Osaka, Japan, August 22, 2017 - Takeda Pharmaceutical Company Limited (TSE: 4502) (“Takeda”) announced today that it has submitted a New Drug Application (“NDA”) to the Ministry of Health, Labour and Welfare in Japan for the investigational humanized monoclonal antibody vedolizumab (generic name, development code: MLN0002) for the treatment of adults with moderately to severely active ulcerative colitis (UC).
The NDA filing included data from Study CCT-101, 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 292 Japanese patients with moderate or severe UC. Results from Study CCT-101 will be presented at scientific meeting in the future1. The NDA filing also included data from the international, randomized, double blind, placebo-controlled GEMINI I pivotal Phase 3 study of vedolizumab induction and maintenance treatment involving 895 patients with moderate to severe UC.2
“UC is a chronic, progressive inflammatory disease of the large intestine, which typically affects young adults. The disease has a high impact on their quality of life with symptoms including diarrhea, rectal bleeding, incontinence and abdominal pain,” said Toshiro Heya, head of Takeda Development Center Japan. “Through this submission, we may provide an alternative treatment option to the increasing number of people with UC in Japan.”
“We aim to provide life changing therapeutics for individuals suffering from GI diseases by focusing on underlying disease drivers and leveraging diverse modalities,” said Dr. Asit Parikh, head of Gastroenterology Therapeutic Area.
Vedolizumab was approved in the European Union and the U.S. in May 2014 for the treatment of adults with moderately to severely active UC or Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNFα antagonist. Currently, vedolizumab is approved in more than 60 countries with over 113,000 patient years of exposure to date.3
About ulcerative colitis
Ulcerative colitis is one of the most common forms of inflammatory bowel disease (IBD),3,4 with over 160,000 people with UC in Japan.4 UC is a chronic, relapsing, remitting, inflammatory condition of the gastrointestinal (GI) tract that is often progressive in nature.5 UC involves the innermost lining of the large intestine and often presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus.6,7 The cause of UC 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.8,9
Vedolizumab is a prescription medicine approved for adults with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD) in more than 60 countries worldwide.10,11 In people with UC, there’s an increased number of inflammatory white blood cells entering the mucosal lining of the bowel.12 The presence of these inflammatory cells can lead to the symptoms most commonly seen in people who have UC.13,14,15 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.16 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells. Vedolizumab 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.14
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.17,18,19,20
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).19,20,21
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.21 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.
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.
Takeda Pharmaceutical Company Limited
CCPA Corporate Communications
For media outside Japan
1 Clinicaltrials.gov. Phase III Study of MLN0002 (300 mg) in the Treatment of Ulcerative Colitis. https://clinicaltrials.gov/ct2/show/NCT02039505. Accessed July 2017
2 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 June 19, 2014. Accessed March 16, 2017.
3 Data on file.
3 What is Inflammatory Bowel Disease (IBD)? Centers for Disease Control and Prevention Website. https://www.cdc.gov/ibd/. Accessed February 22, 2017.
4 Baumgart DC, et al. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627-1640.
4 The number is the recipient certificates issued for specific disease treatment of UC in Japan. (Japan Intractable Diseases Information Center home page. http://www.nanbyou.or.jp/entry/62.)
5 Torres J, et al. Ulcerative colitis as a progressive disease: the forgotten evidence. Inflamm Bowel Dis. 2012;18: 1356-1363.
6 The facts about inflammatory bowel disease. Crohn’s and Colitis Foundation. http://www.crohnscolitisfoundation.org/assets/pdfs/ibdfactbook.pdf. Published November 2014. Accessed March 23, 2017.
7 Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation.Gastroenterology. 2004; 126; 1518-1532.
8 Bloom SM, et al. Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe. 2011; 9: 390–403.
9 Kaser A, et al. Genes and environment: How will our concepts on the pathophysiology of IBD develop in the future? Dig Dis. 2010; 28: 395-405.
10 Entyvio Patient Information Leaflet. Takeda Pharmaceuticals. June 2016.
11 Entyvio Summary of Product Characteristics. Takeda Pharmaceuticals. June 2014.
12 Soler D, et al. 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;330:864-875.
13 Baumgart DC, et al. Crohn’s disease. Lancet. 2012; 380;1590-1605.
14 Xavier RJ, et al. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007; 448: 427-434.,
15 The facts about inflammatory bowel disease. Crohn’s and Colitis Foundation. http://www.crohnscolitisfoundation.org/assets/pdfs/ibdfactbook.pdf. Published November 2014. Accessed March 23, 2017.
16 Briskin M, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol. 1997;151:97-110.
17 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 June 19, 2014. Accessed March 16, 2017.
18 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 June 19, 2014. Accessed March 16, 2017.
19 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 June 19, 2014. Accessed March 16, 2017.
20 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 17, 2017. Accessed March 16, 2017.
21 Digestive Health. University of Miami Hospital. http://umiamihospital.com/service-lines/digestive-health. Accessed April 7, 2017.