– Randomized Phase 3 Clinical Trial
of ADCETRIS Combination Met Key Secondary OS Endpoint, Demonstrating a
41% Reduction in Risk of Death vs. Standard of Care in Patients With
Advanced Hodgkin Lymphoma –
CAMBRIDGE, Mass. & OSAKA, Japan & BOTHELL, Wash.-Monday 30 May 2022 [ AETOS Wire ]
(BUSINESS WIRE)
-- Takeda Pharmaceutical Company Limited (TSE:4502) and Seagen Inc.,
(NASDAQ:SGEN) today announced that overall survival (OS) data from the
Phase 3 ECHELON-1 clinical trial of an ADCETRIS® (brentuximab
vedotin) plus chemotherapy combination will be presented in an oral
session at the 59th American Society of Clinical Oncology (ASCO) Annual
Meeting on Friday, June 3, 2022, 1:00-4:00 PM CT, and at the 27th European Hematology Association (EHA) Annual Meeting on Friday, June 10, 2022, 11:30 – 12:45 CEST.
“The longer-term follow-up data from the
ECHELON-1 trial have significant clinical importance, as this trial
represents one of only two frontline randomized studies in advanced
stage Hodgkin lymphoma that shows an overall survival advantage for the
experimental arm,” said Stephen Ansell, M.D., Ph.D., Mayo Clinic, and
ECHELON-1 study investigator. “These results clearly show that the
addition of brentuximab vedotin to chemotherapy improves the long-term
outcome of patients and the combination should be considered a standard
of care.”
Data from the ECHELON-1 trial
demonstrated a statistically significant improvement in OS in adult
patients with previously untreated Stage III or IV classical Hodgkin
lymphoma treated with ADCETRIS plus doxorubicin, vinblastine and
dacarbazine (A+AVD) vs. doxorubicin, bleomycin, vinblastine, and
dacarbazine (ABVD). With approximately six years median follow up (73
months), patients receiving A+AVD had a 41 percent reduction in the risk
of death (hazard ratio [HR] 0.59; 95% confidence interval [CI]: 0.396
to 0.879), with an estimated OS rate (95% CI) of 93.9% (91.6, 95.5) at 6
years. The safety profile of ADCETRIS was consistent with previous
studies, and no new safety signals were observed. Please see Important
Safety Information, including a SPECIAL/BOXED WARNING for progressive
multifocal leukoencephalopathy (PML), for ADCETRIS below.
“Patients with advanced-stage Hodgkin
lymphoma have not benefitted from an improvement in overall survival
outcomes for far too long,” said Chris Arendt, Ph.D., Head of Oncology
Cell Therapy and Therapeutic Area Unit, Research and Development, at
Takeda. “We are extremely proud of the results of the ECHELON-1 trial,
as these findings represent a transformative improvement in care that
can profoundly impact the lives of patients with advanced-stage disease.
We look forward to sharing the data with regulators around the world.”
“These data unequivocally demonstrate
the ability of the ADCETRIS combination regimen to improve upon a
current standard of care, ABVD, for people with Hodgkin lymphoma by
delivering an unsurpassed overall survival benefit,” said Roger Dansey,
M.D., Interim CEO and Chief Medical Officer, Seagen. “We continue to
evaluate the potential of ADCETRIS in different patient populations and
in combination with other approved and investigational medicines.”
ADCETRIS is indicated for the treatment
of adult patients with previously untreated Stage III or IV classical
Hodgkin lymphoma in combination with AVD in the United States and for
the treatment of adult patients with previously untreated CD30-positive
Stage IV Hodgkin lymphoma in combination with AVD in Europe.
First-line brentuximab vedotin
plus chemotherapy to improve overall survival in patients with stage
III/IV classical Hodgkin lymphoma: An updated analysis of ECHELON-1.
(Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia on
Friday, June 3, 2022, 1:00 PM-4:00 PM CT at McCormick Place, Hall A8)
Key findings, which will be presented by Dr. Ansell, include:
-
The trial achieved its key secondary
endpoint with the combination of A+AVD, resulting in a statistically
significant improvement in OS versus the control arm of ABVD as assessed
by an Independent Review Facility (IRF) (HR 0.59; p-value=0.009). This
corresponds to a 41 percent reduction in the risk of death.
-
At a median follow up of 73 months, 39 and 64 OS events occurred in the A+AVD and ABVD arms, respectively.
-
Estimated six-year OS rates (95% CI) were 93.9% (91.6, 95.5) with A+AVD vs. 89.4% (86.6, 91.7) with ABVD.
