– Data will be Featured in the Plenary
Scientific Session on December 10, 2017 with Simultaneous
Publication in the New England Journal of Medicine –
– Randomized Phase 3 Clinical Trial with
ADCETRIS Met Primary Endpoint, Demonstrating a Statistically
Significant Improvement in Modified Progression-Free Survival –
Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc.
(NASDAQ: SGEN) today announced that data from the Phase 3 ECHELON-1
clinical trial evaluating ADCETRIS (brentuximab vedotin) as part of
a frontline combination chemotherapy regimen in untreated advanced
classical Hodgkin lymphoma will be presented in the Plenary
Scientific Session at the 59th American Society of Hematology (ASH)
annual meeting on Sunday, December 10, 2017. The data were also
simultaneously published online in the New England Journal of
Medicine and will be published in the print edition on January 25,
2017. Topline data were reported in June 2017 demonstrating the
ECHELON-1 trial met its primary endpoint of a statistically
significant improvement in modified progression-free survival
(modified PFS) per Independent Review Facility (IRF) versus the
control arm. ADCETRIS is an antibody-drug conjugate (ADC) directed
to CD30, a defining marker of classical Hodgkin lymphoma. ADCETRIS
is currently not approved as a frontline therapy for Hodgkin
lymphoma.
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“For patients with advanced stage Hodgkin lymphoma,
approximately one in three do not achieve long-term remission after
standard frontline therapy, which is why the results of ECHELON-1
could be important to this group of patients,” said Jesús Gomez
Navarro, M.D., Vice President, Head of Oncology Clinical Research
and Development, Takeda. “The trial demonstrated that combination
treatment with ADCETRIS resulted in a statistically significant
improvement in modified progression-free survival versus the
control arm. For patients treated with ADCETRIS+AVD, there was a 23
percent reduction in the occurrence of an event, defined as
progression, death or need for subsequent anti-cancer therapy for
patients not in a complete response, compared to those who were
treated with ABVD. We are excited about these clinical trial
results and the potential impact ADCETRIS may have in the treatment
of patients with advanced stage Hodgkin lymphoma if approved by
health authorities for frontline use.”
“The standard of care in the treatment of Hodgkin lymphoma has
not changed over the last several decades and there remains an
unmet need for additional regimens in frontline treatment. Current
regimens include bleomycin, which is known to be associated with
unpredictable and potentially fatal pulmonary toxicity,” said
Joseph M. Connors, M.D., FRCPC, Clinical Director, Center for
Lymphoid Cancer at BC Cancer in Vancouver, Canada. “Increasing the
durable response rate with a frontline therapy that also removes
bleomycin from the regimen, represents a major step forward for the
Hodgkin lymphoma community. Reducing the risk of relapse, is an
important concern for patients and their physicians. In the trial,
33 percent fewer patients treated in the ADCETRIS containing
regimen required subsequent salvage chemotherapy or high dose
chemotherapy and transplant compared to the patients treated with
ABVD. Lastly, the safety profile of ADCETRIS+AVD in the trial was
generally consistent with that known for the single-agent
components of the regimen.”
“The ECHELON-1 Phase 3 clinical trial results were selected by
ASH as one of only six abstracts to be featured in the Plenary
Scientific Session, and the data were also published simultaneously
today in the New England Journal of Medicine. This study represents
a bold effort that began more than five years ago to improve upon
the current standard of care regimen that has not significantly
changed in more than four decades. We’d like to thank the many
patients and physicians who participated in this landmark trial,”
said Clay Siegall, Ph.D., President and Chief Executive Officer of
Seattle Genetics. “These data demonstrate statistically superior
activity of an ADCETRIS-containing regimen over ABVD, the current
standard of care, including the primary endpoint of modified PFS
per IRF, and secondary endpoints trended in favor of the
ADCETRIS-containing regimen as well. Importantly, patients treated
with the ADCETRIS-containing regimen required fewer subsequent
therapies after frontline treatment. The results of the ECHELON-1
study supported FDA Breakthrough Therapy Designation for ADCETRIS
in combination with chemotherapy for frontline advanced classical
Hodgkin lymphoma, and we recently submitted a supplemental
Biologics License Application to the FDA. Our goal is to make this
regimen available to patients in the U.S. with advanced Hodgkin
lymphoma in the first half of 2018.”
