− Four-year Analysis Conducted by GHSG Reported ADCETRIS +
ECADD Combination Improved Progression-Free Survival, Showing
Superior Efficacy and Tolerable Safety Profile in Patients with
Newly Diagnosed Stage IIb/III/IV Classical Hodgkin Lymphoma vs
eBEACOPP, a Current Standard of Care in This Setting in
Europe
− The HD21 Study Adds to the Body of Evidence Supporting
ADCETRIS as a Backbone Agent in the Treatment of Specific
Lymphomas
− Results To Be Featured as Oral Presentations at ASCO and
EHA 2024
Takeda (TSE:4502/NYSE:TAK) and Pfizer
(NYSE: PFE) today announced that the German Hodgkin Study Group
(GHSG) will present positive results from the Phase 3 HD21 trial
evaluating ADCETRIS® (brentuximab vedotin) in combination with
chemotherapy as a late-breaking oral presentation at the 60th
American Society of Clinical Oncology (ASCO) Annual Meeting
(LBA7000) and at the 29th European Hematology Association (EHA)
Annual Meeting (S225). The four-year analysis presented by the GHSG
showed superior progression-free survival (PFS) and improved
tolerability for patients compared to a current standard of care
regimen used in Europe in this setting.
The HD21 study is a Phase 3, randomized, multi-country,
prospective, open-label study, sponsored by the GHSG and supported
by Takeda, designed to evaluate ADCETRIS in combination with
etoposide, cyclophosphamide, doxorubicin, dacarbazine and
dexamethasone (BrECADD) in comparison to a standard of care
treatment – escalated doses of bleomycin, etoposide, doxorubicin,
cyclophosphamide, vincristine, procarbazine, prednisone (eBEACOPP)
– in patients with newly diagnosed Stage IIb/III/IV classical
Hodgkin lymphoma. At a preplanned three-year analysis, the study
met its co-primary endpoints, with the ADCETRIS combination regimen
demonstrating significantly improved safety as assessed by
treatment-related morbidity (TRMB) and non-inferior PFS.
The study found that the addition of ADCETRIS to this
chemotherapy regimen improved the risk-to-benefit profile of the
combination treatment, maintaining efficacy with significantly
fewer acute and long-lasting treatment-related toxicities than the
comparator arm.
“We initiated the HD21 trial with the hope of improving outcomes
currently being achieved by a standard of care, as many patients
with newly diagnosed disease often experience a high treatment
burden,” said Peter Borchmann, MD, PhD, University Hospital of
Cologne, Germany, and trial chairman of the HD21 study. “The
presented analysis, in which the ADCETRIS regimen demonstrates
superior progression-free survival, as well as a tolerable safety
profile, reveals the meaningful potential this ADCETRIS + ECADD
regimen has to offer these patients.”
The ASCO presentation provides details of a four-year PFS
analysis of the HD21 study conducted by GHSG. After 48 months,
BrECADD showed superior efficacy to BEACOPP (94.3% PFS for BrECADD
and 90.9% PFS for eBEACOPP; hazard ratio [HR]: 0.66 [95%
CI:88.7-93.1]; p<0.035). As previously reported in the
three-year analysis, treatment with BrECADD was also associated
with a significant reduction in the incidence of TRMB compared with
BEACOPP (n=738; 42% vs 59%; p<0.001), as well as clinically
meaningful reductions in adverse events (AEs). The safety profile
of ADCETRIS in patients receiving BrECADD remained consistent with
other approved ADCETRIS combination regimens, and no new safety
signals were identified.
“In our ongoing effort to improve outcomes for patients with
lymphoma, we’ve partnered with the GHSG on the HD21 study to deepen
our understanding of how ADCETRIS could further benefit patients in
need of new options,” said Awny Farajallah, chief medical officer,
global oncology at Takeda. “We are excited about the impact these
results could have on patients with newly diagnosed Hodgkin
lymphoma, potentially bringing them an additional ADCETRIS-based
combination regimen that may significantly reduce side effects
without compromising on efficacy.”
Takeda will be responsible for submission of potential
regulatory filings based on the HD21 study outside of the U.S. and
Canada. Under the terms of the collaboration agreement, Pfizer has
U.S. and Canadian commercialization rights and Takeda has rights to
commercialize ADCETRIS in the rest of the world.
About the HD21 Trial The HD21 study is a Phase 3,
multi-country, prospective, open-label, randomized, multicenter
trial sponsored by the German Hodgkin Study Group (GHSG) with a
PET-response adapted designed to assess the feasibility, efficacy,
safety and tolerability of BrECADD, a novel, rationally designed,
CD30-intensified frontline regimen for patients with advanced
classical Hodgkin lymphoma.
