Takeda Presents Analyses From Vedolizumab Data in Ulcerative Colitis at 2016 Digestive Disease Week (DDW) Annual Meeting

May 24, 2016

Osaka, Japan, May 24, 2016 – Takeda Pharmaceutical Company Limited [TSE: 4502], (“Takeda”) today announced the oral presentations of two data analyses: one evaluating the optimal position of vedolizumab in the ulcerative colitis (UC) treatment paradigm, and a second separate analysis assessing whether early vedolizumab trough levels were associated with subsequent drug efficacy. Findings were presented during the 2016 Digestive Disease Week (DDW) Annual Meeting in San Diego, California, and were included in a total of 13 Takeda-sponsored vedolizumab or inflammatory bowel disease (IBD)-focused abstracts, including four oral presentations and nine posters.1,2 3,4,5,6,7,8,9,10,11,12,13

“The treatment paradigm for ulcerative colitis is evolving, and further investigation into how to integrate various treatment options may be beneficial for physicians,” said Karen Lasch, M.D., U.S. medical director, Gastroenterology, Takeda. “We believe vedolizumab is an important treatment for patients with ulcerative colitis and these findings help expand our understanding of its use in the clinical setting.”

Vedolizumab is a humanized monoclonal antibody approved in May 2014 in the European Union and the United States under the trade name Entyvio® (vedolizumab). Entyvio is now approved in 49 countries, across five continents. 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 antagonist.14

Vedolizumab oral presentations at DDW 2016 included:           

  • Association of Vedolizumab Drug Concentrations at or Before Week 6 with Remission at Week 14 in Patients with Moderately to Severely Active Ulcerative Colitis from GEMINI 1 (Osterman, Roblin, Glover, et al); presentation #512
    • A post hoc analysis of GEMINI 1 data was completed to assess whether early vedolizumab trough levels were associated with subsequent drug efficacy for the treatment of adults with moderately to severely active UC. In GEMINI 1, patients received either placebo or vedolizumab at weeks 0 and 2. Vedolizumab-treated patients who achieved clinical response at week 6 were randomized to placebo or vedolizumab every 8 or 4 weeks, in this 52 week study. This post hoc analysis focused on the every 8-week dosing group. Clinical remission was determined at week 14, and vedolizumab trough concentrations were summarized by remission status. Percentages of patients in clinical remission were summarized for patients stratified into quartiles based on their vedolizumab trough levels at week 2, 4, or 6.
    • Vedolizumab trough concentrations at week 6 correlated with clinical remission rates at week 14. Patients who achieved clinical remission at week 14 had higher median vedolizumab trough concentrations at weeks 2, 4, and 6 than those not in clinical remission. Further evaluation is needed to help identify if there is an optimal vedolizumab concentration range at an early time point predictive of clinical remission in UC patients.1
  • Determining the Optimal Position for Vedolizumab in the Current Treatment Paradigm for Ulcerative Colitis:  A Markov Model (Scott, Shah, Lasch, Luo, Lewis); presentation #5112
    • A Markov model was constructed to assess where in the current treatment paradigm vedolizumab use would yield the greatest benefit when measured in clinical outcomes and quality adjusted life years (QALYs).
    • This model suggested that incorporating vedolizumab early in the treatment paradigm may result in the greatest potential benefit for individuals with moderate to severe UC who require steroid-sparing therapy.2

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.15 CD can impact any part of the digestive tract and common symptoms may include abdominal pain, diarrhea, rectal bleeding, weight loss, and fever.16 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.17 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.15,16

About Entyvio® (vedolizumab)
Vedolizumab, approved 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).18  MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.19 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.18 These cells have been shown to play a role in mediating the inflammatory process in UC and CD.18,20  By inhibiting alpha4beta7, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.18

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.

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

For EU audiences, please see the Summary of Product Characteristics (SmPC) 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.

Contact:
Danny Stepto
Takeda
TEL: +41-44-555-1504
Danny.Stepto@takeda.com


For Japanese media
Tsuyoshi Tada
Takeda
TEL: +81-3-3278-2417
tsuyoshi.tada@takeda.com

1 Osterman, Roblin, Glover, et al. Association of Vedolizumab Drug Concentrations at or Before Week 6 with Remission at Week 14 in Patients with Moderately to Severely Active Ulcerative Colitis from GEMINI 1. Oral presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #512.

