Takeda Receives Positive CHMP Opinion for Subcutaneous Formulation of Vedolizumab for use as Maintenance Therapy in Adults with Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease
- Category: Antibodies
- Published on Saturday, 29 February 2020 09:11
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− If approved, the additional treatment modality will provide more options for how patients in Europe receive the gut-selective biologic vedolizumab
− Recommendation brings vedolizumab one step closer to becoming the only maintenance therapy with both intravenous and subcutaneous formulation options for patients with ulcerative colitis or Crohn’s disease
OSAKA, Japan I February 28, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of a subcutaneous (SC) formulation of the gut-selective biologic vedolizumab for use as maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). Takeda proposes to make vedolizumab SC available in both a pre-filled syringe and a pre-filled pen.
“Ulcerative colitis and Crohn’s disease are life-long diseases and it is important that patients have treatment options that suit their different preferences and lifestyles. We look forward to the European Commission’s decision and the opportunity to bring a subcutaneous formulation of vedolizumab to these patients across Europe.”
The CHMP opinion will now be reviewed by the European Commission. If approved, vedolizumab will become the only maintenance therapy for UC or CD with both intravenous and subcutaneous formulations across the European Union, providing greater options for how patients receive their treatment.
“Today’s positive CHMP opinion marks a key step forward in our goal to provide greater options to patients with ulcerative colitis and Crohn’s disease,” said Adam Zaeske, Head, GI Franchise, Europe and Canada Business Unit, Takeda. “Ulcerative colitis and Crohn’s disease are life-long diseases and it is important that patients have treatment options that suit their different preferences and lifestyles. We look forward to the European Commission’s decision and the opportunity to bring a subcutaneous formulation of vedolizumab to these patients across Europe.”
The positive opinion from the CHMP was based on the pivotal phase 3 VISIBLE trials which assessed the safety and efficacy of a SC formulation of vedolizumab as maintenance therapy in adult patients with moderately to severely active UC or CD who achieved clinical response* at week 6 following two doses of open-label vedolizumab intravenous (IV) therapy at weeks 0 and 2.1,2,3 Data from a long-term, open-label extension study of patients from VISIBLE 1 and VISIBLE 2 was also considered.4
|* VISIBLE 1 UC: 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.2|
|VISIBLE 2 CD: Clinical response is defined as a ≥70 point decrease in Crohn's Disease Activity Index (CDAI) score from baseline (week 0).5|
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) or Crohn’s disease (CD).
The VISIBLE program consists of three phase 3 studies involving over 1,000 UC and CD patients which includes two randomized, double-blind, placebo-controlled studies examining the proportion of patients achieving clinical remission at week 52, and an open-label extension study to determine the long-term safety and efficacy of vedolizumab SC.2,3,4
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).6 Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal tract, with CD potentially progressing over time.7,8 UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus.9,10 CD can also affect the entire thickness of the bowel wall while UC only involves the innermost lining of the large intestine.9,10 UC commonly presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus.9,11 CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss.7 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.9,12,13
About Entyvio® (vedolizumab)
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.14,15 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).16 MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.17 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.16 These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).16,18,19 By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.16
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.14,15 Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with more than 415,000 patient years of exposure to date.5
Therapeutic Indications for vedolizumab IV
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.
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/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.
For more information, visit https://www.takeda.com
1 Sandborn WJ, Baert F, Danese S, et al. Efficacy and safety of a new vedolizumab subcutaneous formulation in ulcerative colitis: VISIBLE 1 randomized trial. Gastroenterology. 2019. DOI: https://doi.org/10.1053/j.gastro.2019.08.027.
2 Efficacy and safety of vedolizumab subcutaneously (SC) as maintenance therapy in ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT02611830. Last updated: January 23, 2020. Last accessed: February 2020.
3 Efficacy and safety of vedolizumab subcutaneous (SC) as maintenance therapy in Crohn's disease. Available at: https://clinicaltrials.gov/ct2/show/NCT02611817. Last updated: November 12, 2019. Last accessed: February 2020.
4 Vedolizumab subcutaneous long-term open-label extension study. Available at: https://clinicaltrials.gov/ct2/show/NCT02620046. Last updated: May 6, 2019. Last accessed: February 2020.
5 Takeda Data on File. 2019.
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12 Henckaerts L, Pierik M, Joossens M, et al. Mutations in pattern recognition receptor genes modulate seroreactivity to microbial antigens in patients with inflammatory bowel disease. Gut. 2007;56:1536-1542.
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14 Entyvio Prescribing Information. Available at: https://general.takedapharm.com/ENTYVIOPI. Last updated: May 2019. Last accessed: February 2020.
15 Entyvio EPAR _ 20/02/2019 Entyvio - EMEA/H/C/002782_ European Medicines Agency - Entyvio _ Annex I Summary of product characteristics. Committee For Medicinal Products For Human Use. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/entyvio. Last updated: April 2019. Last accessed: February 2020.
16 Soler D, Chapman T, Yang LL, et al. The binding specificity and selective antagonism of vedolizumab, an anti-α4β7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330:864-875.
17 Briskin M, Winsor-Hines D, Shyjan A, et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol. 1997;151:97‑110.
18 Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its roles in the pathogenesis of IBD. Inflamm Bowel Dis. 2008;14:1298‑1312.
19 Wyant T, Fedyk E, Abhyankar B. An overview of the mechanism of action of the monoclonal antibody vedolizumab. J Crohns Colitis. 2016;10:1437-1444.
SOURCE: Takeda Pharmaceutical Co