Osaka, Japan, August 8, 2019 --- Takeda Pharmaceutical Company Limited (“Takeda”) (TSE: 4502/NYSE: TAK) today announced that it has submitted a New Drug Application (NDA) to the Ministry of Health, Labour and Welfare in Japan for a subcutaneous (SC) formulation of vedolizumab, a gut-selective biologic for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC). Takeda proposes to make vedolizumab SC available in both syringe and pen options.
“This NDA filing is an important step in our commitment to deliver innovative medicines and treatment modalities that meet the needs of patients living with ulcerative colitis in Japan,” said Naoyoshi Hirota, Head of the Takeda Development Center Japan. “By making it possible to select the treatment modality that suits a patient's desired administration method and lifestyle, we are aiming to enhance the patient experience and help fulfill their needs.”
This NDA filing is based on the results of the VISIBLE 1 trial, a phase 3 clinical trial that evaluated the efficacy and safety of vedolizumab subcutaneous as maintenance therapy. In the VISIBLE 1 trial conducted in 216 adult patients with moderately to severely active ulcerative colitis, clinical response* was obtained at week 6 following two doses of open-label intravenous administrations of vedolizumab as an induction therapy at weeks 0 and 2[i]. The results of the VISIBLE 1 trial were presented at the 2018 United European Gastroenterology Week Congress in Vienna, Austria.
In evaluating the primary endpoint of VISIBLE 1, a statistically significant proportion of patients receiving vedolizumab subcutaneous 108 mg maintenance therapy administered every two weeks achieved clinical remission** compared to patients receiving placebo (46.2% vs. 14.3%; p<0.001) at week 52. A similar rate of clinical remission was observed in the vedolizumab intravenous 300 mg reference arm (42.6%) at week 52. Adverse event rates, including severe adverse events and infections, were similar in the vedolizumab subcutaneous and intravenous groups at week 52. Injection-site reactions were generally mild and experienced by 10.4% of patients in the vedolizumab subcutaneous treatment arm (vs. 0% in the placebo group), with none leading to treatment discontinuation1,2.
*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.
About the VISIBLE Trials
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).
VISIBLE 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 SC3,4,5.
About Ulcerative Colitis
Ulcerative colitis is one of the most common forms of inflammatory bowel disease (IBD)6, affecting over 220,000 people in Japan. UC is a chronic, relapsing, remitting, inflammatory condition of the gastrointestinal (GI) tract that is often progressive in nature7,8. UC involves the innermost lining of the large intestine and often presents with symptoms of abdominal discomfort and loose bowel movements, including blood or pus. The cause of UC is not fully understood, but recent research suggests hereditary, genetic, and environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to UC.
About Entyvio® (vedolizumab)
Vedolizumab is a gut-selective biologic and is currently approved as an intravenous formulation9. It is a humanized monoclonal antibody designed to specifically antagonize the α4β7 integrin, inhibiting the binding of α4β7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1)10. MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract11. α4β7 integrin is expressed on a subset of circulating white blood cells10. These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis and Crohn’s disease10,12,13. By inhibiting α4β7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.
The drug information contained herein is intended for the disclosure of Takeda corporate information and is not intended to advertise or promote any prescription drug, including those under development.
[i] Sandborn WJ, Baert F, Danese S, et al. Efficacy and safety of a new vedolizumab subcutaneous formulation for ulcerative colitis: results of the VISIBLE 1 phase 3 trial. United European Gastroenterology J. 2018;6(Supplement 1).
2 Takeda Data on File. 2019.
3 Efficacy and safety of vedolizumab subcutaneously (SC) as maintenance therapy in ulcerative colitis. Available at: https://clinicaltrials.gov/ct2/show/NCT02611830. Last updated: August 27, 2018. Last accessed: April 2019.
4 Efficacy and safety of vedolizumab subcutaneous (SC) as maintenance therapy in Crohn's disease. Available at: https://clinicaltrials.gov/ct2/show/NCT02611817. Last updated: December 24, 2018. Last accessed: April 2019.
5 Vedolizumab subcutaneous long-term open-label extension study. Available at: https://clinicaltrials.gov/ct2/show/NCT02620046. Last updated December 24, 2018. Last accessed: April 2019.
6 Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627-1640.
7 Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590-1605.
8 Torres J, Billioud V, Sachar DB, et al. Ulcerative colitis as a progressive disease: the forgotten evidence. Inflamm Bowel Dis. 2012;18:1356-1363.
9 Entyvio Prescribing Information. Available at: https://general.takedapharm.com/ENTYVIOPI. Last updated: February 2018. Last accessed: April 2019.
10 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.
11 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.
12 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.
13 Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its roles in the pathogenesis of IBD. Inflamm Bowel Dis. 2008;14:1298-1312.