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Takeda's Vedolizumab Demonstrated Robust Clinical Effectiveness and Safety in Inflammatory Bowel Disease in More Than 50 Real-World Studies

October 17, 2016

In patients with moderate to severely active ulcerative colitis or Crohn’s disease, review of real-world data supports outcomes of vedolizumab clinical trial program

Osaka, Japan, October 17, 2016 –Takeda Pharmaceutical Company Limited [TSE: 4502], (“Takeda”) is presenting data on the real-world effectiveness and safety of vedolizumab in patients with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) during the United European Gastroenterology (UEG) Week in Vienna, Austria, October 16to 19, 2016. Findings indicated notable clinical remission rates, reductions in disease activity scores and improved mucosal healing in more than 5,000 patients with UC and CD receiving treatment with vedolizumab in real-world clinical practice.1

Real-world data are information reported and collected from use of a medication in uncontrolled clinical settings. A systematic review identified 51 reports of real-world studies of vedolizumab. The poster presentation entitled ‘Systematic literature review of real-world effectiveness and safety of vedolizumab in adult UC and CD patients’ included 51 independent cohorts published up to April 2016 describing 5,775 patients treated with vedolizumab, the majority of whom were refractory to prior anti-tumor necrosis factor (TNF) therapies.1 Clinical remission at week 14, measured across a range of definitions, was in the range of 24–55 percent in patients with UC (6 studies) and from 14–38 percent in patients with CD (7 studies). Safety data are consistent with previous vedolizumab clinical trial results in patients with moderately to severely active UC or CD.

“Given that ulcerative colitis and Crohn’s are chronic diseases affecting more than 5 million people worldwide, it is important that we evaluate a treatment’s effectiveness and safety in real-world practice to assess benefit for patients from vedolizumab.2 These data further support the use of vedolizumab and should give physicians confidence in vedolizumab for both biologic naïve and TNF experienced patients,” said Stefan Schrieber, MD, Translational Inflammation Research, Christian Albrechts University, Kiel, Germany.

Additional Data Presented at UEGW
Comparative real-world data with infliximab were also presented at the congress, highlighting key treatment outcomes that are important for patients.3 Findings from a matched, multi-center retrospective cohort study suggested that patients with moderately to severely active UC or CD receiving biologic treatments for the first time treated with vedolizumab were less frequently hospitalized, compared to those receiving infliximab (mean number of IBD-related hospitalizations: 0.11 vedolizumab vs 0.29 infliximab; P=0.048) and may be less likely to discontinue their treatment (HR: 0.86 [95 percent CI: 0.63, 1.16]).

Further findings from a U.S. health records database also showed that patients with UC or CD treated with vedolizumab were less likely to experience an increase in dosage compared to those treated with infliximab during the first 6 months of treatment (4 percent vedolizumab vs. 21.5 percent infliximab; P<0.05).4 This could, in part, reflect the guidance in the US label to increase the dose for patients with CD treated with infliximab who initially respond and then lose response. It is important for treating physicians to consider the impact of dose escalation on patients’ quality of life and health economics in the management of chronic inflammatory conditions such as UC and CD.

“With vedolizumab now approved in more than 50 countries in addition to more than 50,000 patient-years of clinical experience, the real-world data on vedolizumab presented at UEG Week continue to support and build physician confidence in its effectiveness in the management of ulcerative colitis and Crohn’s disease,” said Sharon O'Byrne, MD, Vice President, Global Medical Head, Specialty GI, Takeda Pharmaceuticals. 

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About Ulcerative Colitis and Crohn’s Disease
Ulcerative colitis (UC) and Crohn’s disease (CD) are marked by inflammation in the GI tract. UC impacts the large intestine only, which includes the colon and the rectum. The most common symptoms of UC include abdominal discomfort and blood or pus in diarrhea.5 CD can impact any part of the digestive tract and common symptoms may include abdominal pain, diarrhea, rectal bleeding, weight loss, and fever.6 There is no known cause for UC or CD, although many researchers believe that the interaction between genes, the body’s immune system, and environmental factors play a role.7 The aim of UC and CD treatments is to induce and maintain remission, or achieve extended periods of time when patients do not experience symptoms.5,6

