Takeda Submits an Application for a New Indication of Entyvio® (vedolizumab) for the Treatment of Adult Patients with Moderately to Severely Active Crohn’s Disease in Japan

 - Offers Potential New Treatment Option for Patients with Crohn’s Disease - 

Osaka, Japan, July 18, 2018 - Takeda Pharmaceutical Company Limited (TSE: 4502) (“Takeda”) today announced that it has submitted an Application to the Ministry of Health, Labour and Welfare (MHLW) in Japan for the investigational humanized monoclonal antibody Entyvio^® (generic name: vedolizumab, development code: MLN0002) for the treatment of adult patients with moderately to severely active Crohn’s disease (CD) in Japan. On July 2 2018, Takeda received a New Drug Application Approval for Entyvio^® from the MHLW for the treatment of adults with moderate to severely active ulcerative colitis (UC).

The application filing included data from Study CCT-001, a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study investigating the efficacy, safety and pharmacokinetics of vedolizumab induction and maintenance treatment involving 157 Japanese patients with moderately to severely active CD¹ and data from the global GEMINI 2 and 3 randomized, double blind, placebo-controlled pivotal Phase 3 studies involving respectively 1,115 and 416 patients with moderately to severely active CD.^2,3 Results from Study CCT-001 will be presented at a scientific meeting in the near future.

“Crohn’s disease is a chronic, progressive inflammatory disease mainly of the small and large intestine, which typically affects young adults. Symptoms of Crohn’s disease include diarrhea, abdominal pain, fever, weight loss and malnutrition, which can greatly affect the patient’s quality of life,” said Naoyoshi Hirota, head of Takeda Development Center Japan. As the number of patients in Japan suffering from Crohn’s disease has been increasing in recent years, we are pleased that Entyvio^® has taken this important step in becoming a new treatment option, through this submission for Crohn’s disease.”

Entyvio was approved in the European Union and the U.S. in May 2014 for the treatment of adults with moderately to severely UC or CD who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNFα antagonist. Currently, Entyvio has been approved in more than 60 countries worldwide. As of May 2018, global post-marketing exposure to Entyvio totals more than 200,000 patient-years.⁴

About Crohn’s disease
It is estimated that there are currently over 40,000 patients suffering from CD in Japan. CD is one of the most common inflammatory bowel diseases and is characterized by chronic, relapsing, remitting, inflammation that may have skip lesions in the small and large intestine mainly. Common symptoms are diarrhea, abdominal pain, fever, weight loss and malnutrition. Although the exact cause of CD remains unclear, recent research suggests that several factors may play a part, including genetic predisposition, environmental factors, and abnormal immune response to intestinal bacterial antigens.

About Entyvio
Entyvio (vedolizumab) is a prescription medicine that has been approved for adults with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) in more than 60 countries worldwide. In people with UC and CD, there are an increased number of inflammatory white blood cells in the gut. Entyvio is designed to reduce this inflammation by blocking the movement of white blood cells into the inflamed gut tissue. Mucosal addressing cell adhesion molecule 1 (MAdCAM-1) is preferentially expressed on the endothelial lining of blood vessels in the lymphoid tissue of the bowel. The alpha 4 beta 7 integrin is expressed on a subset of circulating white blood cells. Entyvio specifically binds to the alpha4beta7 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 vedolizumab 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.^2,3,5,6

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 1), a placebo-controlled study of vedolizumab induction and maintenance treatment in patients with moderately to severely active CD (GEMINI 2), a placebo-controlled study of vedolizumab induction in patients with moderately to severely active CD (GEMINI 3) and an open-label long-term safety study of vedolizumab in patients with either CD or UC (GEMINI long-term safety).^2,3,5,6

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) 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/

Disclaimer
The drug information contained herein is intended to disclose Takeda's corporate information. Nothing contained herein should be considered a solicitation, promotion or indication for any prescription drug including the ones under development.

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¹ Phase III Study of MLN0002 (300 mg) in Treatment of Crohn's Disease. Available at: https://clinicaltrials.gov/ct2/show/NCT02038920. Updated July 2, 2018. Last accessed July 2018.

² Study of vedolizumab (MLN0002) in patients with moderate to severe Crohn’s disease (GEMINI II). ClinicalTrials.gov Web site. http://www.clinicaltrials.gov/ct2/show/NCT00783692?term=vedolizumab&rank=2. Updated July 21, 2014. Accessed July 2018.

³ Study of vedolizumab in patients with moderate to severe Crohn’s disease (GEMINI III). ClinicalTrials.gov Web site. http://www.clinicaltrials.gov/ct2/show/NCT01224171?term=vedolizumab&rank=4. Updated July 21, 2014. Accessed July 2018.

⁴ Takeda data on file.

⁵ Study of vedolizumab (MLN0002) in patients with moderate to severe ulcerative colitis (GEMINI I). ClinicalTrials.gov Web site. http://www.clinicaltrials.gov/ct2/show/NCT00783718?term=vedolizumab&rank=5. Updated July 18, 2014. Accessed July 2018.

⁶ An open-label study of vedolizumab (MLN0002) in patients with ulcerative colitis and Crohn’s disease (GEMINI LTS). ClinicalTrials.gov Web site. http://www.clinicaltrials.gov/ct2/show/NCT00790933?term=vedolizumab&rank=3. Updated February 20, 2018. Accessed July 2018.