Takeda Announces Publication of Study Utilizing State-of-the-Art Modeling to Better Understand Optimal Treatment Positioning for Patients with Ulcerative Colitis

DEERFIELD, Ill., Feb. 6, 2018 /PRNewswire/ -- Takeda Pharmaceuticals, U.S.A., Inc. ("Takeda") today announced the publication of a study utilizing a novel simulation model to predict treatment response in patients with moderately to severely active ulcerative colitis (UC) and help better understand optimal treatment positioning. The study, titled "Assessing the Optimal Position for Vedolizumab in the Treatment of Ulcerative Colitis: A Simulation Model," was published on January 18, 2018 in Inflammatory Bowel Diseases.

Over the last two decades there have been significant advances in the medical management of UC with the development of multiple therapeutic options. As more options become available uncertainty has developed regarding where each should be incorporated into a complex treatment paradigm. There are currently limited data comparing treatment algorithms incorporating sequential therapies. For this study researchers employed state-of-the-art simulation modeling to compare multiple treatment scenarios using the evidence currently available. Scenarios evaluated included the use of Entyvio^® (vedolizumab) as a first-line biologic therapy for a steroid-dependent patient with moderately to severely active UC.

"In the absence of clinical trials comparing treatment algorithms for ulcerative colitis, analyses like this simulation provide tools for helping the clinical community determine the best ways to incorporate specific therapies into practice," said Frank I. Scott, M.D., MSCE, Assistant Professor of Medicine, University of Colorado School of Medicine. "The resulting data help provide valuable insights for healthcare providers evaluating the sequence of therapies for certain patients with ulcerative colitis early in the treatment algorithm."

"Takeda is committed to supporting the GI community by developing innovative disease management tools that aim to help inform patient treatment," said Karen Lasch, M.D., Medical Head, GI Specialty, U.S. Medical Office, Takeda. "The innovative modeling used in this study provides valuable information that can help healthcare professionals make informed treatment decisions when evaluating the increasingly complex treatment paradigm for ulcerative colitis."

Using a Markov model designed to simulate real-world situations based on previous clinical trial data, investigators assessed the optimal positioning for initiating Entyvio therapy based on the case of a 35-year-old male with moderately to severely active UC who was dependent on steroids and had not previously received immunomodulators or biologic therapy. The model compared four treatment scenarios over the course of one year, incorporating Entyvio in different positions within a typical step-up therapy treatment paradigm for patients dependent on steroids: prior to initiating azathioprine, prior to combination therapy with infliximab and azathioprine, prior to combination therapy with adalimumab and azathioprine, and as last-line therapy after combination therapy with adalimumab prior to a colectomy. Primary analyses included simulating 100 trials of 100,000 patients with outcomes assessed in terms of quality-adjusted life years.

The authors concluded that the results of the model simulation support the use of Entyvio as an initial steroid-sparing biologic therapy in steroid-dependent patients with UC. Clinical trials are needed to directly compare sequential treatment algorithms. Complete results from the study can be found on the publication website here: https://academic.oup.com/ibdjournal/article/24/2/286/4816945.

Vedolizumab is approved as a humanized monoclonal antibody and is available in the United States (U.S.) under the trade name Entyvio^® (vedolizumab). It is the first and only biologic therapy to be approved in the U.S. 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 tumor necrosis factor-alpha antagonist.

About Entyvio^® (vedolizumab)

Vedolizumab is a prescription medicine approved for adults with moderate to severe ulcerative colitis (UC) or Crohn's disease (CD). In people with UC and CD, there's an increased number of inflammatory white blood cells entering the mucosal lining of the bowel. The presence of these inflammatory cells can lead to the symptoms most commonly seen in people who have UC or CD. 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. 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.

INDICATIONS: ENTYVIO (vedolizumab)

Adult Ulcerative Colitis (UC)

ENTYVIO (vedolizumab) is indicated in 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 for inducing and maintaining clinical response, inducing and maintaining clinical remission, improving endoscopic appearance of the mucosa, and achieving corticosteroid-free remission.

Adult Crohn's Disease (CD)

ENTYVIO (vedolizumab) is indicated in 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 for achieving clinical response, achieving clinical remission, and achieving corticosteroid‐free remission.

IMPORTANT SAFETY INFORMATION

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

• Infusion-related reactions and hypersensitivity reactions including anaphylaxis have occurred. Allergic reactions including dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have also been observed. 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, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. 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. Consider screening for tuberculosis (TB) according to the local practice.

• 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. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. If PML is suspected, withhold dosing with ENTYVIO and refer to a neurologist; if confirmed, discontinue ENTYVIO dosing permanently.

• 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.

• Most common adverse reactions (incidence ≥3% and ≥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.

Please see the accompanying full Prescribing Information including Medication Guide for ENTYVIO.

More information is available at www.ENTYVIOHCP.com and www.ENTYVIO.com

About Ulcerative Colitis and Crohn's Disease

Ulcerative colitis (UC) and Crohn's disease (CD) are two of the most common forms of inflammatory bowel disease (IBD). Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal (GI) tract that are often progressive in nature. UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus. CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine. UC often presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus. CD commonly presents with symptoms of abdominal pain, diarrhea and weight loss. The cause of UC or CD 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 or CD.

Takeda's Commitment to Gastroenterology

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. 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.

About Takeda Pharmaceuticals U.S.A., Inc.

Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine.

The company has a commercial presence covering around 70 countries, with particular strength in Asia, North America, Europe and fast-growing emerging markets including Latin America, Russia-CIS and China. Areas of R&D focus include central nervous system, cardiovascular and metabolic, gastroenterology, oncology, and vaccines.

Takeda Pharmaceuticals U.S.A., Inc. is located in Deerfield, Ill., and is the U.S. marketing and sales organization of Takeda Pharmaceutical Company Limited.

Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Pharmaceuticals U.S.A., Inc. is available through its website, www.takeda.us.

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. Takeda's growth is being fuelled by products, especially in oncology and gastroenterology, as well as its presence in emerging markets. 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.

SOURCE Takeda Pharmaceuticals, U.S.A., Inc.