New Real-World Analyses Support Effectiveness and Safety of Entyvio(R) (vedolizumab) for Ulcerative

Data showcased at Digestive Disease Week (DDW) 2017 meeting include presentations of new analyses from the VICTORY consortium

Takeda Pharmaceutical Company Limited [TSE: 4502], ("Takeda") today announced the presentation of eight real-world analyses supporting the effectiveness and safety of Entyvio® (vedolizumab) for the treatment of adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). The data were presented at the 2017 Digestive Disease Week® (DDW) annual scientific meeting in Chicago, Illinois. Two analyses of real-world data from the U.S. VICTORY (Vedolizumab for Health OuTComes in InflammatORY Bowel Diseases) consortium support findings from the pivotal GEMINI clinical trial program demonstrating the efficacy of Entyvio®. 

A cohort analysis (abstract #1853) from the VICTORY consortium concerning predictors of clinical and endoscopic response examined mucosal healing, clinical response and remission and steroid-free response and remission in 180 patients with moderately to severely active UC treated with vedolizumab. Clinical response and remission were based on the physician global assessment score, a 5- or 6-point scoring system used to assess disease severity. In this large, multi-center cohort, a substantial proportion of patients achieved either mucosal healing defined as a Mayo endoscopic subscore of 0 or 1 (77 percent), clinical remission (51 percent) or steroid-free remission (41 percent) by 12 months in routine practice.

"The real-world evidence from the VICTORY consortium supports the data observed in the pivotal GEMINI clinical trial program, further demonstrating the effectiveness of vedolizumab," said Parambir Dulai, M.D., Research Fellow, University of California San Diego, and Lead Investigator of the VICTORY consortium analyses.

An additional analysis (abstract #1785) from the VICTORY consortium examined the rates and predictors of progression to surgery and the proportion of patients with inflammatory bowel disease (IBD) requiring surgery 6 or 12 months after vedolizumab induction in 742 patients (UC=306, CD=436). Investigators observed trends toward a decline in surgical rates over time depending on when vedolizumab was initiated over a two year period. The reasons for these observations are unknown, and further prospective studies are required to characterize these findings.

"Real-world evidence plays an important role in helping healthcare providers evaluate a therapy's effectiveness and safety in routine medical practice against clinical trial results, and the VICTORY consortium provides valuable clinical knowledge for the IBD community," said Professor William Sandborn, M.D., Chief, Division of Gastroenterology, University of California San Diego.

The VICTORY consortium is a collaboration of 10 leading 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. Approximately 900 UC and CD patients are now included in the consortium database, which was started when Entyvio® was launched in the U.S. in 2014.

In addition to real-world analyses, other Takeda-sponsored posters presented at the DDW meeting include evaluations of long-term effectiveness and safety of Entyvio® in patients with UC and CD, as well as post-hoc analyses of GEMINI I and II data. For a full list of poster titles and authors, visit www.ddw.org/attendee-planning/online-planner.

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 integrin is expressed on a subset of circulating white blood cells. Vedolizumab specifically binds to the alpha4beta7 integrin, 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 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 (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

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 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.

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 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.

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, 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.

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, GI acid-related diseases and GI motility disorders. Our GI research & development team is also exploring solutions in celiac disease and nonalcoholic steatohepatitis (NASH), 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.