-
Subgroup analyses supported a consistent benefit for A+AVD vs. ABVD.
-
The six-year PFS estimate (95% CI) was 82.3% (79.1, 85.0) with A+AVD vs. 74.5% (70.8, 77.7) with ABVD.
-
A+AVD resulted in a manageable safety profile consistent with prior reports.
-
Treatment-emergent peripheral
neuropathy continued to resolve or improve in both arms, with 86%
(379/443) and 87% (249/286) of patients in the A+AVD and ABVD arms,
respectively, either completely resolving (72% vs. 79%) or improving
(14% vs. 8%) by last follow up.
-
Fewer patients reported second malignancies in the A+AVD vs. ABVD arm (23 vs. 32).
-
No new safety signals were identified.
About the ECHELON-1 Trial
The ECHELON-1 trial, which compared the
use of ADCETRIS in combination with AVD to ABVD in 1,334 patients with
previously untreated Stage III or IV classical Hodgkin lymphoma, had a
primary endpoint of modified progression-free survival (PFS) per
independent review facility (IRF). A key secondary endpoint was OS,
which was an event-driven, pre-specified, alpha-controlled analysis in
the intention-to-treat population.
About Hodgkin Lymphoma
Lymphoma is a general term for a group
of cancers that originate in the lymphatic system affecting a type of
white blood cell called lymphocytes. There are two major categories of
lymphoma: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Hodgkin
lymphoma is distinguished from other types of lymphoma by the presence
of one characteristic type of cell, known as the Reed-Sternberg cell
present in lymph nodes. Reed-Sternberg cells usually have a special
protein on their surface called CD30, which is a key marker of HL. CD30
is present in approximately 95 percent of all cases of Hodgkin lymphoma.
According to the American Cancer
Society, approximately 8,540 cases of Hodgkin lymphoma will be diagnosed
in the United States during 2022 and more than 900 will die from the
disease. According to the International Agency for Research on Cancer,
as of 2020, over 83,000 people worldwide were diagnosed with Hodgkin
lymphoma and approximately 23,000 people died from this cancer.i
About ADCETRIS® (brentuximab vedotin)
ADCETRIS is an antibody-drug conjugate
(ADC) comprising an anti-CD30 monoclonal antibody attached by a
protease-cleavable linker to a microtubule disrupting agent, monomethyl
auristatin E (MMAE), utilizing Seagen’s 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 six indications in adult patients
with: (1) previously untreated systemic anaplastic large cell lymphoma
(sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL),
including angioimmunoblastic T-cell lymphoma and PTCL not otherwise
specified, in combination with cyclophosphamide, doxorubicin, and
prednisone, (2) previously untreated Stage III or IV classical Hodgkin
lymphoma (cHL), in combination with doxorubicin, vinblastine, and
dacarbazine, (3) cHL at high risk of relapse or progression as
post-autologous hematopoietic stem cell transplantation (auto-HSCT)
consolidation, (4) cHL after failure of auto-HSCT or failure of at least
two prior multi-agent chemotherapy regimens in patients who are not
auto-HSCT candidates, (5) sALCL after failure of at least one prior
multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic
large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF)
who have received prior systemic therapy.
Health Canada granted ADCETRIS approval
with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in
2013, and non-conditional approval for post-autologous stem cell
transplantation (ASCT) consolidation treatment of Hodgkin lymphoma
patients at increased risk of relapse or progression in 2017, adults
with pcALCL or CD30-expressing MF who have had prior systemic therapy in
2018, for previously untreated Stage IV Hodgkin lymphoma in combination
with doxorubicin, vinblastine, and dacarbazine in 2019, and for
previously untreated adult patients with sALCL, peripheral T-cell
lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell
lymphoma (AITL), whose tumors express CD30, in combination with
cyclophosphamide, doxorubicin, prednisone in 2019.
ADCETRIS received conditional marketing
authorization from the European Commission in October 2012. The approved
indications in Europe are: (1) for the treatment of adult patients with
previously untreated CD30-positive Stage IV Hodgkin lymphoma in
combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for
the treatment of adult patients with CD30-positive Hodgkin lymphoma at
increased risk of relapse or progression following ASCT, (3) for the
treatment of adult patients with relapsed or refractory CD30-positive
Hodgkin lymphoma following ASCT, or following at least two prior
therapies when ASCT or multi-agent chemotherapy is not a treatment
option, (4) for the treatment of adult patients with relapsed or
refractory sALCL, and (5) for the treatment of adult patients with
CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior
systemic therapy.
ADCETRIS has received marketing
authorization by regulatory authorities in more than 70 countries for
relapsed or refractory Hodgkin lymphoma and sALCL. See Important Safety
Information below.
