Analysis of real-world safety data shows gut-selective ENTYVIO® (vedolizumab) had fewer serious infections and adverse events than those on systemic TNFα-antagonist therapy in ulcerative colitis and Crohn's disease patients

New data from VICTORY Consortium among Takeda's 24 sponsored ENTYVIO^® abstracts presented at Digestive Disease Week 2018 meeting in Washington, D.C.

OAKVILLE, ON, June 5, 2018 /CNW/ - Results of a new analysis of real-world safety data presented at a major medical conference in Washington, D.C. show patients given the gut-selective Takeda biologic treatment ENTYVIO^® (vedolizumab) had fewer serious infections and adverse events than those on systemic tumour necrosis factor-alpha (TNFα)-antagonist therapy for ulcerative colitis (UC) and Crohn's disease (CD).

The results showed numerically lower rates of serious infections (SIs) [6.9% vs 10.1%; odds ratio (OR) 0.67, 95% confidence interval (CI) 0.41-1.07] and significantly lower rates of serious adverse events (SAEs) [7.1% vs 13.1%; OR 0.51, 95% CI 0.32-0.81] in patients treated with ENTYVIO^® (n=436) compared to TNFα-antagonist therapy (n=436).¹

This analysis of the VICTORY (Vedolizumab Health OuTComes in InflammatORY Bowel Diseases) Consortium was an oral presentation at the 2018 Digestive Disease Week^® (DDW) annual scientific meeting held June 2 to 5 in Washington, D.C.

"It is very useful for us as clinicians to have real-world safety information to help guide our decision-making for patients so we can offer them the best option for both improving their condition and preventing serious infections and adverse events," said Dr. Remo Panaccione, Director of the Inflammatory Bowel Disease Group at Foothills Medical Centre in Calgary, Alberta. "This latest data adds to the growing evidence that give us confidence in the safety profile of gut-selective therapy for ulcerative colitis and Crohn's disease."

Data from 872 UC and CD patients (334 and 538 respectively), of which 47% were male and having a median age of 35, from the VICTORY Consortium database, were analyzed. Patients receiving ENTYVIO^® were matched (1:1)* to patients on TNFα-antagonist therapy using propensity scores to control for baseline differences between groups. Among patients on biologic monotherapy (n=247; n=142 ENTYVIO^®), ENTYVIO^®-treated patients were observed to have numerically lower rates of SIs (4.1% vs 10.1%; OR 0.37, 95% CI 0.13-1.02) and significantly lower rates of SAEs (4.7% vs 14.5%; OR 0.29, 95% CI 0.12-0.73). Among patients who were on biologic therapy in combination with both steroids and an immunomodulator (n=137; n=69 ENTYVIO^®), rates of SIs (11.5% vs 13.9%, OR 0.81, 95% CI 0.31-2.07) and SAEs (14% vs 14%, OR 0.66, 95% CI 0.27-1.65) were similar between ENTYVIO^® and TNFα-antagonist treated patients. Concomitant immunosuppressive use was associated with an increased risk for both SI and SAE, and rates were similar between ENTYVIO^® and TNFα-antagonist therapy when using concomitant immunosuppressive therapy.¹**

"At Takeda patients come first with everything we do and that includes patient safety with our medicines. Gathering data about our medicines on an ongoing basis after they get into the "real world" is one of the ways we do this," said Gamze Yüceland, General Manager of Takeda Canada Inc. "Generating real world data on our medicines allows doctors to make the best decisions for their patients and for patients to have confidence in the therapies they receive. We are pleased to see this latest study reinforcing the safety profile of ENTYVIO^®."