Brentuximab Vedotin Plus Doxorubicin, Vinblastine,
Dacarbazine (A+AVD) as Frontline Therapy Demonstrates Superior
Modified Progression-Free Survival versus ABVD in Patients with
Previously Untreated Stage III or IV Hodgkin Lymphoma (HL): The
Phase 3 ECHELON-1 Study (Plenary Scientific Session on Sunday,
December 10, 3:40 p.m. ET at the Georgia World Congress
Center, Building C, Level 1, Hall C2 – C3)
Key findings, which will be presented by Dr. Joseph M. Connors
and published in the New England Journal of Medicine, include:
- The trial achieved its primary endpoint
with the combination of ADCETRIS+AVD resulting in a statistically
significant improvement in modified PFS versus the control arm of
ABVD as assessed by an Independent Review Facility (IRF) (HR 0.77;
p-value=0.035). This corresponds to a 23 percent reduction in the
risk of progression, death or need for additional anticancer
therapy.
- Per IRF assessment, the two-year
modified PFS rate for patients in the ADCETRIS+AVD arm was 82.1
percent compared to 77.2 percent in the control arm.
- Per investigator assessment, the
two-year modified PFS rate for patients in the ADCETRIS+AVD arm was
81.0 percent compared to 74.4 percent in the control arm (HR 0.73;
p-value=0.007). This corresponds to a 27 percent reduction in the
risk of progression, death or need for additional anticancer
therapy.
- All secondary endpoints trended in
favor of the ADCETRIS+AVD arm, including interim analysis of
overall survival (OS; HR 0.72; p-value=0.19). Other secondary
endpoints include:
- Complete response (CR) rate at the end
of randomized regimen in the ADCETRIS+AVD arm was 73 percent
compared to 70 percent in the control arm (p-value=0.22).
- Objective response rate (ORR) at the
end of randomized regimen in the ADCETRIS+AVD arm was 86 percent
compared to 83 percent in the control arm (p-value=0.12).
- Deauville score ≤2 after completion of
frontline therapy was 85 percent in the ADCETRIS+AVD arm compared
to 80 percent in the control arm (p-value=0.03).
- Certain pre-specified subgroups of
patients appeared to benefit more with ADCETRIS+AVD versus ABVD
including: patients treated in North America; patients with
involvement of >1 extranodal site; patients with International
Prognostic Score (IPS) 4 – 7; males; patients with Stage IV
disease; and patients aged <60 years.
- In the ADCETRIS+AVD arm, 33 percent
fewer patients received subsequent salvage chemotherapy or
high-dose chemotherapy and transplant.
- The safety profile of ADCETRIS+AVD in
the ECHELON-1 trial was generally consistent with that known for
the single-agent components of the regimen.
- The most common clinically relevant
adverse events of any grade that occurred in at least 15
percent of patients in the ADCETRIS+AVD and ABVD arms were:
neutropenia (58 and 45 percent, respectively), constipation (42 and
37 percent, respectively), vomiting (33 and 28 percent,
respectively), fatigue (both 32 percent), peripheral sensory
neuropathy (29 and 17 percent, respectively), diarrhea (27 and 18
percent, respectively), pyrexia (27 and 22 percent, respectively),
peripheral neuropathy (26 and 13 percent, respectively), abdominal
pain (21 and 10 percent, respectively) and stomatitis (21 and 16
percent, respectively). In both the ADCETRIS+AVD and ABVD arms, the
most common Grade 3 or 4 events were neutropenia, febrile
neutropenia and neutrophil count decrease.
- Febrile neutropenia was reduced through
the use of prophylactic growth factors (G-CSF) in a subset of
patients. In the ADCETRIS+AVD arm of the study, the rate of febrile
neutropenia without the use of G-CSF was 21 percent and with the
use of G-CSF was reduced to 11 percent. G-CSF primary prophylaxis
with ADCETRIS+AVD resulted in overall comparable safety profile to
ABVD, decreasing incidence of febrile neutropenia, neutropenia and
serious adverse events. Primary prophylaxis with G-CSF was
recommended for all patients.
- On the ADCETRIS+AVD arm, peripheral
neuropathy events were observed in 67 percent of patients compared
to 43 percent on the control arm. In the ADCETRIS+AVD arm, the
majority of peripheral neuropathy events were Grade 1 or 2. Grade
≥3 events were reported in 11 percent of patients and Grade 4
events were reported in less than one percent of patients. In the
control arm, Grade ≥3 events were reported in two percent of
patients and there were no Grade 4 events. Two-thirds of the
patients with peripheral neuropathy in the ADCETRIS+AVD arm
reported resolution or improvement at last follow-up.