Enrolled patients with newly diagnosed, Stage IIb with large
mediastinal mass and/or extranodal lesions, Stage III or IV Hodgkin
lymphoma were randomized to receive two cycles of either escalated
BEACOPP or BrECADD, respectively, followed by interim PET staging.
A decision is then made if patients received a further two or four
cycles of escalated BEACOPP or BrECADD.
The HD21 trial aims to evaluate a modified treatment regimen to
minimize side effects, while maintaining similar responses to
treatment. The study has co-primary endpoints: safety is assessed
by treatment-related morbidity (TRMB) (superiority), a novel
endpoint focused on clinically relevant, acute toxicities of
primary chemotherapy, and efficacy is assessed by PFS
(non-inferiority). Secondary endpoints are tumor response (complete
response [CR] rate), overall survival (OS), infertility rate at one
year, second malignancies, frequency of adverse events, therapy
adherence and quality of life.
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 International Agency for Research on Cancer, in
2020, over 83,000 people worldwide were diagnosed with Hodgkin
lymphoma and approximately 23,000 people died from this cancer.
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
Pfizer’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 seven indications:
- Adult patients with previously untreated Stage III/IV classical
Hodgkin lymphoma (cHL) in combination with doxorubicin,
vinblastine, and dacarbazine (2018)
- Pediatric patients 2 years and older with previously untreated
high risk cHL in combination with doxorubicin, vincristine,
etoposide, prednisone and cyclophosphamide (2022)
- Adult patients with cHL at high risk of relapse or progression
as post-autologous hematopoietic stem cell transplantation
(auto-HSCT) consolidation (2015)
- Adult patients with cHL after failure of auto-HSCT or after
failure of at least two prior multi-agent chemotherapy regimens in
patients who are not auto-HSCT candidates (2011)
- Adult patients with 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 (2018)
- Adult patients with sALCL after failure of at least one prior
multi-agent chemotherapy regimen. (2011)
- Adult patients with primary cutaneous anaplastic large cell
lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after
prior systemic therapy (2017)
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, and the specific obligations
of the conditional marketing authorization were fulfilled in May
2022. The approved indications in the European Union are: (1) for
the treatment of adult patients with previously untreated
CD30-positive Stage III & 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, (5) for the treatment of adult
patients with previously untreated sALCL in combination with CHP
and (6) 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.
Pfizer and Takeda fund 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 and 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, dyspnea)
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. A
decision should be made whether to discontinue breast-feeding or to
discontinue/abstain from this therapy, taking into account a
potential risk of breast-feeding for the child and the benefit of
therapy for the woman.
FERTILITY: In non-clinical studies, brentuximab vedotin
treatment has resulted in testicular toxicity, and may alter male
fertility. MMAE has been shown to have anagenic properties.
Therefore, men being treated with this medicine are advised to have
sperm samples frozen and stored before treatment. 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.
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, diarrhea, pyrexia, upper respiratory
tract infection, neutropenia, rash, cough, vomiting, arthralgia,
peripheral motor neuropathy, infusion-related reactions, pruritus,
constipation, dyspnea, 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 (C25003) and 223 patients with previously untreated
CD30+ PTCL, the most common adverse reactions (≥ 10%) were:
infections, neutropenia, peripheral sensory neuropathy, nausea,
constipation, vomiting, diarrhea, fatigue, pyrexia, alopecia,
anemia, weight decreased, stomatitis, febrile neutropenia,
abdominal pain, decreased appetite, insomnia, bone pain, rash,
cough, dyspnea, arthralgia, myalgia, back pain, peripheral motor
neuropathy, upper respiratory tract infection, and dizziness. In
patients receiving ADCETRIS combination therapy, 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 Contraindicated with concomitant
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. Patients experiencing new
or worsening PN may require a delay, change in dose, or
discontinuation of ADCETRIS.
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
adult patients who receive ADCETRIS in combination with
chemotherapy for previously untreated Stage III/IV cHL or
previously untreated PTCL, and pediatric patients who receive
ADCETRIS in combination with chemotherapy for previously untreated
high risk cHL.
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 infections.
Tumor lysis syndrome: Patients with rapidly proliferating
tumor and high tumor burden may be at increased risk. Monitor
closely and take appropriate measures.
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. 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. 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 pre-existing 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 this potential risk, and to use
effective contraception during ADCETRIS treatment and for 2 months
after the last dose of ADCETRIS. Advise male patients with female
partners of reproductive potential to use effective contraception
during ADCETRIS treatment and for 4 months after the last dose of
ADCETRIS.
