Takeda Highlights Favorable Safety Profile of Entyvio® (vedolizumab) Through Comparative Real-World Data Versus TNFalpha-Antagonist Therapy in Ulcerative Colitis and Crohn's Disease

Osaka, Japan (ots/PRNewswire) -

Takeda demonstrates leadership in GI by featuring new U.S. VICTORY
Consortium data among its 24 sponsored Entyvio abstracts presented at
the Digestive Disease Week (DDW) 2018 meeting

Takeda Pharmaceutical Company Limited (TSE: 4502) ("Takeda") today
announced a new analysis of real-world data comparing the safety data
of the gut-selective biologic Entyvio® (vedolizumab) and tumor
necrosis factor-alpha (TNF?)-antagonist therapy. The results showed
numerically lower rates of serious infections (SIs) [6.9% vs 10.1%;
odds ratio (OR) 0.67, 95% confidence interval (CI) 0.41-1.07] and
significantly lower rates of serious adverse events (SAEs) [7.1% vs
13.1%; OR 0.51, 95% CI 0.32-0.81] in patients treated with Entyvio
(n=436) compared to TNF?-antagonist therapy (n=436). This analysis of
the VICTORY (Vedolizumab Health OuTComes in InflammatORY Bowel
Diseases) Consortium evaluated the occurrence of adverse events (AEs)
in patients with ulcerative colitis (UC) and Crohn's disease (CD) who
received vedolizumab compared with TNF?-antagonist therapy and was
presented as an oral presentation at the 2018 Digestive Disease Week®
(DDW) annual scientific meeting held from June 2-5 in Washington,
D.C.

Data from 872 UC and CD patients (n=334 UC, n=538 CD; n=436
Entyvio; 47% male, median age 35 years), from the UC and CD VICTORY
Consortium database, were analyzed to compare the safety of Entyvio
to TNF?-antagonist therapy. Patients receiving Entyvio were matched
(1:1)* to patients on TNF?-antagonist therapy using propensity scores
to control for baseline differences between groups. Among patients on
biologic monotherapy (n=247; n=142 Entyvio), Entyvio-treated patients
were observed to have numerically lower rates of SIs (4.1% vs 10.1%;
OR 0.37, 95% CI 0.13-1.02) and significantly lower rates of SAEs
(4.7% vs 14.5%; OR 0.29, 95% CI 0.12-0.73). Among patients who were
on biologic therapy in combination with both steroids and an
immunomodulator (n=137; n=69 Entyvio), rates of SIs (11.5% vs 13.9%,
OR 0.81, 95% CI 0.31-2.07) and SAEs (14% vs 14%, OR 0.66, 95% CI
0.27-1.65) were similar between Entyvio and TNF?-antagonist treated
patients. Concomitant immunosuppressive use was associated with an
increased risk for both SI and SAE, and rates were similar between
Entyvio and TNF?-antagonist therapy when using concomitant
immunosuppressive therapy.**

"As we add to the extensive body of real-world evidence supporting
the safety profile of Entyvio, it is encouraging to see the lower
rates of serious infections and adverse events as compared to
TNF?-antagonist therapy in this rigorous analysis," said Parambir
Dulai, M.D., Research Fellow, University of California San Diego, and
Lead Investigator of the VICTORY Consortium analyses. "Further
studies will seek to understand the potential impact of gut-selective
treatment versus systemic immunosuppression on clinical safety in the
real world."

Further safety analyses from the GEMINI studies, also presented at
DDW, support the safety profile of Entyvio. Results from a post-hoc
analysis of interim data from the GEMINI long-term safety study
(n=421; UC 190; CD 231) show nearly two-thirds of patients with UC
(64%) and more than half with CD (55%) persisted with Entyvio
treatment for three years, with low rates of discontinuation due to
AEs, and treatment persistence rates higher in patients without
versus with prior TNF?-antagonist failure (UC p=0.18: 69% vs 61%; CD
p<0.01: 68% vs 51%). In addition, the GEMINI open-label extension
(OLE) study showed that patients who were TNF?-antagonist therapy
naïve experienced significantly fewer AEs (94 vs 275 per 100
patient-years) and SAEs (10 vs 18 per 100 patient-years) compared to
TNF?-antagonist -experienced patients. Data from the GEMINI
post-marketing (PM) setting were also analyzed and reported that a
similar number of patients reported AEs in both groups, but
limitations of PM safety reports, including incomplete data, must be
considered when interpreting these results.

"Long-term remission and a well-established safety profile are key
factors when it comes to treating chronic conditions like UC and CD,"
said Karen Lasch, M.D., Medical Head, GI Specialty, U.S. Medical
Office, Takeda. "We are grateful for the work of groups like the
VICTORY Consortium and pleased that results from multiple studies
continue to support the safety and effectiveness of Entyvio."

For a full list of poster titles and authors at this year's DDW
meeting visit, http://www.ddw.org/attendee-planning/online-planner.