Results from other Takeda-sponsored studies were also presented at DDW. Further safety analyses from the GEMINI studies support the safety profile of ENTYVIO^®. Results from a post-hoc analysis of interim data from the GEMINI long-term safety study (n=421; UC 190; CD 231) show nearly two-thirds of patients with UC (64%) and more than half with CD (55%) persisted with ENTYVIO^® treatment for three years, with low rates of discontinuation due to AEs, and treatment persistence rates higher in patients without versus with prior TNFα-antagonist failure (UC p=0.18: 69% vs 61%; CD p<0.01: 68% vs 51%).²

In addition, the GEMINI open-label extension (OLE) study showed that patients who were TNFα-antagonist therapy naïve experienced significantly fewer AEs (94 vs 275 per 100 patient-years) and SAEs (10 vs 18 per 100 patient-years) compared to TNFα-antagonist -experienced patients. Data from the GEMINI post-marketing (PM) setting were also analyzed and reported that a similar number of patients reported AEs in both groups, but limitations of PM safety reports, including incomplete data, must be considered when interpreting these results.³

For a full list of poster titles and authors at this year's DDW meeting visit, http://www.ddw.org/attendee-planning/online-planner.

About ulcerative colitis and Crohn's disease
Ulcerative colitis (UC) and Crohn's disease (CD) are the two most common forms of inflammatory bowel disease (IBD).⁴ Approximately 233,000 Canadians are living with UC and CD. More than 10,000 new cases are diagnosed each year, typically in patients in their 20s, though it can be diagnosed at any age, including in children.⁵ IBD has been labelled Canada's "national disease" due to Canada having among the highest rates in the world.⁶ 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.⁷ Sometimes a portion of the bowel needs to be surgically removed to bring patients relief.8 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.⁸

About ENTYVIO^®
ENTYVIO^® 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.⁹ 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.⁹

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.⁹ 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.⁹

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 44.¹⁰ 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 London¹¹ and Dr. Feagan was the lead author of the publication of the trial results in The New England Journal of Medicine in 2013.¹²

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
Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda's presence in emerging markets, are currently fueling the growth of Takeda. Around 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda's partners in health care in more than 70 countries. For more information, visit https://www.takeda.com/newsroom/.

Takeda Canada, located in Oakville, Ontario, is the Canadian sales and marketing organization of Takeda Pharmaceutical Company Limited. Takeda Canada is delivering better health for Canadians through leading innovations in gastroenterology and oncology. 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. YOURVANTAGE™ is a trademark of Takeda Canada.

*Propensity score matching (1:1) accounting for age, sex, prior disease-related hospitalization within the previous year, disease phenotype (stricturing or penetrating complication history for CD, disease extent for UC), disease severity, prior bowel surgery for CD, steroid refractoriness or dependence, and prior TNFα-antagonist failure.¹

** Rates of SIs and SAEs were compared using logistic regression analyses between matched patients; SIs were defined as requiring antibiotics or hospitalization or resulting in discontinuation or death, and SAEs as SI or non-infectious adverse events resulting in discontinuation or death.¹

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^1	Lukin D, Weiss A, Aniwan A, et al. Comparative Safety Profile of Vedolizumab and Tumor Necrosis Factor–Antagonist Therapy for Inflammatory Bowel Disease: A Multicenter Consortium Propensity Score - Matched Analysis. Presented at Digestive Disease Week (DDW) 2018, Washington D.C., #277
^2	Loftus EV, Vermeire S, Khalid JM, et al. Vedolizumab Treatment Persistence up to 3 Years: Post Hoc Analysis in Vedolizumab-Naïve Patients from the GEMINI Long-Term Safety Study. Presented at Digestive Disease Week (DDW) 2018, Washington D.C., #Sa1766
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^9	Takeda Canada Inc., ENTYVIO^® (vedolizumab) Product Monograph, May 3, 2017, 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/entyvio-pm-eng-03-may-2017-c.pdf May 25, 2018.
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^11	Sher J, Approval being sought for new treatment for Crohn's and colitis, The London Free Press, Aug. 21, 2013, accessed May 25, 2018, at: http://www.lfpress.com/2013/08/21/approval-being-sought-for-new-treatment-for-crohns-and-colitis
^12	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 May 25, 2018, at: http://www.nejm.org/doi/full/10.1056/NEJMoa1215734

SOURCE Takeda Canada Inc.

Media contact: Natacha Raphael, Corporate Communications, Takeda Canada Inc., Tel: [phone], [email protected]