Takeda Drug Achieves Primary Endpoint of Clinical Remission in Moderately to Severely Active Ulcerative Colitis

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  • A statistically significant proportion of patients achieved clinical remission at week 52 compared to placebo
  • Vedolizumab is a humanized monoclonal antibody specifically designed to mediate inflammation in UC and CD patients
  • In a previous study, Vedolizumab, achieved superior results in mucosal healing vs TNFα-antagonist therapy

Takeda Pharmaceutical Company Limited [TSE:4502] (“Takeda”) announced on 7/19/18 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.

Vedolizumab (Entyvio) 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.

In February of 2018, Takeda announced results from the VICTORY consortium data that indicated higher rates of mucosal healing for vedolizumab vs TNFα-antagonist therapy in patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD).