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New Post-Hoc Analyses Report Early Symptomatic Improvement in Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease Patients Taking Entyvio®(vedolizumab), Particularly in Biologic-Naïve Patients

October 16, 2017

Osaka, Japan, October 16, 2017 – Takeda Pharmaceutical Company Limited [TSE: 4502], (“Takeda”) today announced the presentation of data suggesting early symptomatic improvement in specific symptoms with Entyvio® (vedolizumab) in patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD), particularly in biologic-naïve patients for whom other therapies have not worked well enough. The two analyses from the pivotal GEMINI clinical trial program and additional data regarding the efficacy of Entyvio are being presented at the World Congress of Gastroenterology (WCOG) at ACG2017 in Orlando, Florida.

In two post-hoc analyses of GEMINI data in patients with UC (poster #1273) and CD (poster #1271), symptomatic improvements were evaluated with vedolizumab at weeks 2, 4 and 6, specifically in Mayo Clinic subscores of rectal bleeding and stool frequency in UC, and patient-reported outcome subscores in CD such as abdominal pain and number of liquid or very soft stools. In patients who reported improvements, the greatest differences from placebo were observed in biologic-naïve patients versus the overall treatment group, some as early as week 2.

“The resolution of patient-reported symptoms for both ulcerative colitis and Crohn’s disease examined in these analyses signifies important treatment goals for patients and key indicators for response to treatment for physicians. The results support Entyvio’s value as a therapy for ulcerative colitis and Crohn’s disease with a recognized safety profile and short-and long-term efficacy,” said Brian Feagan M.D., Director of Robarts Clinical Trials at Robarts Research Institute, Western University, London, Ontario, Canada, and lead author of both abstracts. “These post-hoc analyses from the GEMINI clinical trial program underscore the efficacy of Entyvio and its importance as an option for early symptomatic improvement in ulcerative colitis and Crohn’s disease treatment after other treatments fail, particularly in those patients who have not yet received a biologic.”

“The symptoms of inflammatory bowel disease (IBD) have a significant impact on the daily lives of millions of people around the world,” said Karen Lasch, M.D., Medical Head, GI Specialty, U.S. Medical Office, Takeda. “While patients require lifelong disease management, Takeda’s presentation of data evaluating early improvement in symptoms for those receiving Entyvio provides valuable clinical knowledge for the IBD community regarding treatment expectations. Takeda remains committed to contributing to research that helps patients and providers make informed treatment decisions and achieve treatment goals.”

Additional Takeda-sponsored posters presented at the WCOG at ACG2017 include analyses of the efficacy of Entyvio in patients with UC and CD. For a full list of poster titles and authors, visit https://eventscribe.com/2017/wcogacg2017/posteragenda.asp.

About Entyvio® (vedolizumab)
Vedolizumab is a prescription medicine approved for adults with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD). In people with UC and CD, there’s an increased number of inflammatory white blood cells entering the mucosal lining of the bowel. The presence of these inflammatory cells can lead to the symptoms most commonly seen in people who have UC or CD. Vedolizumab is designed to reduce this inflammation by blocking the movement of the white blood cells into the inflamed gut tissue. Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is preferentially expressed on the endothelial lining of blood vessels in the lymphoid tissue of the bowel. The alpha4beta7 (α4β7) integrin is expressed on a subset of circulating white blood cells. Vedolizumab specifically binds to the α4β7 integrin and blocks its interaction with MAdCAM-1, therefore inhibiting the white blood cells from entering the inflamed gut tissue, thus decreasing inflammation.

About the GEMINI Studies
The safety and efficacy of Entyvio® is supported by the results of the GEMINI clinical trial program. These Phase 3 studies involved 2,400 individuals with ulcerative colitis (UC) or Crohn’s disease (CD) who were recruited from nearly 40 countries.

The GEMINI program consists of four studies – a placebo-controlled study of vedolizumab induction and maintenance treatment in patients with moderately to severely active UC (GEMINI I), a placebo-controlled study of vedolizumab induction and maintenance treatment in patients with moderately to severely active CD (GEMINI II), a placebo-controlled study of vedolizumab induction in patients with moderately to severely active CD (GEMINI III) and an open-label long-term safety study of vedolizumab in patients with either CD or UC (GEMINI long-term safety).

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 often 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 (TNFα) 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 (TNFα) antagonist.

Important Safety Information

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.

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 α4β7 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.

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.

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 including Medication Guide for ENTYVIO®.

For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO®.

Takeda’s Commitment to Gastroenterology
More than 70 million people worldwide are impacted by gastrointestinal (GI) diseases, which can be complex, debilitating and life-changing. Takeda is driven to improving the lives of patients with GI diseases through innovative medicines, dedicated patient disease management support and the evolution of the healthcare environment. Takeda is leading in gastroenterology through the delivery of innovative medicines in areas associated with high unmet needs, 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. With more than 25 years of experience in this area, our broad approach to treating many diseases that impact the GI system and our global network of collaborators, Takeda aims to advance how patients manage their disease.

About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited is a global, R&D-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its research efforts on oncology, gastroenterology and central nervous system therapeutic areas. It also has specific development programs in specialty cardiovascular diseases as well as late-stage candidates for vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as its presence in emerging markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.


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Linda Calandra
Takeda Pharmaceuticals U.S.A., Inc.
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