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Takeda to Showcase Growing Pipeline and Diversified Portfolio of Oncology Products at Upcoming Scientific Congresses

BusinessWire

– New Data to be Presented at the American Society of Clinical
Oncology (ASCO) Annual Meeting and the Congress of the European
Hematology Association (EHA) Demonstrate Advancements in Medicines
Designed to Address the Unmet Needs of Patients for a Variety of Cancers
–

– Eight Takeda-Sponsored Abstracts Accepted for Presentation at ASCO
2019 and 11 Abstracts Accepted for Presentation at EHA 2019 –

CAMBRIDGE, Mass. & OSAKA, Japan–(BUSINESS WIRE)–Takeda Pharmaceutical Company Limited (TSE:
4502/NYSE:TAK) today announced that the company will present data at
the 55th Annual Meeting of the American Society of Clinical
Oncology (ASCO), May 31-June 4 in Chicago and the 24th
Congress of the European Hematology Association (EHA), June 13-16 in
Amsterdam.

“We look forward to presenting data at ASCO and EHA that illustrate the
continued progress of our portfolio in both clinical research and
real-world settings in solid tumors and blood cancers,” said Phil
Rowlands, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. “These
data demonstrate our continued commitment to the discovery, development
and delivery of medicines for patients with cancers.”

At ASCO, Takeda will present data from both its lung portfolio and
hematology portfolio. Results from a Phase 1/2 first-in-human,
open-label, multicenter study of TAK-788 will be presented orally. The
ongoing study is investigating the antitumor activity and safety of
TAK-788 in patients with locally advanced or metastatic non-small cell
lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor
(EGFR) exon 20 insertion mutations. Takeda also will present three
posters that demonstrate our commitment to furthering the understanding
of patients with anaplastic lymphoma kinase-positive (ALK+) NSCLC
treated with ALUNBRIG® (brigatinib). The Phase 3 PhALLCON
trial – an ongoing efficacy study of ICLUSIG® (ponatinib) in
combination with reduced-intensity chemotherapy in patients with newly
diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia
(Ph+ ALL) – will be featured in a poster presentation. Additional data
from the ECHELON-1 and ECHELON-2 trials evaluating ADCETRIS®
(brentuximab vedotin) as a frontline treatment option in patients with
newly diagnosed Stage III and IV Hodgkin lymphoma and in CD30+
peripheral T-cell lymphoma, respectively, will also be shared in
partnership with Seattle Genetics.

At EHA, additional analyses from the TOURMALINE-MM3 trial, which is
investigating NINLARO™ (ixazomib) as a post-transplant
maintenance therapy in adult patients with multiple myeloma, will be
presented, including quality of life and outcomes in patients who
deepened their responses while on ixazomib maintenance. Furthermore,
preliminary demographics, baseline characteristics and electronic
patient-reported outcomes of patients enrolled in the US MM-6 trial, a
study of multiple myeloma patients who transitioned from treatment with
VELCADE® (bortezomib) to treatment with NINLARO, will be
presented. Real-world findings will also be featured at the meeting,
including results from INSIGHT-MM, a global, prospective,
non-interventional, observational study of presentation, treatment
patterns and outcomes in multiple myeloma by age and geographical
region. ADCETRIS will be featured in encore presentations including
three-year results from the ECHELON-1 trial, which will be presented
during an oral, as well as results from the ECHELON-2 trial.

The eight Takeda-sponsored abstracts accepted for presentation during
ASCO 2019 and 11 abstracts at EHA 2019 include:

ASCO Annual Meeting 2019

Note: All times listed are in Central Daylight Time

TAK-788

ALUNBRIG (brigatinib)

ICLUSIG (ponatinib)

ADCETRIS (brentuximab vedotin)

EHA 24th Congress

Note: All times listed are in Central European Time

Multiple Myeloma / NINLARO (ixazomib)

ADCETRIS (brentuximab vedotin)

For more information, please see ASCO (https://meetings.asco.org/am/program)
and EHA (http://www.eha-2019.org/)
online programs.

About ADCETRIS

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
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 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, and for previously
untreated Stage IV Hodgkin lymphoma in combination with doxorubicin,
vinblastine, and dacarbazine 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 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, (2) for the treatment of adult patients with relapsed or
refractory sALCL, (3) for the treatment of adult patients with
CD30-positive Hodgkin lymphoma at increased risk of relapse or
progression following ASCT, (4) for the treatment of adult patients with
CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior
systemic therapy and (5) for the treatment of adult patients with
previously untreated CD30-positive Stage IV Hodgkin lymphoma in
combination with AVD.

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.

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)

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, and opportunistic
infections such as Pneumocystis jiroveci pneumonia and
oral candidiasis have been reported in patients treated with ADCETRIS.
Carefully monitor patients during treatment for 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, primary
prophylaxis with G-CSF is recommended for all patients beginning with
the first dose.

Stevens-Johnson syndrome (SJS): SJS and toxic epidermal
necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have
been reported. Discontinue treatment with ADCETRIS if SJS or TEN occurs
and administer appropriate medical therapy.

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 experiences an event of hyperglycemia. Administer anti-diabetic
treatment 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.

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.

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 study of ADCETRIS as combination
therapy with AVD in 662 patients with previously untreated advanced HL,
the most common adverse reactions (≥ 10%) were: neutropenia, nausea,
constipation, vomiting, fatigue, peripheral sensory neuropathy,
diarrhoea, pyrexia, alopecia, peripheral motor neuropathy, decreased
weight, abdominal pain, anaemia, stomatitis, febrile neutropenia, bone
pain, insomnia, decreased appetite, cough, headache, arthralgia, back
pain, dyspnoea, myalgia, upper respiratory tract infection, alanine
aminotransferase increased. Serious adverse reactions occurred in 36% of
patients. Serious adverse reactions occurring in ≥ 3% of patients
included febrile neutropenia (17%), pyrexia (6%), and neutropenia (3%).
Adverse events led to treatment discontinuation in 13% of patients.

ADCETRIS (brentuximab vedotin) Important Safety Information (U.S.)

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

Contacts

Takeda Pharmaceutical Company Limited

Japanese Media
Kazumi Kobayashi
kazumi.kobayashi@takeda.com
+81
(0) 3-3278-2095

Media Outside Japan
Sara Noonan
sara.noonan@takeda.com
+1-617-551-3683

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