Data to be discussed with global health authorities, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)
OSAKA, Japan I July 19, 2018 I Takeda Pharmaceutical Company Limited [TSE:4502] (“Takeda”) today announced top-line results from the VISIBLE 1 clinical trial evaluating the efficacy and safety of an investigational subcutaneous (SC) formulation of vedolizumab for maintenance therapy in 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. In the primary endpoint of the trial, a statistically significant proportion of patients receiving vedolizumab SC beginning at week 6 and every two weeks following achieved clinical remission** at week 52 compared to placebo. The safety data were consistent with the known safety profile of vedolizumab, and no new safety signals were identified. Further data from the trial will be presented at a future scientific congress.
“Meeting the primary endpoint of the VISIBLE 1 trial marks an exciting milestone in our approach to developing new ways to meet the needs of the ulcerative colitis patient community,” said Asit Parikh, MD PhD, Head of Takeda’s Gastroenterology Therapeutic Area Unit. “These results are encouraging and build on vedolizumab’s robust clinical profile with more than 200,000 patient years of exposure. We plan to discuss these data with health authorities with the aim of bringing this innovative treatment option to patients.”
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 384 patients, all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or tumor necrosis factor-alpha (TNFα)-antagonist therapy prior to being enrolled. Patients who achieved clinical response at week 6 were randomized into one of three treatment groups, vedolizumab SC 108 mg and placebo IV, vedolizumab IV 300 mg and placebo SC, or placebo SC and placebo IV. Subcutaneous doses were administered every two weeks and intravenous doses were administered every eight weeks.
Additional endpoints assessed in VISIBLE 1 include the proportion of subjects achieving mucosal healing at week 52,*** durable clinical response,ǂ durable clinical remissionǂǂ and corticosteroid-free clinical remission at week 52.ǂǂǂ
| |
| * Clinical response is defined as a reduction in 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 greater than >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 participants using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission at week 52. Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point. |
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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 two of the most common forms of inflammatory bowel disease (IBD). Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal (GI) tract that are often progressive in nature. UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus. CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine. UC commonly presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus. CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss. The cause of UC or CD 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 UC or CD.
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 over 200,000 patient years of exposure to date.
Therapeutic Indications
Ulcerative colitis
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis 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.
Crohn’s disease
Vedolizumab is 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 either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.
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) 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.
SOURCE: Takeda Pharmaceutical Co
Post Views: 18
Data to be discussed with global health authorities, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)
OSAKA, Japan I July 19, 2018 I Takeda Pharmaceutical Company Limited [TSE:4502] (“Takeda”) today announced top-line results from the VISIBLE 1 clinical trial evaluating the efficacy and safety of an investigational subcutaneous (SC) formulation of vedolizumab for maintenance therapy in 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. In the primary endpoint of the trial, a statistically significant proportion of patients receiving vedolizumab SC beginning at week 6 and every two weeks following achieved clinical remission** at week 52 compared to placebo. The safety data were consistent with the known safety profile of vedolizumab, and no new safety signals were identified. Further data from the trial will be presented at a future scientific congress.
“Meeting the primary endpoint of the VISIBLE 1 trial marks an exciting milestone in our approach to developing new ways to meet the needs of the ulcerative colitis patient community,” said Asit Parikh, MD PhD, Head of Takeda’s Gastroenterology Therapeutic Area Unit. “These results are encouraging and build on vedolizumab’s robust clinical profile with more than 200,000 patient years of exposure. We plan to discuss these data with health authorities with the aim of bringing this innovative treatment option to patients.”
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 384 patients, all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or tumor necrosis factor-alpha (TNFα)-antagonist therapy prior to being enrolled. Patients who achieved clinical response at week 6 were randomized into one of three treatment groups, vedolizumab SC 108 mg and placebo IV, vedolizumab IV 300 mg and placebo SC, or placebo SC and placebo IV. Subcutaneous doses were administered every two weeks and intravenous doses were administered every eight weeks.
Additional endpoints assessed in VISIBLE 1 include the proportion of subjects achieving mucosal healing at week 52,*** durable clinical response,ǂ durable clinical remissionǂǂ and corticosteroid-free clinical remission at week 52.ǂǂǂ
| |
| * Clinical response is defined as a reduction in 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 greater than >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 participants using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission at week 52. Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point. |
###
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 two of the most common forms of inflammatory bowel disease (IBD). Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal (GI) tract that are often progressive in nature. UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus. CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine. UC commonly presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus. CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss. The cause of UC or CD 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 UC or CD.
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 over 200,000 patient years of exposure to date.
Therapeutic Indications
Ulcerative colitis
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis 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.
Crohn’s disease
Vedolizumab is 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 either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.
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) 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.
SOURCE: Takeda Pharmaceutical Co
Post Views: 18