2 Scott, Shah, Lasch, et al. Determining the Optimal Position for Vedolizumab in the Current Treatment Paradigm for Ulcerative Colitis: A Markov Model. Oral presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #511.

3 Martinez, Almario, Dailey, et al. Patient Understanding of the Risks and Benefits of Biologic Therapies in Inflammatory Bowel Disease (IBD): Insights from a Large-Scale Analysis of Social Media Platforms. Oral presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #798.

4 Kosinski, Sorensen, Brill, et al. Project Sonar: Reduction in Cost of Care in an Attributed Cohort of Patients with Crohn’s Disease. Oral presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #824.

5 Lewis, Reinisch, Bressler, et al. Fecal calprotectin reductions in patients with mucosal healing during vedolizumab induction therapy in GEMINI 1. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation # Tu1955.

6 Noman, Ferrante, Bisschops, et al. Mucosal Healing and Dysplasia Surveillance in a Large Referral Center Cohort of Patients with Crohn’s Disease and Ulcerative Colitis Treated with Vedolizumab. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1880.

7 Loftus, Colombel, Previtali, Smyth. Response and Remission Rates with up to 3 Years of Vedolizumab Treatment in Patients with Ulcerative Colitis. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1883.

8 Liang, Manne, Shick, et al. Clinical Characteristics of Patients with Crohn’s Disease or Ulcerative Colitis Treated with Vedolizumab – A Real-World Data Analysis. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1835.

9 Liang, Manne, Shick, et al. Clinical Characteristics of Crohn’s Disease or Ulcerative Colitis Patients who Initiated Vedolizumab or an Anti-TNF-α as First Biologic Therapy. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1834.

10 Liang, Manne, Shick, et al. Clinical Characteristics of Crohn’s Disease and Ulcerative Colitis Patients who Switched from an Anti-TNF-α Agent or Natalizumab to Vedolizumab or an Alternative Anti TNF-α. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1833.

11 Kosinski, Sorensen, Brill, et al. Project Sonar: Validating a Cost Normalization Methodology in a Community-Based Registry. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1094.

12 Vermeire, Feagan, Mody, et al. Response and Remission Rates with up to 3 Years of Vedolizumab Treatment in Patients with Crohn’s Disease. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1879.

13 D’Haens, Colombel, Dubinsky, et al. The Efficacy of Vedolizumab by Disease Activity and Prior Tumor Necrosis Factor A Antagonist Failure in Patients with Ulcerative Colitis or Crohn’s Disease: Post Hoc Analyses from the GEMINI 1 and GEMINI 2 Studies. Poster presentation at the 2016 Digestive Disease Week (DDW) Annual Meeting. Presentation #Mo1882.

14 Entyvio Summary of Product Characteristics. May 2014.

15 National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Digestive Diseases Information Clearinghouse. Ulcerative colitis. http://digestive.niddk.nih.gov/ddiseases/pubs/colitis/index.aspx. Published September 2014. Accessed January 14, 2015.

16 National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Digestive Diseases Information Clearinghouse. Crohn’s disease. http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/index.aspx. Published September 2014. Accessed January 14, 2015.

17 Crohn’s and Colitis Foundation of America. The facts about inflammatory bowel disease. http://www.ccfa.org/assets/pdfs/ibdfactbook.pdf. Published June, 2011. Accessed January 4, 2013.

18 Soler D, Chapman T, Yang L, Wyant T, Egan R, Fedyk E. 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(3):864-875. http://jpet.aspetjournals.org/content/330/3/864.full.pdf+html. Published June 9, 2009. Accessed December 6, 2013.

19 Briskin M, Winsor-Hines D, Syjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. American Journal of Pathology. 1997;51(1):97.         

20 Gledhill T, Bodger K. New and emerging treatments for ulcerative colitis: a focus on vedolizumab. Biologics: targets and therapy. 2013;7:123-130.