*Propensity score matching (1:1) accounting for age, sex, prior
disease-related hospitalization within the previous year, disease
phenotype (stricturing or penetrating complication history for CD,
disease extent for UC), disease severity, prior bowel surgery for CD,
steroid refractoriness or dependence, and prior TNF?-antagonist
failure.

** Rates of SIs and SAEs were compared using logistic regression
analyses between matched patients; SIs were defined as requiring
antibiotics or hospitalization or resulting in discontinuation or
death, and SAEs as SI or non-infectious adverse events resulting in
discontinuation or death.

About Entyvio® (vedolizumab)

Vedolizumab is a gut-selective immunosuppressive biologic. It is a
humanized monoclonal antibody that is designed to specifically
antagonize the alpha4beta7 integrin, inhibiting the binding of
alpha4beta7 integrin to intestinal mucosal addressin cell adhesion
molecule 1 (MAdCAM-1) and fibronectin, but not vascular cell adhesion
molecule 1 (VCAM-1). MAdCAM-1 is preferentially expressed on blood
vessels and lymph nodes of the gastrointestinal tract. The
alpha4beta7 integrin is expressed on a subset of circulating white
blood cells. These cells have been shown to play a role in mediating
the inflammatory process in UC and CD. By inhibiting alpha4beta7
integrin, vedolizumab may limit the ability of certain white blood
cells to infiltrate gut tissues.

About the VICTORY Consortium

The VICTORY (Vedolizumab Health OuTComes in InflammatORY Bowel
Diseases) Consortium is a collaboration currently comprised of 16
leading inflammatory bowel disease (IBD) centers from across the U.S.
and represents the first large, well-characterized cohort of patients
taking Entyvio® in a real-world setting in the U.S. Patients included
in the consortium were identified at each site through electronic
medical record searches, review of clinical records, and/or queries
of infusion center records. More than 1,700 UC and CD patients are
now included in the consortium database, which was started when
Entyvio® was launched in the U.S. in 2014.

About Ulcerative Colitis and Crohn's Disease

Ulcerative colitis (UC) and Crohn's disease (CD) are two of the
most common forms of inflammatory bowel disease (IBD). Both UC and CD
are chronic, relapsing, remitting, inflammatory conditions of the
gastrointestinal (GI) tract that are often progressive in nature. UC
only involves the large intestine as opposed to CD which can affect
any part of the GI tract from mouth to anus. CD can also affect the
entire thickness of the bowel wall, while UC only involves the
innermost lining of the large intestine. UC commonly presents with
symptoms of abdominal discomfort, loose bowel movements, including
blood or pus. CD commonly presents with symptoms of abdominal pain,
diarrhea, and weight loss. The cause of UC or CD is not fully
understood; however, recent research suggests hereditary, genetics,
environmental factors, and/or an abnormal immune response to
microbial antigens in genetically predisposed individuals can lead to
UC or CD.

Therapeutic Indications

Ulcerative colitis

Vedolizumab is indicated for the treatment of adult patients with
moderately to severely active ulcerative colitis who have had an
inadequate response with, lost response to, or were intolerant to
either conventional therapy or a tumor necrosis factor-alpha (TNF?)
antagonist.

Crohn's disease

Vedolizumab is indicated for the treatment of adult patients with
moderately to severely active Crohn's disease who have had an
inadequate response with, lost response to, or were intolerant to
either conventional therapy or a tumor necrosis factor-alpha (TNF?)
antagonist.

Important Safety Information

Contraindications

Hypersensitivity to the active substance or to any of the
excipients.

Special warnings and special precautions for use

Vedolizumab should be administered by a healthcare professional
equipped to manage hypersensitivity reactions, including anaphylaxis,
if they occur. Appropriate monitoring and medical support measures
should be available for immediate use when administering vedolizumab.
Observe all patients during infusion and until the infusion is
complete.

Infusion-related reactions

In clinical studies, infusion-related reactions (IRR) and
hypersensitivity reactions have been reported, with the majority
being mild to moderate in severity. If a severe IRR, anaphylactic
reaction, or other severe reaction occurs, administration of
vedolizumab must be discontinued immediately and appropriate
treatment initiated (e.g., epinephrine and antihistamines). If a mild
to moderate IRR occurs, the infusion rate can be slowed or
interrupted and appropriate treatment initiated (e.g., epinephrine
and antihistamines). Once the mild or moderate IRR subsides, continue
the infusion. Physicians should consider pre-treatment (e.g., with
antihistamine, hydrocortisone and/or paracetamol) prior to the next
infusion for patients with a history of mild to moderate IRR to
vedolizumab, in order to minimize their risks.

