ENTYVIO^® (vedolizumab) Shows Higher Rates of Mucosal Healing Versus TNFα-Antagonist Therapy in Ulcerative Colitis and Crohn’s Disease Patients 

OAKVILLE, Ontario – February 20, 2018 – New real-world data evaluating the comparative effectiveness of ENTYVIO^® (vedolizumab) and tumour necrosis factor-alpha (TNFα) antagonist therapy in patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) were recently presented in oral presentations at the 13th Congress of the European Crohn’s and Colitis Organization (ECCO).

These analyses observed that patients with UC treated with ENTYVIO^® compared to TNFα-antagonist therapy had statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 42%, HR 1.73, 95% CI 1.10-2.73) and clinical remission (54% vs 37%; HR 1.54, 95% CI 1.08-2.18), and numerically higher steroid-free clinical remission rates (49% vs 38%; HR 1.43, 95% CI 0.79-2.60). In CD, results reported statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 41%; HR 1.67, 95% CI 1.13-2.47), and numerically higher rates of clinical remission (38% vs 34%; HR 1.27, 95% CI 0.91-1.78) and steroid-free clinical remission (26% vs 18%; HR 1.75, 95% CI 0.90-3.43) compared to TNFα-antagonist therapy. These analyses were conducted by the VICTORY (Vedolizumab Health Outcomes in Inflammatory Bowel Diseases) Consortium.^[1],[2]

“The growing trend to develop real-world data such as these results is very helpful in augmenting the information acquired from clinical studies and giving physicians a better indication of what patients in our offices might expect,” said Dr. Brian Feagan, a gastroenterologist and Director of Robarts Clinical Trials at the Robarts Research Institute in London, Ontario. “This new information about achieving mucosal healing and clinical remission compared to other biologic therapies helps support the unique role of ENTYVIO^® in treating patients with ulcerative colitis and Crohn’s disease.”

Of the 646 UC and 1,122 CD VICTORY Consortium patients, data from 334 UC (n=167 ENTYVIO^® patients; 49% male; median age 36 years) and 538 CD (n=269 ENTYVIO^® patients; 44% male; median age 35 years) were analyzed. ENTYVIO^® patients were matched (1:1) * to patients on anti-TNFα therapy using propensity scores to control for baseline differences between groups. Researchers used Cox proportional hazard models to compare cumulative rates of mucosal healing (absence of ulcers or erosions for CD; Mayo endoscopic sub-score of 0 or 1 for UC), clinical remission (complete resolution of symptoms based on Physician Global Assessment), and steroid-free clinical remission (on steroids at baseline, tapered off, no repeat steroid prescription for 4 weeks). Findings were reported after adjusting for concomitant steroid or immunomodulator use, disease location (CD study only; isolated small bowel, ileocolonic, isolated colonic), and number of prior TNFα-antagonists used.^1,2

The Canadian real-world study, EVOLVE, was also presented at ECCO 2018. The aim was to evaluate real-world treatment patterns, clinical effectiveness, and safety in biologic-naïve, adult patients with UC and CD receiving ENTYVIO^® in Canada from May 2015 to Dec 2016. The key findings from this interim analysis were³:

• Approximately one-half of UC and one-quarter of CD patients were in clinical remission at 6 months post- ENTYVIO^® initiation
• Mucosal healing was observed in over two-thirds of UC and CD patients at 6 months post- ENTYVIO^® initiation
• Almost two-thirds of patients on a CS at ENTYVIO^® initiation were able to discontinue their CS
• These interim data support long-term effectiveness and tolerability of first-line ENTYVIO^® in UC and CD in real world clinical practice

And finally, new clinical data being presented at ECCO from the Phase 3b open-label prospective multicentre study (VERSIFY) evaluating the efficacy of ENTYVIO^® on complete mucosal healing (absence of ulcerations), endoscopic remission (SES-CD ≤4) and endoscopic response (50% decrease in SES-CD from baseline) provide insight into complete mucosal healing in CD.  The trial included 101 patients with moderately to severely active CD who had previously experienced treatment failure with corticosteroids, immunomodulators, and/or at least one TNFα-antagonist therapy. In this study, 46% of patients were categorized as having severe endoscopic activity at entry (SES-CD score of >15). Patients received ENTYVIO^® 300 mg intravenously at weeks 0, 2, 6 and then every 8 weeks for 26 weeks, followed by a 26-week extension period. Dose escalation was not permitted. Results at week 26 found ENTYVIO^® in an anti-TNFα-naïve setting induced complete mucosal healing (24%), endoscopic remission (20%) and endoscopic response (28%). Similar trends were observed in the overall population of CD patients.⁴

 “Takeda is committed to putting patients at the centre of everything we do, so investing in developing this real-world data about the effectiveness of ENTYVIO^® outside of clinical trials is very important for us because it provides a different and valuable perspective for physicians and patients,” said Kieran Leahy, Interim General Manager of Takeda Canada Inc. “We are pleased that this new data will help give Canadian physicians an even broader perspective of the potential benefits of ENTYVIO^® to treat inflammatory bowel disease.”

At this year’s ECCO congress, Takeda sponsored 33 posters and presentations on ENTYVIO^®, including other real-world analyses and clinical studies evaluating the impact of ENTYVIO^® on long-term remission, comparative efficacy/effectiveness, mucosal healing, resource utilization, and in special patient populations across CD and UC. For a full list of poster titles and authors, visit https://www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018.html.

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).^[3] 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.^[4] IBD has been labelled Canada’s “national disease” due to Canada having among the highest rates in the world.^[5] 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.^[6] 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.^[7]

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.^[8] 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.⁸

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.⁸ 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.⁸

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.^[9] 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^[10]and Dr. Feagan was the lead author of the publication of the trial results in The New England Journal of Medicine in 2013.^[11]

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 fuelling 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.

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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 baseline differences between groups including age, sex, prior UC/CD-related hospitalization within the previous year, disease history, disease extent, disease severity, steroid refractoriness or dependence, and prior TNFα-antagonist failure.