New Data Presented at European Crohn's and Colitis Organisation (ECCO) Scientific Meeting on Efficacy of Long-Term Vedolizumab Treatment

March 19, 2016

- Analysis reported clinical improvements with up to 152 weeks of vedolizumab treatment seen in patients with moderately to severely active ulcerative colitis

Osaka, Japan, March 19, 2016 – Takeda Pharmaceutical Company Limited [TSE: 4502], (“Takeda”) today announced that the interim findings from the GEMINI Long-Term Safety (LTS) study were presented during the 2016 European Crohn's and Colitis Organisation (ECCO) Annual Scientific Meeting in Amsterdam, The Netherlands. The presented data showed that patients with moderately to severely active ulcerative colitis (UC) reported clinical improvements with approximately three years of treatment with vedolizumab. Findings from a second analysis of GEMINI LTS were also presented and mucosal healing was observed in patients with Crohn’s disease (CD) or UC after long-term treatment with vedolizumab. Mucosal healing is a measure of disease activity in inflammatory bowel disease with greater healing correlated with lower disease activity. Twelve Takeda-sponsored abstracts on vedolizumab, including four oral and eight poster presentations, were accepted to be featured during the ECCO meeting. Vedolizumab was approved as a gut-selective humanized monoclonal antibody in the European Union in 2014, under the trade name Entyvio^®(vedolizumab). Entyvio was also approved in the United States (U.S.) in May 2014. Entyvio is now approved in 48 countries, across three continents.

Interim data from GEMINI Long-Term Safety, an ongoing open-label extension study, where eligible patients received vedolizumab every four weeks, were analyzed for 73 patients with moderately to severely active UC. These patients had completed 152 weeks of cumulative treatment with vedolizumab, having first received vedolizumab either every eight weeks or every four weeks during the GEMINI I maintenance phase after demonstrating an initial response at week 6 to two induction doses. In total, remission was observed in 53 percent and 39 percent of patients for the eight-week and four-week treatment groups, respectively. Higher remission rates (57% and 43%, respectively) were observed in patients who were tumor necrosis factor-alpha (TNF) blocker naïve compared with those who had experienced prior TNF blocker failure (48% and 29%, respectively).

“Interim findings revealed very encouraging levels of remission for patients with ulcerative colitis with approximately three years of treatment and also provided valuable insights about how treatment history may impact treatment success,” said Edward V. Loftus, MD, professor of medicine, Gastroenterology, Mayo Clinic. “Achieving long-term remission is the treatment goal for all patients living with inflammatory bowel diseases, so it is essential that studies like this are conducted to help us understand the long-term efficacy and safety of the treatment options we prescribe.”

A second analysis, which was retrospective, and also based on the GEMINI LTS study population, reports the incidence of mucosal healing and colonic dysplasia in patients with either CD (n=23) or UC (n=39) who were receiving every four-week maintenance dosing of vedolizumab beyond one year. Data from 82 colonoscopies performed after a median of 2.7 years were analyzed (32 CD, 50 UC). Endoscopic healing was defined as a Mayo score of 0 or 1 for UC. The Mayo Score is an assessment of the activity of UC in which 0 indicates the least activity and 1 indicates mild disease (mild erythema, decreased vascular patterns). For CD, marked improvement in endoscopic lesions with persistent ulceration was defined as partial healing, and the absence of ulcers as complete healing. Complete mucosal healing was observed in 44 percent of the CD colonoscopies and partial healing was observed in 38 percent. For the UC colonoscopies, a Mayo Score of 0 was observed for 54 percent, and a Mayo Score of 1 for 20 percent.

“The pivotal Phase 3 GEMINI clinical trial program was the largest ever conducted simultaneously in ulcerative colitis and Crohn’s disease, and continues to yield a great depth of information around the safety and efficacy of vedolizumab,” said Dr. Michael Smyth, global brand medical director, Gastroenterology, Takeda. “Takeda is committed to studying the long-term efficacy and safety of vedolizumab in order to equip the medical community with the best possible tools and data to address the needs of patients who are impacted with these diseases, which are chronic in nature and require long-term treatment.”

Entyvio is the first and only biologic therapy to be approved simultaneously for the treatment of adults with moderately to severely active UC or CD who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF blocker.

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. CD can impact any part of the digestive tract and common symptoms may include abdominal pain, diarrhea, rectal bleeding, weight loss, and fever. 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. 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.

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). 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, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.

INDICATIONS: ENTYVIO^® (vedolizumab)

Adult Ulcerative Colitis (UC)
Adult patients with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids (it says “conventional” therapy in the SmPC):

inducing and maintaining clinical response
inducing and maintaining clinical remission
improving endoscopic appearance of the mucosa
achieving corticosteroid-free remission

Adult Crohn's Disease (CD)
Adult patients with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids (it says “conventional” therapy in the SmPC):

achieving clinical response
achieving clinical remission
achieving corticosteroid-free remission

IMPORTANT SAFETY INFORMATION
Contraindications

ENTYVIO (vedolizumab) is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.

Warnings and Precautions

Infusion-related reactions and hypersensitivity reactions including anaphylaxis have occurred. If anaphylaxis or other serious allergic reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.
Patients treated with ENTYVIO are at increased risk for developing infections. Serious infections have been reported in patients treated with ENTYVIO. ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding ENTYVIO in patients who develop a severe infection while on treatment with ENTYVIO. Exercise caution in patients with a history of recurring severe infections.
Although no cases of PML have been observed in ENTYVIO clinical trials, JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death has occurred in patients treated with another integrin receptor antagonist. A risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms. If PML is suspected, withhold dosing with ENTYVIO and refer to a neurologist; if confirmed, discontinue ENTYVIO dosing permanently.

The risk of malignancy is increased in patients with Ulcerative colitis and Crohn’s disease. (from SmPC)

There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury.
Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines. Patients receiving ENTYVIO may receive non-live vaccines and may receive live vaccines if the benefits outweigh the risks.

Adverse Reactions

USPI version: Most common adverse reactions (incidence greater than or equal to 3% and greater than or equal to 1% higher than placebo): nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.

USPI/SmPC version - includes “Very Common” and “Common” AEs from SmPC: Most common adverse reactions include: nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, Gastroenteritis, Pharyngitis, nasal congestion, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, paraesthesia, hypertension, anal abscess, anal fissure, dyspepsia, constipation, abdominal distension, flatulence, haemorrhoids, eczema, erythema, night sweats, acne, muscle spasms, muscular weakness, oropharyngeal pain, and pain in extremities.

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

For U.S. Audiences, please see the accompanying full Prescribing Information including Medication Guide for ENTYVIO.

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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