ADCETRIS is being evaluated broadly in
more than 70 clinical trials, including a Phase 3 study in first-line
Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line
CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials
in many additional types of CD30-positive malignancies.
Seagen and Takeda are jointly developing
ADCETRIS. Under the terms of the collaboration agreement, Seagen has
U.S. and Canadian commercialization rights and Takeda has rights to
commercialize ADCETRIS in the rest of the world. Seagen 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)
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
CONTRAINDICATIONS
ADCETRIS is contraindicated for patients
with hypersensitivity to brentuximab vedotin and its excipients. In
addition, combined use of ADCETRIS with bleomycin causes pulmonary
toxicity.
SPECIAL WARNINGS & PRECAUTIONS
Progressive multifocal leukoencephalopathy (PML): John
Cunningham virus (JCV) reactivation resulting in progressive multifocal
leukoencephalopathy (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. PML is a rare
demyelinating disease of the central nervous system that results from
reactivation of latent JCV and is often fatal.
Closely monitor patients 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. A negative JCV
PCR does not exclude PML. Additional follow up and evaluation may be
warranted if no alternative diagnosis can be established. Hold dosing
for any suspected case of PML and permanently discontinue ADCETRIS if a
diagnosis of PML is confirmed.
Be alert to PML symptoms that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).
Pancreatitis: Acute
pancreatitis has been observed in patients treated with ADCETRIS. Fatal
outcomes have been reported. Closely monitor patients 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. Hold
ADCETRIS 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, including pneumonitis,
interstitial lung disease, and acute respiratory distress syndrome
(ARDS), 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. Promptly evaluate and treat new
or worsening pulmonary symptoms (e.g., cough, dyspnoea) appropriately.
Consider holding dosing during evaluation and until symptomatic
improvement.
Serious infections and opportunistic infections: Serious
infections such as pneumonia, staphylococcal bacteremia, sepsis/septic
shock (including fatal outcomes), and herpes zoster, cytomegalovirus
(CMV) (reactivation) 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
the emergence of possible serious and opportunistic infections.
Infusion-related reactions (IRR): Immediate
and delayed IRR, as well as anaphylaxis, have been reported with
ADCETRIS. Carefully monitor patients during and after an infusion. If
anaphylaxis occurs, immediately and permanently discontinue
administration of ADCETRIS and administer appropriate medical therapy.
If an IRR occurs, interrupt the infusion and institute appropriate
medical management. 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. Monitor these patients
closely and manage according to best medical practice.
Peripheral neuropathy (PN): ADCETRIS
treatment may cause PN, both sensory and motor. ADCETRIS-induced PN is
typically an effect of cumulative exposure to ADCETRIS and is reversible
in most cases. Monitor patients for symptoms of neuropathy, 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. Monitor complete blood counts prior to administration of each
dose.
Febrile neutropenia: Febrile
neutropenia has been reported with ADCETRIS. Complete blood counts
should be monitored prior to administration of each dose of treatment.
Closely monitor patients for fever and manage according to best medical
practice if febrile neutropenia develops.
When ADCETRIS is administered in
combination with AVD or CHP, primary prophylaxis with G-CSF is
recommended for all patients beginning with the first dose.
Severe cutaneous adverse reactions (SCARs): Cases
of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal
necrolysis (TEN) and drug reaction with eosinophilia and systemic
symptoms (DRESS) have been reported with ADCETRIS. Fatal outcomes have
been reported for SJS and TEN. If SJS, TEN or DRESS occur, 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 haemorrhage, have been reported with ADCETRIS. Promptly
evaluate and treat patients if new or worsening GI symptoms occur.
Hepatotoxicity: Elevations
in alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
have been reported with ADCETRIS. Serious cases of hepatotoxicity,
including fatal outcomes, have also occurred. Pre-existing liver
disease, comorbidities, and concomitant medications may also increase
the risk. Test liver function prior to treatment initiation and
routinely monitor during treatment. 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. Closely
monitor serum glucose for patients who experience an event of
hyperglycemia. Administer anti-diabetic treatment as appropriate.
Infusion site extravasation:
Extravasation during intravenous infusion has occurred. Given the
possibility of extravasation, it is recommended to closely monitor the
infusion site for possible infiltration during drug administration.
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.
