Takeda Canada announces positive results for ENTYVIO® (vedolizumab) vs. Humira® (adalimumab) in first IBD study to compare biological agents head-to-head

- ENTYVIO^® superior to Humira^® in achieving clinical remission and mucosal healing at week 52 in patients with moderately to severely active ulcerative colitis

OAKVILLE, ON, March 11, 2019 /CNW/ - Takeda Canada is pleased to announce that ENTYVIO^® (vedolizumab) met the primary and key secondary endpoints in the landmark Phase 3b VARSITY head-to-head study which evaluated the safety and efficacy of gut-selective ENTYVIO^® vs. anti-tumor necrosis factor-alpha (anti-TNFα) biologic Humira^® (adalimumab) in patients with moderately to severely active ulcerative colitis (UC) who had failed conventional therapies.ⁱ The 52-week data were presented as an oral presentation at the 14th Congress of the European Crohn's and Colitis Organization (ECCO) this weekend in Copenhagen, Denmark.ⁱⁱ

The VARSITY trial is the first completed head-to-head superiority study to compare biological agents in inflammatory bowel disease. A total of 769 patients in 37 countries, including Canada were enrolled in the study to evaluate the safety and efficacy of ENTYVIO^® compared to Humira^®.

"VARSITY is important because is it the first IBD study to compare biologics treatments head to head and also because it has the potential to change clinical practice for the future. Achieving mucosal healing and clinical remission are important criteria in treatment selection and these results are a good indicator that for certain patients with moderate to severely active ulcerative colitis vedolizumab can be used as a first line biologic treatment," said Dr. Brian Feagan, a gastroenterologist and Director of Robarts Clinical Trials at the Robarts Research Institute in London, Ontario.

At 52 weeks, patients treated with ENTYVIO^® met the primary and the key secondary endpoint by demonstrating significantly better rates of clinical remission (primary endpoint) and mucosal healing** (secondary endpoint) compared to Humira^®.

Data showed that 31.3% (n=120/383) of patients receiving ENTYVIO^® intravenous (IV) achieved the primary endpoint of clinical remission* compared to 22.5% (n=87/386) of patients treated with Humira^® subcutaneous (SC) at week 52, with the difference being statistically significant (p=0.0061). Furthermore, treatment with ENTYVIO^® was associated with statistically significant higher rates of mucosal healing** at week 52, with 39.7% of patients receiving ENTYVIO^® achieving mucosal healing compared to 27.7% treated with Humira^® (p=0.0005). A non-statistically significant difference in favor of Humira^® was seen in the percentage of patients using oral corticosteroids at baseline who discontinued corticosteroids and were in clinical remission*** at week 52.

Reaction from the Canadian IBD patient community

Mina Mawani, President and CEO, Crohn's and Colitis Canada: "Living with Crohn's disease or ulcerative colitis can be debilitating and there are no cures, but medications can stabilize a patient's condition and allow him or her to lead an active, healthy, and fulfilling life. When it comes to managing chronic diseases, it is important to have the latest information to make informed treatment decisions between the physician and the patient. The more evidence there is to support a treatment, the more comfort that patients and physicians have in achieving the desired outcome."

Jeff Suggitt, CEO, Canadian Digestive Health Foundation: "The results of the VARSITY trial are very exciting for the IBD patient community because it's the first time we have seen a direct comparison between two biologic medicines with distinct modes of action in ulcerative colitis. We look forward to how these results are put into practice for patients."

Gail Attara President and CEO, Gastrointestinal Society (badgut.org): "Ongoing research in this field is a welcome advantage for patients, as it adds to the evidence that informs the standard of care. Each patient has unique needs, and new scientific findings, such as those resulting from the head-to-head VARSITY data, give patients assurance that their physicians have all the latest material they need to provide personalized care. We trust this will result in improved health outcomes for those who have ulcerative colitis."

While the VARSITY study was not powered to compare the safety of the two biologics, patients treated with ENTYVIO^® (62.7%) had a lower rate of overall adverse events over 52 weeks than patients treated with Humira^® (69.2%), with a lower rate of infections reported in patients treated with ENTYVIO^® (33.5%) as compared to Humira^® (43.5%). The rate of serious adverse events was also lower in ENTYVIO^®-treated patients than Humira^® (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.ⁱ

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

*** 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. ⁱ

About ulcerative colitis and Crohn's disease
Ulcerative colitis (UC) and Crohn's disease (CD) are the two main forms of inflammatory bowel disease (IBD).ⁱⁱⁱ Approximately 270,000 Canadians are living with IBD; 135,000 with CD and 120,000 with UC. IBD UC and CD have a typical age of onset in adolescence or early adulthood, though can be diagnosed at any age, including in young children.^iv IBD has been labelled Canada's "national disease" due to Canada having among the highest rates in the world.^v UC causes the tissue of the large intestine (including the colon and rectum) to become inflamed, form sores and bleed easily. Along with symptoms of abdominal pain, cramping, diarrhea, nausea and vomiting, UC can cause severe complications including intestinal bleeding and bowel obstructions. CD may involve inflammation in different parts of the gastrointestinal (GI) tract in different people; however, it most commonly affects the lower part of the small intestine (the ileum) where it joins the beginning of the colon.^vi Sometimes a portion of the bowel needs to be surgically removed to bring patients relief.vii The exact causes of UC and CD are not entirely understood, though they are believed to result from an interaction between genes and the body's immune system, with environmental factors possibly playing a role.^vii

