvals to the FDA and other regulatory authorities in
other countries and the possible market approval of ADCETRIS
(brentuximab vedotin) for uses including CTCL and other
CD30-expressing lymphomas for which ADCETRIS has not received
regulatory approval. 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 that
the safety and/or efficacy results of the ALCANZA trial in
cutaneous T-cell lymphoma and other clinical trials will not be
sufficient to gain marketing approval in the United States or any
other country, that we will be required to amend our submission for
marketing approval or that such submission will be refused or
delayed. In addition, our regulatory plans may change as a result
of consultation with the FDA or other regulatory authorities. More
information about the risks and uncertainties faced by Seattle
Genetics is contained under the caption “Risk Factors” included in
the company’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2016 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161203005007/en/
Takeda:Japanese MediaTsuyoshi Tada, +81 (0)
3-3278-2417tsuyoshi.tada@takeda.comorMedia outside
Japan/EUSara Noonan,
+1-617-551-3683sara.noonan@takeda.comorEuropean MediaKate
Burd, +44 7974 151510kate.burd@takeda.comorSeattle
Genetics:InvestorsPeggy Pinkston,
425-527-4160ppinkston@seagen.comorMediaTricia Larson,
425-527-4180tlarson@seagen.com
Seagen (NASDAQ:SGEN)
Historical Stock Chart
From Mar 2024 to Apr 2024
Seagen (NASDAQ:SGEN)
Historical Stock Chart
From Apr 2023 to Apr 2024