ADVERSE REACTIONS The most common adverse reactions (≥20%
in any study) are peripheral neuropathy, fatigue, nausea, diarrhea,
neutropenia, upper respiratory tract infection, pyrexia,
constipation, vomiting, alopecia, decreased weight, abdominal pain,
anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and
febrile neutropenia.
DRUG INTERACTIONS Concomitant use of strong CYP3A4
inhibitors has the potential to affect the exposure to monomethyl
auristatin E (MMAE). Closely monitor adverse reactions.
USE IN SPECIAL POPULATIONS
Lactation: Breastfeeding is not recommended during
ADCETRIS treatment.
Please see the full Prescribing Information, including BOXED
WARNING, for ADCETRIS here.
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investment, acquisition, disposal or any other transaction). Any
failure to comply with these restrictions may constitute a
violation of applicable securities laws. The companies in which
Takeda directly and indirectly owns investments are separate
entities. In this press release, “Takeda” is sometimes used for
convenience where references are made to Takeda and its
subsidiaries in general. Likewise, the words “we”, “us” and “our”
are also used to refer to subsidiaries in general or to those who
work for them. These expressions are also used where no useful
purpose is served by identifying the particular company or
companies.
Takeda Forward-Looking Statements This press release and
any materials distributed in connection with this press release may
contain forward-looking statements, beliefs or opinions regarding
Takeda’s future business, future position and results of
operations, including estimates, forecasts, targets and plans for
Takeda. Without limitation, forward-looking statements often
include words such as “targets”, “plans”, “believes”, “hopes”,
“continues”, “expects”, “aims”, “intends”, “ensures”, “will”,
“may”, “should”, “would”, “could” “anticipates”, “estimates”,
“projects” or similar expressions or the negative thereof. These
forward-looking statements are based on assumptions about many
important factors, including the following, which could cause
actual results to differ materially from those expressed or implied
by the forward-looking statements: the economic circumstances
surrounding Takeda’s global business, including general economic
conditions in Japan and the United States; competitive pressures
and developments; changes to applicable laws and regulations,
including global health care reforms; challenges inherent in new
product development, including uncertainty of clinical success and
decisions of regulatory authorities and the timing thereof;
uncertainty of commercial success for new and existing products;
manufacturing difficulties or delays; fluctuations in 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-and-security-reports/
or at www.sec.gov. Takeda does not undertake to update any of the
forward-looking statements contained in this press release or any
other forward-looking statements it may make, except as required by
law or stock exchange rule. Past performance is not an indicator of
future results and the results or statements of Takeda in this
press release may not be indicative of, and are not an estimate,
forecast, guarantee or 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.
Pfizer Disclosure Notice:
The information contained in this release is as of June 1, 2024.
Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or
future events or developments.
This release contains forward-looking information about ADCETRIS
(brentuximab vedotin), including its potential benefits, its
potential in newly diagnosed Stage IIb/III/IV classical Hodgkin
lymphoma, and potential regulatory filings, that involves
substantial risks and uncertainties that could cause actual results
to differ materially from those expressed or implied by such
statements. Risks and uncertainties include, among other things,
uncertainties regarding the commercial success of ADCETRIS; the
uncertainties inherent in research and development, including the
ability to meet anticipated clinical endpoints, commencement and/or
completion dates for our clinical trials, regulatory submission
dates, regulatory approval dates and/or launch dates, as well as
the possibility of unfavorable new clinical data and further
analyses of existing clinical data; the risk that clinical trial
data are subject to differing interpretations and assessments by
regulatory authorities; whether regulatory authorities will be
satisfied with the design of and results from our clinical studies;
whether and when drug applications may be filed in particular
jurisdictions for ADCETRIS with eCADD or as a single agent for any
potential indication; whether and when any applications that may be
pending or filed for ADCETRIS, may be approved by regulatory
authorities, which will depend on myriad factors, including making
a determination as to whether the product's benefits outweigh its
known risks and determination of the product's efficacy and, if
approved, whether ADCETRIS with eCADD or as a single agent will be
commercially successful; decisions by regulatory authorities
impacting labeling, manufacturing processes, safety and/or other
matters that could affect the availability or commercial potential
of ADCETRIS; uncertainties regarding the impact of COVID-19 on
Pfizer’s business, operations and financial results; and
competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2023 and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results”, as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov and www.pfizer.com.
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version on businesswire.com: https://www.businesswire.com/news/home/20240601381068/en/
Takeda Media Contacts: Japanese Media Jun Saito
jun.saito@takeda.com +81 (0) 3-3278-2325
U.S. and International Media Emy Gruppo
emy.gruppo@takeda.com
Pfizer Contacts: Media +1 (212) 733-1226
PfizerMediaRelations@pfizer.com
Investor Relations +1 (212) 733-4848 IR@pfizer.com
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