Infections

Vedolizumab is a gut-selective integrin antagonist with no
identified systemic immunosuppressive activity. Physicians should be
aware of the potential increased risk of opportunistic infections or
infections for which the gut is a defensive barrier. Vedolizumab
treatment is not to be initiated in patients with active, severe
infections such as tuberculosis, sepsis, cytomegalovirus,
listeriosis, and opportunistic infections until the infections are
controlled, and physicians should consider withholding treatment in
patients who develop a severe infection while on chronic treatment
with vedolizumab. Caution should be exercised when considering the
use of vedolizumab in patients with a controlled chronic severe
infection or a history of recurring severe infections. Patients
should be monitored closely for infections before, during and after
treatment. Before starting treatment with vedolizumab, screening for
tuberculosis may be considered according to local practice. Some
integrin antagonists and some systemic immunosuppressive agents have
been associated with progressive multifocal leukoencephalopathy
(PML), which is a rare and often fatal opportunistic infection caused
by the John Cunningham (JC) virus. By binding to the ?4?7 integrin
expressed on gut-homing lymphocytes, vedolizumab exerts an
immunosuppressive effect on the gut. Although no systemic
immunosuppressive effect was noted in healthy subjects, the effects
on systemic immune system function in patients with inflammatory
bowel disease are not known. No cases of PML were reported in
clinical studies of vedolizumab however, healthcare professionals
should monitor patients on vedolizumab for any new onset or worsening
of neurological signs and symptoms, and consider neurological
referral if they occur. If PML is suspected, treatment with
vedolizumab must be withheld; if confirmed, treatment must be
permanently discontinued. Typical signs and symptoms associated with
PML are diverse, progress over days to weeks, and include progressive
weakness on one side of the body, clumsiness of limbs, disturbance of
vision, and changes in thinking, memory, and orientation leading to
confusion and personality changes. The progression of deficits
usually leads to death or severe disability over weeks or months.

Malignancies

The risk of malignancy is increased in patients with ulcerative
colitis and Crohn's disease. Immunomodulatory medicinal products may
increase the risk of malignancy.

Prior and concurrent use of biological products

No vedolizumab clinical trial data are available for patients
previously treated with natalizumab. Caution should be exercised when
considering the use of vedolizumab in these patients. No clinical
trial data for concomitant use of vedolizumab with biologic
immunosuppressants are available. Therefore, the use of vedolizumab
in such patients is not recommended.

Vaccinations

Prior to initiating treatment with vedolizumab all patients should
be brought up to date with all recommended immunizations. Patients
receiving vedolizumab may receive non-live vaccines (e.g., subunit or
inactivated vaccines) and may receive live vaccines only if the
benefits outweigh the risks.

Adverse reactions include: Nasopharyngitis, Headache, Arthralgia,
Upper respiratory tract infection, Bronchitis, Influenza, Sinusitis,
Cough, Oropharyngeal pain, Nausea, Rash, Pruritus, Back pain, Pain in
extremities, Pyrexia, and Fatigue.

Please consult with your local regulatory agency for approved
labeling in your country.

For U.S. audiences, please see the full Prescribing Information
(https://general.takedapharm.com/ENTYVIOPI) including Medication
Guide (https://general.takedapharm.com/ENTYVIOMG) for ENTYVIO®.

For EU audiences, please see the Summary of Product
Characteristics (SmPC) (http://www.ema.europa.eu/docs/en_GB/document_
library/EPAR_-_Product_Information/human/002782/WC500168528.pdf) for
ENTYVIO®.

Takeda's Commitment to Gastroenterology

Gastrointestinal (GI) diseases can be complex, debilitating and
life-changing. Recognizing this unmet need, Takeda and our
collaboration partners have focused on improving the lives of
patients through the delivery of innovative medicines and dedicated
patient disease support programs for over 25 years. Takeda aspires to
advance how patients manage their disease. Additionally, Takeda is
leading in areas of gastroenterology associated with high unmet need,
such as inflammatory bowel disease, acid-related diseases and
motility disorders. Our GI Research & Development team is also
exploring solutions in celiac disease and liver diseases, as well as
scientific advancements through microbiome therapies.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE: 4502)
(https://www.takeda.com/investors/) is a global, research and
development-driven pharmaceutical company committed to bringing
better health and a brighter future to patients by translating
science into life-changing medicines. Takeda focuses its R&D efforts
on oncology, gastroenterology and neuroscience therapeutic areas plus
vaccines. Takeda conducts R&D both internally and with partners to
stay at the leading edge of innovation. Innovative products,
especially in oncology and gastroenterology, as well as Takeda's
presence in emerging markets, are currently fueling the growth of
Takeda. Around 30,000 Takeda employees are committed to improving
quality of life for patients, working with Takeda's partners in
health care in more than 70 countries.

For more information, visit https://www.takeda.com/newsroom/.

ots Originaltext: Takeda Pharmaceutical Company Limited
Im Internet recherchierbar: http://www.presseportal.de

Contact:
For media outside Japan
Luke Willats
Tel: +41-44-555-1145
Luke.Willats@takeda.com For Japanese media
Kazumi Kobayashi
Tel: +81-3-3278-2095
kazumi.kobayashi@takeda.com

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