CD30+ CTCL: The size of
the treatment effect in CD30 + CTCL subtypes other than mycosis
fungoides (MF) and primary cutaneous anaplastic large cell lymphoma
(pcALCL) is not clear due to lack of high level evidence. In two single
arm phase II studies of ADCETRIS, disease activity has been shown in the
subtypes Sézary syndrome (SS), lymphomatoid papulosis (LyP) and mixed
CTCL histology. These data suggest that efficacy and safety can be
extrapolated to other CTCL CD30+ subtypes. Carefully consider the
benefit-risk per patient and use with caution in other CD30+ CTCL
patient types.
Sodium content in excipients: This
medicinal product contains 13.2 mg sodium per vial, equivalent to 0.7%
of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Traceability: In order
to improve the traceability of biological medicinal products, the name
and the batch number of the administered product should be clearly
recorded.
INTERACTIONS
Patients who are receiving a strong
CYP3A4 and P-gp inhibitor, concomitantly with ADCETRIS may have an
increased risk of neutropenia. If neutropenia develops, refer to dosing
recommendations for neutropenia (see SmPC section 4.2).
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: Advise women
of childbearing potential to use 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. Do not use ADCETRIS
during pregnancy unless the benefit to the mother outweighs the
potential risks 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. Advise men being treated with
ADCETRIS not to father a child during treatment and for up to 6 months
following the last dose.
Effects on ability to drive and use machines: ADCETRIS may have a moderate influence on the ability to drive and use machines.
UNDESIRABLE EFFECTS
Monotherapy: The most
frequent adverse reactions (≥10%) were infections, peripheral sensory
neuropathy, nausea, fatigue, diarrhoea, pyrexia, upper respiratory tract
infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral
motor neuropathy, infusion-related reactions, pruritus, constipation,
dyspnoea, weight decreased, myalgia and abdominal pain. Serious adverse
drug reactions occurred in 12% of patients. The frequency of unique
serious adverse drug reactions was ≤1%. Adverse events led to treatment
discontinuation in 24% of patients.
Combination Therapy: In
the studies of ADCETRIS as combination therapy in 662 patients with
previously untreated advanced HL and 223 patients with previously
untreated CD30+ PTCL, the most common adverse reactions (≥ 10%) were:
infections, neutropenia, peripheral sensory neuropathy, nausea,
constipation, vomiting, diarrhoea, fatigue, pyrexia, alopecia, anaemia,
weight decreased, stomatitis, febrile neutropenia, abdominal pain,
decreased appetite, insomnia, bone pain, rash, cough, dyspnoea,
arthralgia, myalgia, back pain, peripheral motor neuropathy, upper
respiratory tract infection, and dizziness. Serious adverse reactions
occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3%
of patients included febrile neutropenia (15%), pyrexia (5%), and
neutropenia (3%). Adverse events led to treatment discontinuation in 10%
of patients.
ADCETRIS (brentuximab vedotin) for injection 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: Fatal
and serious cases of febrile neutropenia have been reported with
ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4
thrombocytopenia or anemia can occur with ADCETRIS.
Administer G-CSF primary prophylaxis
beginning with Cycle 1 for patients who receive ADCETRIS in combination
with chemotherapy for previously untreated Stage III/IV cHL or
previously untreated PTCL.
Monitor complete blood counts prior to
each ADCETRIS dose. Monitor more frequently 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: Fatal
and serious cases 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: Fatal cases of JC
virus infection resulting in PML have been reported in ADCETRIS-treated
patients. First onset of symptoms occurred at various times from
initiation of ADCETRIS, 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 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: Fatal
and serious events of noninfectious pulmonary toxicity, including
pneumonitis, interstitial lung disease, and acute respiratory distress
syndrome, 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: Fatal
and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN
occurs, discontinue ADCETRIS and administer appropriate medical therapy.
-
Gastrointestinal (GI) complications: Fatal
and serious cases of acute pancreatitis have been reported. Other fatal
and serious GI complications include perforation, hemorrhage, erosion,
ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and
ileus. Lymphoma with preexisting GI involvement may increase the risk of
perforation. In the event of new or worsening GI symptoms, including
severe abdominal pain, perform a prompt diagnostic evaluation and treat
appropriately.
-
Hyperglycemia: Serious
cases, such as new-onset hyperglycemia, exacerbation of pre-existing
diabetes mellitus, and ketoacidosis (including fatal outcomes) have been
reported with ADCETRIS. Hyperglycemia occurred more frequently in
patients with high body mass index or diabetes. Monitor serum glucose
and if hyperglycemia develops, administer anti-hyperglycemic medications
as clinically indicated.
-
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% in any study) Adverse Reactions
Peripheral neuropathy, fatigue, nausea,
diarrhea, neutropenia, upper respiratory tract infection, pyrexia,
constipation, vomiting, alopecia, decreased weight, abdominal pain,
anemia, stomatitis, lymphopenia, and mucositis.
