Takeda Receives Approval to Manufacture and Market Entyvio® Subcutaneous Injection in Japan for the Maintenance Treatment of Moderate to Severe Ulcerative Colitis

• Subcutaneous Administration Provides a New Treatment Option for Patients with Ulcerative Colitis Who Have Had an Inadequate Response to Existing Therapies

Osaka, Japan, March 27 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that the Japanese Ministry of Health, Labour and Welfare has approved the use of Entyvio^® Pens for subcutaneous (SC) injection 108 mg / Syringes for SC injection 108 mg (generic name: vedolizumab (Genetical Recombination), development code: MLN0002SC, hereinafter called “Entyvio SC”) as maintenance therapy for moderate to severe ulcerative colitis. Entyvio^®should be used only in patients with inadequate response to conventional treatment.

This approval is based on the MLN0002SC-3027 and MLN0002SC-3030 clinical trials, which are international Phase III trials to evaluate the efficacy and safety of Entyvio SC as a maintenance therapy.

Entyvio SC is intended to provide a dosing option that allows a choice of admistration method that best meets individual needs. SC delivery may reduce the number of personnel, equipment, facilities and time necessary for preparation of the intravenous formulation, which may minimize errors in administration of the drug. It is also intended to provide ease of handling, convenience, and reduce the time required per administration.

Approved indications or effects, dosage and administration

Brand name	Entyvio® Pens for S.C. Injection 108mg / Syringes for S.C. Injection 108mg
Generic name	vedolizumab(Genetical Recombination)
Indications or effects	Maintenance therapy for moderate to severe ulcerative colitis (The drug should be used only in patients with inadequate response to conventional treatment.)
Dosage and Administration	The usual adult dose of vedolizumab (genetical recombination) for subcutaneous injection is 108 mg/dose once every 2 weeks.

“We are delighted that the subcutaneous formulation of Entyvio has been approved. We believe that this approval will provide a wider range of dosing options for ulcerative colitis patients and healthcare professionals and will help meet their diverse needs and improve quality of life,” said Naoyoshi Hirota, General Manager of Takeda Development Center Japan.

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About Ulcerative Colitis

Ulcerative colitis (“UC”)is one of the most common forms of inflammatory bowel disease (IBD), and is estimated to affect about 220,000 people in Japan¹. UC is a chronic, relapsing, remitting, inflammatory condition of the gastrointestinal (GI) tract that is often progressive in nature. UC involves the innermost lining of the large intestine and often presents with symptoms of abdominal discomfort and loose bowel movements, including blood or pus. The cause of UC is not fully understood, but recent research suggests hereditary, genetic, and environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to UC.

About Entyvio^® (vedolizumab)

Vedolizumab is a biologic agent that selectively acts on the gastrointestinal tract. It is currently approved as an intravenous formulation for the treatment of moderate to severe ulcerative colitis and the maintenance of moderate to severe ulcerative colitis and active Crohn’s disease (The drug should be used only in patients with inadequate response to conventional treatment), and as a subcutaneous formulation for the maintenance treatment of moderate to severe ulcerative colitis (The drug should be used only in patients with inadequate response to conventional treatment). It is a humanized monoclonal antibody designed to specifically antagonize the α4β7 integrin, inhibiting the binding of α4β7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1)². MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract³ α4β7 integrin is expressed on a subset of circulating white blood cells2. These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis and Crohn’s disease^2,4 By inhibiting α4β7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.

About Takeda Pharmaceutical Company Limited

Takeda is a global, values-based, R\&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R\&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI). We also make targeted R\&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R\&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. For more information, visit https://www.takeda.com. 

Takeda in Gastroenterology 

We believe that gastrointestinal (GI) and liver diseases are not just life-disrupting conditions, but diseases that can impact a patient’s quality of life. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. With over 30 years of experience in gastroenterology, Takeda has made significant strides in addressing GI patient needs with treatments for inflammatory bowel disease (IBD), acid-related diseases, short bowel syndrome (SBS), and motility disorders. We are making significant strides toward closing the gap on new areas of unmet needs for patients who have celiac disease, eosinophilic esophagitis, alpha-1 antitrypsin-associated liver disease and Crohn’s disease, among others. Together with researchers, patient groups and more, we are working to advance scientific research and clinical medicine in GI. 

Media Contacts:

Japanese Media

Kazuhisa Kaneko

[email protected]

+81-3-3278-3099

Media outside Japan

Mark Dole

[email protected]

+1 (857) 352-6349

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References

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1. Nishiwaki Y et al; National Epidemiological Survey on Prevalence of Ulcerative Colitis and Crohn's Disease: Report of the Results of the Survey, Health Labor Science Research Grants-in-Aid for Scientific Research, 62-76: 2017

2. Soler D, Chapman T, Yang LL, 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. 

3. Briskin M, Winsor-Hines D, Shyjan A, 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.

4. Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its roles in the pathogenesis of IBD. Inflamm Bowel Dis. 2008;14:1298-1312.