- Pulmonary toxicity was reported in two
percent of patients in the ADCETRIS+AVD arm versus seven percent of
patients in the ABVD arm; Grade ≥3 events were reported in less
than one percent versus three percent, in the ADCETRIS and control
arms respectively.
- Nine on study deaths occurred in the
ADCETRIS+AVD arm, of which seven were due to neutropenia or
associated complications (all occurred in patients who had not
received primary prophylaxis with G-CSF with the exception of one
patient who entered the trial with pre-existing neutropenia). The
remaining two deaths were due to myocardial infarction. In the
control arm, there were 13 on study deaths, of which 11 were due to
or associated with pulmonary-related toxicity, one was due to
cardiopulmonary failure and one death had unknown cause.
ECHELON-1 Trial Design
- ECHELON-1 is a randomized, open-label,
two-arm, multi-center Phase 3 study designed to compare ADCETRIS
and AVD (Adriamycin, vinblastine and dacarbazine) to ABVD
(Adriamycin, bleomycin, vinblastine and dacarbazine) as frontline
therapy in patients with previously untreated advanced classical
Hodgkin lymphoma.
- The primary endpoint is modified PFS
per IRF. Modified PFS is defined as time to progression, death, or
evidence of non-complete response after completion of frontline
therapy per IRF followed by subsequent anticancer therapy.
- The key secondary endpoint is OS. Other
secondary objectives include assessment of CR rate, ORR, event-free
survival (EFS), disease-free survival (DFS), duration of response
(DOR), rate of Cycle 2 PET negativity, quality of life measures
(EORTC QLQ C-30) and safety profile in the ADCETRIS+AVD versus ABVD
arms.
- The study enrolled 1,334 patients who
had histologically-confirmed diagnosis of Stage III or IV Hodgkin
lymphoma and had not been previously treated with systemic
chemotherapy or radiotherapy. The median age of the patients
enrolled in the study was 35 in the ADCETRIS+AVD arm and 37 in the
ABVD arm.
- Patients received ADCETRIS+AVD or ABVD
on Days 1 and 15 of each 28-day cycle for up to six cycles.
- The multi-center trial was conducted at
218 sites in 21 countries across North America, Europe, South
America, Australia, Asia and Africa.
The U.S. Food and Drug Administration (FDA) granted Breakthrough
Therapy Designation for ADCETRIS in combination with chemotherapy
for the frontline treatment of patients with advanced classical
Hodgkin lymphoma. Seattle Genetics submitted a supplemental
Biologics License Application to the FDA on November 1, 2017.
Takeda has begun to submit data from the ECHELON-1 trial to
regulatory agencies in its territories, starting with the European
Medicines Agency (EMA) on November 29, 2017.
About Classical Hodgkin Lymphoma
Lymphoma 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. Classical
Hodgkin lymphoma 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 expresses CD30.
According to the American Cancer Society, approximately 8,260
cases of Hodgkin lymphoma will be diagnosed in the United States
during 2017 and more than 1,000 will die from the disease.
According to the Lymphoma Coalition, over 62,000 people worldwide
are diagnosed with Hodgkin lymphoma each year and approximately
25,000 people die each year from this cancer.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical
trials, including three Phase 3 studies: the ECHELON-1 trial in
frontline classical Hodgkin lymphoma that supported the recent FDA
Breakthrough Therapy Designation and submission of the supplemental
Biologics License Application (BLA) for use in this setting, the
ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and
the ongoing CHECKMATE 812 trial of ADCETRIS in combination with
Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.
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 injection for intravenous infusion has received FDA
approval for four indications: (1) regular approval for adult
patients with pcALCL or CD30-expressing MF who have received prior
systemic therapy, (2) 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, (3) regular
approval for the treatment of classical Hodgkin lymphoma patients
at high risk of relapse or progression as post-auto-HSCT
consolidation, and (4) 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 in 2013, and
non-conditional approval for post-ASCT consolidation treatment of
Hodgkin lymphoma patients at increased risk of relapse or
progression.
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.
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.
ADCETRIS has received marketing authorization by regulatory
authorities in 69 countries for relapsed or refractory Hodgkin
lymphoma and sALCL. 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.
