TORONTO, Ontario – March 30, 2023 – Takeda Canada Inc. (“Takeda”) is pleased to announce the positive data from the Phase 4 EARNEST study of vedolizumab for the treatment of chronic pouchitis has been published in the New England Journal of Medicine (NEJM). The NEJM article is titled “Vedolizumab for the Treatment of Chronic Pouchitis.”
Pouchitis is a condition that can follow the surgical creation of an ileal pouch (known as ileal pouch-anal anastomosis or IPAA) to aid stool retention in patients with ulcerative colitis. Pouchitis can cause fecal incontinence, abdominal discomfort, and bleeding.2 Chronic pouchitis, defined by symptom duration greater than four weeks, can develop in approximately one-fifth of these patients.3
The published results showed the Phase 4 EARNEST study met its primary efficacy endpoint of clinical and endoscopic remission, as measured by modified pouchitis disease activity index (mPDAI), at Week 14 in 31% of participants (16 out of 51) receiving vedolizumab versus 10% (5 out of 51) receiving placebo (95% CI: 5 to 38; p=0.013). This improved outcome compared with placebo was also seen at the equivalent secondary endpoint at Week 34 (35% of vedolizumab patients [18 out of 51] achieved mPDAI remission compared with 18% [9 out of 51] on placebo [95% CI: 0 to 35 p.p difference]).1
Beyond mPDAI remission, patients receiving vedolizumab also demonstrated improved clinical response at both Week 14 and Week 34 over placebo, with a difference at Week 14 of 30 percentage points (p.p.) (95% CI, 8 to 48), and a Week 34 difference of 22p.p. (95% CI, 2 to 40). Serious adverse events occurred in 6% (3 out of 51) and 8% (4 out of 51) of patients in the vedolizumab and placebo groups, respectively.1 No new safety signals were identified.
EARNEST is a randomized, double-blind, placebo-controlled multicenter study that evaluated the efficacy and safety of vedolizumab IV in the treatment of 102 adult patients with UC who had undergone a proctocolectomy and IPAA, had developed active chronic pouchitis, and had inadequate response with or lost response to antibiotics therapy. Canadian investigators played an important role in the development and execution of this study.
“This study represents the first placebo-controlled trial demonstrating the efficacy of a biologic in patients with active chronic pouchitis. The trial demonstrated superiority of vedolizumab over placebo across a range of clinical, endoscopic, and histological endpoints showing a consistency of treatment effect. These data provide a highly effective treatment option for patients with active chronic pouchitis who have failed or have become dependent upon antibiotics and represent an important step forward for patients with this condition.”
“The trial shows a clinically meaningful benefit of vedolizumab therapy in a group of patients for whom existing treatments are either ineffective or unproven.”
“Pouchitis is a common and potentially serious inflammatory condition for patients with ulcerative colitis who have a pouch formed following a colectomy. The data clearly demonstrates an important opportunity for a group of these patients who previously had limited treatment options once antibiotics are no longer effective or tolerated.”
ENTYVIO (vedolizumab) is approved by Health Canada for the treatment of moderately to severely active Ulcerative Colitis and Crohn's Disease. The safety and efficacy of ENTYVIO for the treatment of pouchitis have not yet been evaluated by Health Canada.
Patients with ulcerative colitis (UC) may require removal of their colon and rectum (proctocolectomy), and the surgical creation of an ileal pouch (ileal pouch-anal anastomosis or IPAA) to aid stool retention. Pouchitis, where inflammation and irritation are seen in the lining of the new pouch, is the most common complication of an IPAA, affecting approximately 50% of patients.3 Acute pouchitis may respond to antibiotic therapy, however there are currently no approved therapies indicated for active chronic pouchitis including the refractory form of pouchitis, which does not respond to antibiotic therapy, and where patients frequently relapse.3 Refractory pouchitis affects 10-15% of patients with pouchitis, and can have a considerable impact on their quality of life, causing fecal urgency, incontinence, straining during defecation, bleeding, abdominal or pelvic discomfort, fever and malaise.2,4,5,6 The prevalence of all pouchitis has been calculated to be 12 to 18 patients per 100,000 in Western countries.7
Vedolizumab is a gut-selective biologic approved by Health Canada in both intravenous (IV) and subcutaneous (SC) formulations. It’s approved for the treatment of adults with moderately to severely active, ulcerative colitis (UC) for patients who have had an inadequate response, loss of response to, or were intolerant to either conventional therapy or infliximab, a tumor necrosis factor‐alpha (TNFα) antagonist, and Crohn’s disease (CD), for patients 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.8
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)9. MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract10. The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.11 These cells have been shown to play a role in mediating the inflammatory process in UC and CD.11,11,12 By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.11
Vedolizumab has been granted marketing authorization in over 70 countries, including Canada, the United States and European Union, with more than 1,000,000 patient years of exposure to date.13
Takeda Canada Inc. is the Canadian organization of Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE: TAK), a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discovering and delivering life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, 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 and regions. For more information, visit: takeda.com/en-ca.
Takeda Canada Inc.