Takeda to Present Data During 60th American Society of Hematology Annual Meeting on Wide Array of Treatment Needs for Blood Cancers

– Results from Phase 3 Studies Including TOURMALINE-MM3 Trial of
NINLARO™ (ixazomib) as Post-
Autologous Stem Cell Transplant
Maintenance Therapy and ECHELON-2 Trial of ADCETRIS
®
(brentuximab vedotin) in Frontline CD30-Positive Peripheral T-Cell
Lymphoma Featured in Oral Sessions –

– Expansive Collection of 18 Abstracts Highlight Takeda’s
Hematology-Oncology Portfolio in Multiple Myeloma, Lymphoma, Chronic
Myeloid Leukemia and Myelodysplastic Syndromes –

CAMBRIDGE, Mass. & OSAKA, Japan–(BUSINESS WIRE)–Takeda Pharmaceutical Company Limited (TSE:
4502
) today announced that it will present a total of 18
company-sponsored abstracts at the 60th American Society of Hematology
(ASH) Annual Meeting taking place in San Diego from December 1 to 4,
2018. Takeda’s presentations will feature new data from clinical studies
across the company’s hematology portfolio. Notably, Takeda will present
data from the Phase 3 TOURMALINE-MM3 and ECHELON-2 clinical trials.

“With the presentation of data from two Phase 3 clinical trials as well
as our pipeline, Takeda continues to grow the body of evidence for new
therapeutic options that improve the way in which we treat blood cancer
patients,” said Christophe Bianchi, M.D., President, Takeda Global
Oncology Business Unit. “Positive data from the TOURMALINE-MM3 trial,
the first and only Phase 3 placebo-controlled study evaluating a
proteasome inhibitor in this setting, showed that using NINLARO as a
post-autologous stem cell transplant maintenance treatment improved
progression-free survival over the control arm, highlighting NINLARO’s
potential use as a maintenance therapy in a patient population where
there are currently limited options. Additionally, the positive data
from the ECHELON-2 trial demonstrated that in patients with previously
untreated CD30-positive peripheral T-cell lymphoma, ADCETRIS in
combination with chemotherapy was superior to the control arm for
progression-free survival and overall survival, representing an
important milestone for ADCETRIS as a potential therapy in this setting
where standard of care has not changed in several decades.”

At this year’s ASH meeting, data from the Phase 3 TOURMALINE-MM3 trial,
evaluating the effect of NINLARO (ixazomib) as a maintenance therapy in
adult patients diagnosed with multiple myeloma who responded to
high-dose therapy (HDT) and autologous stem cell transplant (ASCT), will
be presented for the first time during an oral session on Sunday,
December 2 at 7:30 a.m. PT. The TOURMALINE-MM3 trial achieved its
primary endpoint with NINLARO resulting in a statistically significant
improvement in progression-free survival (PFS) versus placebo as
assessed by an Independent Review Committee (IRC). No new safety signals
were found in TOURMALINE-MM3 and the safety profile of NINLARO in the
maintenance setting is consistent with previously reported results of
single-agent NINLARO use. NINLARO is not currently approved for use as a
single-agent in the post-ASCT maintenance setting.

Data from the Phase 3 ECHELON-2 trial will be presented during an oral
session on Monday, December 3 at 6:15 p.m. PT. The trial demonstrated a
statistically significant improvement in PFS of ADCETRIS (brentuximab
vedotin) in combination with CHP (cyclophosphamide, doxorubicin,
prednisone) versus the control arm, CHOP (cyclophosphamide, doxorubicin,
vincristine, prednisone). Topline data from ECHELON-2 was reported in
October 2018. Results from the trial demonstrated that combination
treatment with ADCETRIS plus CHP was superior to the control arm for PFS
as assessed by an Independent Review Facility (IRF; hazard ratio=0.71;
p-value=0.0110). All key secondary endpoints, including overall
survival, were statistically significant in favor of the ADCETRIS plus
CHP arm, along with the manageable safety profile. ADCETRIS is currently
not approved for the frontline treatment of PTCL.

The breadth and depth of Takeda’s research and development will be
further showcased throughout several presentations focused on multiple
myeloma, lymphoma, chronic myeloid leukemia and myelodysplastic
syndromes (MDS).

18 Takeda Oncology-sponsored abstracts were accepted for presentation
during ASH 2018, including:

Note: All times listed are in Pacific Standard Time

ADCETRIS (brentuximab vedotin)

Multiple Myeloma/NINLARO (ixazomib)

ICLUSIG® (ponatinib)

Pipeline (Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes)

For more information, the ASH program is available here: https://ash.confex.com/ash/2018/webprogram/

About ADCETRIS
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 five indications in adult patients with: (1) previously untreated
Stage III or IV classical Hodgkin lymphoma (cHL), in combination with
chemotherapy, (2) cHL at high risk of relapse or progression as
post-autologous hematopoietic stem cell transplantation (auto-HSCT)
consolidation, (3) 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, (4) sALCL after failure of at least one prior
multi-agent chemotherapy regimen, and (5) 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 transplant (ASCT) consolidation
treatment of Hodgkin lymphoma patients at increased risk of relapse or
progression.

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) 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, and (4) 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.

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
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 occurred with ADCETRIS. Carefully monitor
patients during and after an infusion. If anaphylaxis occurs,
immediately and permanently discontinue administration of ADCETRIS
Appropriate medical therapy should be administered. 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 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. Monitor patients 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. Monitor complete
blood counts prior to administration of each dose.

Febrile neutropenia: Febrile neutropenia has been reported.
Closely monitor patients for fever and manage 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. 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 haemorraghe, have
been reported. 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. Serious cases
of hepatotoxicity, including fatal outcomes, have also occurred. Test
liver function prior to treatment initiation and routinely monitor
patients receiving ADCETRIS for liver elevations. 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
caution in other CD30+ CTCL patient types.

Sodium content in excipients: ADCETRIS contains a maximum of 2.1
mmol (or 47 mg) of sodium per dose. Take this 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: 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
minor influence on the ability to drive and use machines.

UNDESIRABLE EFFECTS
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 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.
Serious adverse drug reactions occurred in 12% of patients. The
frequency of unique serious adverse drug reactions was ≤1%.

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.

Contacts

Takeda Pharmaceutical Company Limited
Japanese Media
Kazumi
Kobayashi, +81 (0) 3-3278-2095
kazumi.kobayashi@takeda.com
or
Media
outside Japan

Victoria von Rinteln, +1-617-444-4391
victoria.vonrinteln@takeda.com

Read full story here

leverton

I have been involved with publishing and marketing for the past 32 years. My passion is helping people share their voice. I am able to do this through two important venues: One, with Area-Info.net where people can share everything from opinions to events to news. It is your choice! What do you want to share? Two, through a new program called America's Real Deal I am involved with to help business owners get their voice heard.I schedule speaking engagements with community groups and business groups to share my passion about the importance of "sharing your voice".Contact me directly at lee@leeeverton.coom for scheduling information.