ADCETRIS (brentuximab vedotin) Important Safety Information
(European Union)
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.
INTERACTIONS
Patients 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 WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
(PML)
JC virus infection resulting in PML and death can occur in
ADCETRIS-treated patients.
Contraindication
ADCETRIS concomitant with bleomycin due to pulmonary toxicity
(e.g., interstitial infiltration and/or inflammation).
Warnings and Precautions
- Peripheral neuropathy
(PN): ADCETRIS causes PN that is predominantly sensory.
Cases of motor PN have also been reported. ADCETRIS-induced PN is
cumulative. Monitor for symptoms such as hypoesthesia,
hyperesthesia, paresthesia, discomfort, a burning sensation,
neuropathic pain, or weakness. Institute dose modifications
accordingly.
- Anaphylaxis and infusion
reactions: Infusion-related reactions (IRR), including
anaphylaxis have occurred with ADCETRIS. Monitor patients during
infusion. If an IRR occurs, interrupt the infusion and institute
appropriate medical management. If anaphylaxis occurs, immediately
and permanently discontinue the infusion and administer appropriate
medical therapy. Premedicate patients with a prior IRR before
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 ADCETRIS dose. 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 ADCETRIS-treated patients. Closely monitor patients
during treatment for 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 use 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 use in patients with moderate or
severe hepatic impairment.
- Hepatotoxicity: Serious cases,
including fatal outcomes, have occurred in ADCETRIS-treated
patients. Cases were consistent with hepatocellular injury,
including elevations of transaminases and/or bilirubin, and
occurred after the first ADCETRIS dose or rechallenge. Preexisting
liver disease, elevated baseline liver enzymes, and concomitant
medications may increase the risk. Monitor liver enzymes and
bilirubin. Patients with new, worsening, or recurrent
hepatotoxicity may require a delay, change in dose, or
discontinuation of ADCETRIS.
- 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. Other possible contributory factors
other than ADCETRIS include prior therapies and underlying disease
that may cause immunosuppression. Consider PML diagnosis in
patients 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
toxicity: Noninfectious pulmonary toxicity events
including pneumonitis, interstitial lung disease, and acute
respiratory distress syndrome, some with fatal outcomes, have been
reported. Monitor patients for signs and symptoms, 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: Acute pancreatitis, including fatal
outcomes, has been reported in ADCETRIS-treated patients. Other
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 animal
studies, ADCETRIS can cause fetal harm. Advise females of
reproductive potential of the potential risk to the fetus, and to
avoid pregnancy during ADCETRIS treatment and for at least 6 months
after the final dose of ADCETRIS.
Most Common (≥20%) Adverse Reactions: peripheral
sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, upper
respiratory tract infection, and pyrexia.
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
Moderate or severe hepatic impairment or severe renal
impairment: MMAE exposure and adverse reactions are increased.
Avoid use.
Advise males with female sexual partners of reproductive
potential to use effective contraception during, and for at least 6
months after the final dose of ADCETRIS treatment.
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.
About Takeda
Takeda 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 Genetics
Seattle Genetics is an innovative biotechnology company
dedicated to improving the lives of people with cancer through
novel antibody-based therapies. 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. Seattle Genetics commercializes ADCETRIS®
(brentuximab vedotin) for the treatment of several types of
CD30-expressing lymphomas. The company is also advancing a robust
pipeline of novel therapies for solid tumors and blood-related
cancers designed to address significant unmet medical needs and
improve treatment outcomes for patients. More information can be
found at www.seattlegenetics.com and follow @SeattleGenetics on
Twitter.
Forward Looking Statements for Seattle Genetics
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS (brentuximab vedotin) and possible benefits
from its use, and anticipated regulatory approval from the FDA and
other regulatory authorities for frontline Hodgkin lymphoma in the
possible time frame and for the possible uses stated above. 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 the possibility that the safety
and/or efficacy results of the ECHELON-1 trial in Hodgkin lymphoma
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 approval for such
submission will be refused or delayed or conditioned or that the
approved uses will be narrower in scope than stated above. 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, 2017 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/20171210005079/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, +41 79 514 9533kate.burd@takeda.comorSeattle
Genetics:InvestorsPeggy Pinkston,
425-527-4160ppinkston@seagen.comorMediaTricia Larson,
425-527-4180tlarson@seagen.com
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