Drug Interactions
Concomitant use of strong CYP3A4
inhibitors or inducers 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 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.
Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here.
About Seagen
Seagen is a global biotechnology company
that discovers, develops and commercializes transformative cancer
medicines to make a meaningful difference in people’s lives. Seagen is
headquartered in the Seattle, Washington area, and has locations in
California, Canada, Switzerland and the European Union. For more
information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.
Forward-Looking Statements
Certain statements made in this press
release are forward looking, such as those, among others, relating to
the therapeutic potential of ADCETRIS, its safety, efficacy and
therapeutic uses, plans to present and publish the specified data, and
anticipated and ongoing development activities for ADCETRIS, including
clinical trial activities. 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 without
limitation the level of utilization and adoption of the referenced
treatment regimen by prescribing physicians, competitive conditions
including the availability of alternative treatment regimens, the
availability and extent of reimbursement, the risk of adverse events or
safety signals, the possibility of adverse regulatory actions, and the
potential for delays or setbacks in product development and the
regulatory review process. More information about the risks and
uncertainties faced by Seagen is contained under the caption “Risk
Factors” included in Seagen’s Quarterly Report on Form 10-Q for the
quarter ended March 31, 2022, and Seagen’s subsequent reports, filed
with the Securities and Exchange Commission. Seagen disclaims any
intention or obligation to update or revise any forward-looking
statements, whether as a result of new information, future events or
otherwise except as required by applicable law.
About Takeda Oncology
At Takeda Oncology, we aspire to cure
cancer, with inspiration from patients and innovation from everywhere.
We ensure a tight connection from research to development to
commercialization and rapidly meet the needs of the cancer community,
optimizing our ability to bring transformative medicines to patients.
Our demonstrated leadership in the treatment of hematologic cancers and
solid tumors combined with cutting-edge science through multiple
platforms, partnerships and therapeutic approaches enable us to bring
novel medicines to patients worldwide.
For more information, visit www.takedaoncology.com.
About Takeda
Takeda is a global, values-based,
R&D-driven biopharmaceutical leader headquartered in Japan,
committed to discover and deliver life-transforming treatments, guided
by our commitment to patients, our people and the planet. Takeda focuses
its R&D efforts on four therapeutic areas: Oncology, Rare Genetics
and Hematology, Neuroscience, and Gastroenterology (GI). We also make
targeted R&D investments in Plasma-Derived Therapies and Vaccines.
We are focusing on developing highly innovative medicines that
contribute to making a difference in people’s lives by advancing the
frontier of new treatment options and leveraging our enhanced
collaborative R&D engine and capabilities to create a robust,
modality-diverse pipeline. Our employees are committed to improving
quality of life for patients and to working with our partners in health
care in approximately 80 countries and regions. For more information,
visit https://www.takeda.com.
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results to differ materially from those expressed or implied by the
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and the United States; competitive pressures and developments; changes
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interest and currency exchange rates; claims or concerns regarding the
safety or efficacy of marketed products or product candidates; the
impact of health crises, like the novel coronavirus pandemic, on Takeda
and its customers and suppliers, including foreign governments in
countries in which Takeda operates, or on other facets of its business;
the timing and impact of post-merger integration efforts with acquired
companies; the ability to divest assets that are not core to Takeda’s
operations and the timing of any such divestment(s); and other factors
identified in Takeda’s most recent Annual Report on Form 20-F and
Takeda’s other reports filed with the U.S. Securities and Exchange
Commission, available on Takeda’s website at: https://www.takeda.com/investors/sec-filings/ or at www.sec.gov.
Takeda does not undertake to update any of the forward-looking
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projection of Takeda’s future results.
Medical information
This press release contains information
about products that may not be available in all countries, or may be
available under different trademarks, for different indications, in
different dosages, or in different strengths. Nothing contained herein
should be considered a solicitation, promotion or advertisement for any
prescription drugs including the ones under development.
i https://www.cancer.org/cancer/hodgkin-lymphoma.html
View source version on businesswire.com: https://www.businesswire.com/news/home/20220525005958/en/
Contacts
Takeda:
Japanese Media
Ryoko Matsumoto
ryoko.matsumoto@takeda.com
+81 (0) 3-3278-3414
Media outside Japan
Emy Gruppo
emy.gruppo@takeda.com
(215) 859-2605
Seagen:
Investors
Peggy Pinkston
ppinkston@seagen.com
(425) 527-4160
Media
David Caouette
dcaouette@seagen.com
(310) 430-3476
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