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22-May-2019

New Exploratory Data from VARSITY, the First Prospective Head-to-Head Ulcerative Colitis Biologic Trial Which Demonstrated Superiority of Vedolizumab to Adalimumab in Clinical Remission at Week 52, Presented at 2019 Digestive Disease Week®

−           Exploratory data showed a greater proportion of patients receiving vedolizumab achieved clinical response at week 14 than adalimumab

−           Additional exploratory data on absence of active histologic disease showed vedolizumab was associated with a greater reduction of microscopic inflammation in the gut compared to adalimumab

−           Results provide additional information to the recent presentation of primary endpoint data from the VARSITY study, which demonstrated superiority of vedolizumab to adalimumab in achieving clinical remission at week 52

 

 

HIGH WYCOMBE, UK, May 19, 2019 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) has announced further results from the Phase 3b prospective head-to-head VARSITY trial, which demonstrated that the gut-selective biologic vedolizumab (Entyvio®) was superior to the anti-tumor necrosis factor-alpha (anti-TNFα) biologic adalimumab (Humira®) in achieving clinical remission* at week 52 in patients with moderately to severely active ulcerative colitis (UC). New exploratory data showed that a greater proportion of patients receiving vedolizumab intravenous (IV) achieved clinical response** at week 14 compared to those treated with adalimumab subcutaneous (SC), 67.1% vs. 45.9% respectively (p< 0.0001). A trend towards separation between the treatment groups was seen as early as week 6, favoring vedolizumab. These results were announced in a Distinguished Abstract Plenary Lecture Presentation at the 2019 Digestive Disease Week® (DDW) annual scientific meeting (May 18-21 in San Diego, CA), one of 18 Takeda sponsored vedolizumab abstracts accepted for presentation.

                                                                                                                            

Additional exploratory data on absence of active histologic disease were also presented at the meeting. Histologic disease activity is an endpoint assessing the degree of microscopic inflammation in the gut. Absence of active histologic disease is achieved when inflammation is less than a pre-defined severity threshold.*** In the VARSITY study, consistent results were seen with vedolizumab treatment across both the Geboes Score (<3.2) and Robarts Histopathology Index (<5), with absence of active histologic disease achieved in 33.4% and 42.3% of patients treated with vedolizumab, respectively, compared with 13.7% and 25.6% of patients treated with adalimumab, respectively (p<0.0001).

 

“Exploratory data from the VARSITY study suggest that more patients experienced early symptomatic response and improvement of microscopic intestinal inflammation with vedolizumab as compared to adalimumab,” said Dr. Bruce E. Sands, primary investigator of the VARSITY study and Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Hospital and the Icahn School of Medicine at Mount Sinai in New York. “In clinical practice there is a need to balance early symptomatic improvement alongside the longer-term treatment goal of helping patients to achieve clinical remission, making these findings important to physicians.”

 

“Patients benefit from clinical trials that advance our understanding of the disease. The VARSITY study, a first-of-its-kind comparison of two biologics in ulcerative colitis, provides valuable information that can help inform treatment decisions, while also increasing our understanding of how these treatments are working at a microscopic level,” said Jeff Bornstein, M.D., Executive Medical Director, Takeda. “Data from the VARSITY study show consistent results for vedolizumab, supporting the use of this treatment as a first-line biologic therapy in ulcerative colitis.”   

 

About VARSITY

VARSITY is a Phase 3b, randomized, prospective, double-blind, double-dummy, multi-center, active-controlled study to evaluate the efficacy and safety of vedolizumab intravenous (IV) compared to adalimumab subcutaneous (SC) at week 52 in patients with moderately to severely active ulcerative colitis. The study randomized 769 patients (vedolizumab n=383 or adalimumab n=386), all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or one tumor necrosis factor-alpha (TNFα)-antagonist other than adalimumab prior to being enrolled. Patients were randomized into one of two treatment groups, vedolizumab IV 300 mg and placebo SC or adalimumab SC 160 mg and placebo IV. Dose escalation was not permitted in either treatment arm during the study.

 

At week 52, 31.3% (n=120/383) of patients receiving vedolizumab IV achieved the primary endpoint of clinical remission* compared to 22.5% (n=87/386) of patients treated with adalimumab SC, with the difference being statistically significant (p=0.0061). In addition, 39.7% of patients treated with vedolizumab achieved the secondary endpoint of mucosal healing± at week 52, compared to 27.7% receiving adalimumab (p=0.0005). A non-statistically significant difference in favor of adalimumab was seen in the percentage of patients using oral corticosteroids at baseline who discontinued corticosteroids and were in clinical remission at week 52. While the study was not powered to compare the safety of the two biologics, patients treated with vedolizumab (62.7%) had a lower rate of overall adverse events than patients treated with adalimumab (69.2%), with a numerically lower rate of infections reported in patients treated with vedolizumab (33.5%) as compared to adalimumab (43.5%). The rate of serious adverse events was also numerically lower in vedolizumab-treated patients than adalimumab (11.0% vs. 13.7% respectively).

 

* Primary endpoint: Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore ˃1 point.

** Exploratory endpoint: Clinical response is defined as a reduction in partial Mayo score of ≥2 points and ≥25% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. Patients with missing clinical response status were considered non-responders.

*** Exploratory endpoint: Absence of active histologic disease is defined as a Geboes Score (<3.2) or Robarts Histopathology Index (<5).

± Secondary endpoint: Mucosal healing is defined as Mayo endoscopic subscore of ≤1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis.

† Secondary endpoint: Corticosteroid-free clinical remission is defined as patients using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission at week 52.

 

About Digestive Disease Week® (DDW)

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 18-21, 2019, at the San Diego Convention Center. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org.

 

About Ulcerative Colitis

Ulcerative colitis (UC) is one of the most common forms of inflammatory bowel disease (IBD). UC is a chronic, relapsing, remitting, inflammatory condition of the gastrointestinal tract that is often progressive in nature, and involves the innermost lining of the large intestine. UC commonly presents with symptoms of abdominal discomfort and loose bowel movements, including blood or pus. 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 the condition.

 

About Entyvio® (vedolizumab)

Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation. It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1). MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract. The alpha4beta7 integrin is expressed on a subset of circulating white blood cells. These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD). By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.

 

Vedolizumab IV is approved for the treatment of adult patients with moderately to severely active UC and CD, 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. Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with more than 260,000 patient years of exposure to date.

 

 

For UK audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO®.

 

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 UK Ltd.

Takeda UK Ltd., located in High Wycombe, is the UK marketing and sales organisation of Takeda Pharmaceutical Company Limited, headquartered in Japan. Takeda Pharmaceutical Company Limited (TSE: 4502, NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience and Rare Diseases. 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.

 

Additional information about Takeda UK Ltd. is available through its corporate website, www.takeda.com/en-gb.

 

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Last Updated: 28-May-2019