About Entyvio (vedolizumab)
Vedolizumab, developed for the treatment of UC and CD, is a humanized monoclonal antibody that is designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and fibronectin, but not vascular cell adhesion molecule 1 (VCAM-1).8 MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.9 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.8 These cells have been shown to play a role in mediating the inflammatory process in UC and CD. 8,10 By inhibiting alpha4beta7, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.8

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 prepared 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 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 patients is 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, Bronchitis, Upper respiratory tract infection, Influenza, Sinusitis, Headache, Oropharyngeal pain, Cough, Nausea, Rash, Pruritus, Arthralgia, Back pain, Pain in extremities, and Pyrexia.

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
Takeda is a global leader in gastroenterology. With expertise spanning more than 25 years, the company’s dedication to innovation continues to evolve and have a lasting impact. ENTYVIO® (vedolizumab) demonstrates Takeda’s global capabilities and expansion into the specialty care market in gastroenterology and biologics. Designed and developed specifically to target the gastrointestinal (GI) tract, ENTYVIO was launched in 2014 for the treatment of adults with moderate to severe ulcerative colitis and Crohn’s disease. TAKECAB® (vonoprazan fumarate) is Takeda's potassium-competitive acid blocker and was launched in Japan in 2015. Takeda also markets motility agent AMITIZA® (lubiprostone), which originally launched in 2006 for the treatment of chronic idiopathic constipation, and received subsequent approval to treat irritable bowel syndrome with constipation and opioid-induced constipation. Preceding these notable launches, Takeda pioneered gastroenterological breakthroughs in proton pump inhibitors beginning in the 1990’s with lansoprazole. Through specialized and strategic in-house development, external partnerships, in-licensing and acquisitions, Takeda currently has a number of promising early stage GI assets in development, and remains committed to delivering innovative, therapeutic options for patients with gastrointestinal and liver diseases.

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.

Danny Stepto
TEL: +41-44-555-1504
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For Japanese media 
Tsuyoshi Tada 
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1 Bovens SM, et al. Systematic literature review of real-world effectiveness and safety of vedolizumab in adult ulcerative colitis and Crohn’s disease patients. Data presented at: United European Gastroenterology Week 2016 (UEGW): October 15-19; Vienna, Austria.

2 Burisch J and Munkholm P. The epidemiology of inflammatory bowel disease. Scandinavian Journal of Gastroenterology. 2015; 50: 942–951.

3 Raluy-Callado M, et al. Hospitalisations and treatment discontinuation among patients with ulcerative colitis and Crohn’s disease treated with vedolizumab compared with infliximab. Data presented at: United European Gastroenterology Week 2016 (UEGW): October 15-19; Vienna, Austria.

4 Raluy-Callado M, et al. Patterns of dose escalation amongst patients with ulcerative colitis and Crohn’s disease treated with vedolizumab vs. infliximab in the United States (U.S.). Data presented at: United European Gastroenterology Week 2016 (UEGW): October 15-19; Vienna, Austria.

National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Digestive Diseases Information Clearinghouse. Ulcerative colitis. http://digestive.niddk.nih.gov/ddiseases/pubs/colitis/index.aspx. Published September 2014. Accessed January 14, 2015.

6 National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Digestive Diseases Information Clearinghouse. Crohn’s disease. http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/index.aspx. Published September 2014. Accessed January 14, 2015.

7 Crohn’s and Colitis Foundation of America. The facts about inflammatory bowel disease. http://www.ccfa.org/assets/pdfs/ibdfactbook.pdf. Published June, 2011. Accessed January 4, 2013.

8 Soler D, Chapman T, Yang L, Wyant T, Egan R, Fedyk E. The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330(3):864-875. http://jpet.aspetjournals.org/content/330/3/864.full.pdf+html.

9 Briskin M, Winsor-Hines D, Syjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. American Journal of Pathology. 1997;51(1):97.         

10 Gledhill T, Bodger K. New and emerging treatments for ulcerative colitis: a focus on vedolizumab. Biologics: targets and therapy. 2013;7:123-130.