About ENTYVIO^® (vedolizumab)
ENTYVIO^® (vedolizumab) is approved by Health Canada for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, loss of response to, or were intolerant to either conventional therapy or infliximab, a TNFα antagonist.^viii ENTYVIO^® is also 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 immunomodulators or a tumour necrosis factor-alpha (TNFα) antagonist; or have had an inadequate response, intolerance, or demonstrated dependence on corticosteroids.^vii

The recommended dose regimen of ENTYVIO^® is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter.^viii The ENTYVIO^® tolerability profile was demonstrated in the 52-week GEMINI trials, with a low rate of discontinuations due to adverse events: 9% for those on ENTYVIO^® vs.10% for those on placebo.^viii

Canadian researchers played a pivotal role in the treatment's early discovery and development. Researcher Dr. Andrew Lazarovits of London, Ontario, developed a first potential molecule for this type of therapy while working in Boston but passed away in 1999 at age 44.^ix His work was taken up by others, resulting in the development of vedolizumab and eventually international clinical trials financed by Takeda which were led by Dr. Feagan in London, Ontario. The treatment was first used on an ulcerative colitis patient at University Hospital in London^x and Dr. Feagan was the lead author of the publication of the trial results in The New England Journal of Medicine in 2013.^xi

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 Pharmaceutical Company Limited
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, 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.

For more information, visit https://www.takeda.com

About Takeda Canada
Takeda Canada headquarters is currently located in Oakville, Ontario. The Oakville and Toronto offices comprise the Canadian sales and marketing organization of Takeda Pharmaceutical Company Limited. Takeda Canada is delivering better health for Canadians through leading innovations in gastroenterology, oncology, neuroscience, and rare diseases. Additional information about Takeda Canada is available at takeda.com/en-ca.

ENTYVIO^® is a registered trademark of Millennium Pharmaceuticals, Inc. and used under licence by Takeda Canada Inc.

All other trademarks are the property of their respective owner(s).

References

ⁱ ClinicalTrials.gov. An efficacy and safety study of vedolizumab intravenous (IV) compared to adalimumab subcutaneous (SC) in participants with ulcerative colitis; accessed March 2019 at: https://clinicaltrials.gov/ct2/show/NCT02497469.

ⁱⁱ Schreiber S, Peyrin-Biroulet L, Loftus EV Jr, et al. VARSITY: A double-blind, double-dummy, randomised, controlled trial of vedolizumab versus adalimumab in patients with active ulcerative colitis. Presented at the 14th Congress of the Crohn's and Colitis Organisation (ECCO), Copenhagen, Denmark. Oral presentation #OP34 (Saturday March 9, 2019, 09:40-09:50).

ⁱⁱⁱ Crohn's and Colitis Canada, About Crohn's and Colitis; accessed March 2019, at: http://www.crohnsandcolitis.ca/About-Crohn-s-Colitis/What-are-Crohns-and-Colitis 

^iv Crohn's and Colitis Canada, The 2018 Impact of Inflammatory Bowel Disease In Canada Report, Executive Summary; accessed March 2019, at: http://crohnsandcolitis.ca/About-Us/Resources-Publications/Impact-of-IBD-Report

^v Media Planet, Digestive Wellness Supplement, Tackling the burden of ulcerative colitis, March 2015, accessed March 2019, at: http://www.personalhealthnews.ca/prevention-and-treatment/tackling-the-burden-of-ulcerative-colitis

^vi Crohn's and Colitis Canada, About Crohn's and Colitis; accessed March 2019, at: http://www.crohnsandcolitis.ca/About-Crohn-s-Colitis/What-are-Crohns-and-Colitis

^vii Crohn's and Colitis Foundation of America, The Facts about Inflammatory Bowel Disease, page 5, accessed March 2019, at: http://www.ccfa.org/assets/pdfs/updatedibdfactbook.pdf

^viii Takeda Canada Inc., ENTYVIO^® (vedolizumab) Product Monograph, January 28, 2019, p. 3 and 7, and Health Canada Notice of Compliance information. Available at: https://www.takeda.com/siteassets/en-ca/home/what-we-do/our-medicines/product-monographs/entyvio/entivyo-pm-eng-28-jan-2019.pdf

^ix Feagan BG et al, Treatment of Active Crohn's Disease With MLN0002, a Humanized Antibody to the α4β7 Integrin, Clinical Gastroenterology and Hepatology, 2008; 6:12, 1370–1377; accessed March 2019, at: http://www.cghjournal.org/article/S1542-3565%2808%2900617-4/abstract and Sher J, Approval being sought for new treatment for Crohn's and colitis, The London Free Press, Aug. 21, 2013; accessed March 2019, at: http://www.lfpress.com/2013/08/21/approval-being-sought-for-new-treatment-for-crohns-and-colitis

^x Sher J, Approval being sought for new treatment for Crohn's and colitis, The London Free Press, Aug. 21, 2013; accessed March 2019, at: http://www.lfpress.com/2013/08/21/approval-being-sought-for-new-treatment-for-crohns-and-colitis

^xi Feagan BG et al, Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis, N Engl J Med 2013; 369:699-710, August 22, 2013, accessed March 2019, at: http://www.nejm.org/doi/full/10.1056/NEJMoa1215734

SOURCE Takeda Canada Inc.

Media Contact: Natacha Raphael, [email protected], 289-795-5614