OAKVILLE, Ontario – Results from the phase 3 VISIBLE 1 clinical trial evaluating the efficacy and safety of an investigational subcutaneous (SC) formulation of the gut-selective biologic ENTYVIO® (vedolizumab) were presented at the 2018 United European Gastroenterology (UEG) Week congress in Vienna, Austria.
The study looked at adult patients with moderately to severely active ulcerative colitis (UC) who achieved clinical response* at week 6 following two doses of open-label vedolizumab intravenous (IV) induction therapy.
The results show that at 52 weeks, a statistically significant proportion of patients receiving vedolizumab SC achieved clinical remission** compared to patients receiving placebo (46.2% vs. 14.3%; p<0.001). A similar rate of clinical remission was observed in the vedolizumab IV reference arm (42.6%).
“We are very encouraged with the results we are seeing with the subcutaneous formulation of vedolizumab. Patients are achieving important treatment goals with an efficacy and safety profile similar to that seen in patients on IV vedolizumab therapy,” said Dr. Vipul Jairath, holder of the John and Susan McDonald chair in inflammatory bowel disease at the Schulich School of Medicine and Dentistry, Western University, London, Ontario. “This is an important addition to our knowledge of this gut-selective therapy.”
“Vedolizumab is the first and only gut-selective therapy to treat ulcerative colitis and Crohn’s disease, so it is very useful to see this efficacy and safety result with the new subcutaneous formulation used in patients following IV induction therapy,” said Dr Guy Aumais, gastroenterologist at the Hôpital Maisonneuve-Rosemont in Montreal. “This is another important step forward in the treatment of patients with vedolizumab.” à Montréal
The VISIBLE 1 study also showed that subcutaneous (SC) vedolizumab was statistically superior to placebo in key secondary endpoints of mucosal healing*** (56.6% vs. 21.4%; p<0.001) and durable clinical responseǂ (64.2% vs. 28.6%; p<0.001). Vedolizumab SC was also numerically higher to placebo in achieving durable clinical remissionǂǂ (15.1% vs. 5.4%; p=0.076) and corticosteroid-free clinical remissionǂǂǂ (28.9% vs. 8.3%; p=0.067), with these results not being of statistical significance. Similar findings were observed for these endpoints in the vedolizumab IV reference arm.1 Additionally, a subgroup analysis showed clinical remission rates were significantly higher with vedolizumab SC compared to placebo in anti-tumor necrosis factor-alpha (TNFα)-naïve (53.7% vs. 18.9%; p<0.001) and anti-TNFα-failure patients (33.3% vs. 5.3%; p=0.023).1
“At Takeda our goal is to help meet the needs of patients. In inflammatory bowel disease one of the ways we can do that is by studying ways to make treatment easier for patients including the development of a subcutaneous formulation of vedolizumab. Putting patients first means giving them options that suit their needs and preferences,” said Gamze Yüceland, General Manager of Takeda Canada Inc.
“When you live with a chronic condition like Crohn’s disease or ulcerative colitis it’s really important to have different treatment options to manage your disease and improve your quality of life,” said Mina Mawani, President and CEO of Crohn's and Colitis Canada. “Takeda’s ongoing research demonstrates its commitment to supporting Canadians who live with inflammatory bowel disease.”
Adverse event rates, including severe adverse events and infections, were similar in the vedolizumab SC and IV groups. Injection-site reactions were mild and experienced by 9.4% of patients in the vedolizumab SC treatment group (vs. 0 in the placebo group), with none leading to treatment discontinuation. The rate of anti-vedolizumab antibodies (AVAs) was similar between the vedolizumab SC and IV groups (5.7% and 5.6%, respectively).1
VISIBLE 1 is a pivotal phase 3, randomized, double-dummy, double-blind, placebo-controlled study, with a vedolizumab IV reference arm, to evaluate the safety and efficacy of an investigational SC formulation of vedolizumab as maintenance therapy in adult patients with moderately to severely active UC who have achieved clinical response at week 6 following two doses of open-label vedolizumab IV therapy at weeks 0 and 2. The study enrolled 383 patients, all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or anti-TNFα therapy prior to being enrolled. Patients who achieved clinical response at week 6 (n=216, 56.4%) were randomized into one of three treatment groups, vedolizumab SC 108 mg and placebo IV (n=106), vedolizumab IV 300 mg and placebo SC (n=54), or placebo SC and placebo IV (n=56). Subcutaneous doses were administered every two weeks and intravenous doses were administered every eight weeks.1,2
About the VISIBLE clinical trial program The VISIBLE clinical trial program aims to assess the efficacy and safety of an investigational subcutaneous (SC) formulation of vedolizumab as maintenance therapy in adult patients with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD).
VISIBLE consists of three phase 3 studies involving over 1,000 patients which includes two randomized, double-blind, placebo-controlled studies examining the percentage of participants achieving clinical remission at week 52 in UC and CD, respectively, and an open-label extension study to determine the long-term safety and efficacy of vedolizumab SC consisting of patients who have completed one of the randomized clinical trials. , ,
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). 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. IBD has been labelled Canada’s “national disease” due to Canada having among the highest rates in the world. 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. 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.
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. 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.10
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.10
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. 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 and Dr. Feagan was the lead author of the publication of the trial results in The New England Journal of Medicine in 2013.
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.
* Clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from baseline (week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. ** Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore >1 point. *** Mucosal healing is defined as a Mayo endoscopic subscore of ≤1 point. ǂ Durable clinical response is defined as clinical response at weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from baseline (week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. ǂǂ Durable clinical remission is defined as clinical remission at weeks 6 and 52. ǂǂǂ 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. PBO: n=24, VDZ SC: n=45, VDZ IV: n=21.
ENTYVIO® is a registered trademark of Millennium Pharmaceuticals, Inc. and used under licence by Takeda Canada Inc. YOURVANTAGE™ is a trademark of Takeda Canada.
The subcutaneous formulation of ENTYVIO® is investigational and not approved for sale in Canada.
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2. Efficacy and safety of vedolizumab subcutaneously (SC) as maintenance therapy in ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT02611830 Accessed October 2018.
3. Efficacy and safety of vedolizumab subcutaneous (SC) as maintenance therapy in Crohn's disease. Available at: https://clinicaltrials.gov/ct2/show/NCT02611817 Accessed October 2018.
4. Vedolizumab subcutaneous long-term open-label extension study. Available at: https://clinicaltrials.gov/ct2/show/NCT02620046 Last accessed October 2018.
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6. Crohn’s and Colitis Canada, The Impact of IBD Report, Who is affected; accessed October 2018, at: http://crohnsandcolitis.ca/About-Us/Resources-Publications/Impact-of-IBD-Report
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9. Crohn’s and Colitis Foundation of America, The Facts about Inflammatory Bowel Disease, page 5, accessed October 2018, at: http://www.ccfa.org/assets/pdfs/updatedibdfactbook.pdf
10. 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
11. 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 October 2018, 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 October, 2018, at: http://www.lfpress.com/2013/08/21/approval-being-sought-for-new-treatment-for-crohns-and-colitis
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