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Retrospective Real-World Comparative Analysis Highlights Safety of Vedolizumab and Anti-TNFα Therapies in Biologic-Naïve Patients with Ulcerative Colitis or Crohn’s Disease

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Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced results from a retrospective chart review study (EVOLVE), which investigated the likelihood of serious adverse events and serious infections with vedolizumab and anti-tumor necrosis factor-alpha (anti-TNFα) therapies in biologic-naïve patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) in real-world clinical practice. These data were announced in an oral presentation at UEG Week 2019, held in Barcelona, Spain.

Data from over 1,000 biologic-naïve patients with UC or CD receiving vedolizumab or an anti-TNFα therapy (adalimumab, infliximab, golimumab, or certolizumab pegol) were collected, with the incidence rate (per 100 person-years) for serious adverse events and serious infections estimated per cohort. The incidence rates for the first occurrence of a serious adverse event (vedolizumab: 4.6 [3.5-6.8]; anti-TNFα: 10.3 [9.5-14.9]) and serious infections (vedolizumab: 1.4 [0.8-2.5]; anti-TNFα: 2.6 [1.7-4.3]) were estimated to be lower with vedolizumab treatment.1 Also, gastrointestinal infections were estimated to be lower in vedolizumab-treated vs. anti-TNFα-treated patients (1.1% vs. 4.3%, respectively, p<0.01).1 Similar trends were observed when results were segmented by UC and CD.1*

“While retrospective chart reviews have limitations and are not conclusive, real-world evidence can enhance our understanding of the performance of treatments in clinical practice, providing valuable information to assist physicians in the selection of appropriate therapy for patients. Sharing the latest real-world evidence, such as the EVOLVE study, with scientific and clinical communities, forms an integral part of Takeda’s ongoing commitment towards improving patient care,” said Michelle Luo, PhD, Head of Global Outcomes Research-Gastroenterology, Takeda.

The EVOLVE study is one of nine Takeda vedolizumab abstracts accepted for presentation at the annual UEG Week congress, with new data being presented from clinical studies that assess the efficacy and safety of vedolizumab, as well as new evaluations to understand the role of clinical decision support tools in the management of inflammatory bowel disease.

* Data revised following abstract acceptance

About the EVOLVE Study

The EVOLVE study was a retrospective chart review of real-world data in biologic-naïve patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) treated with vedolizumab or anti-tumor necrosis factor-alpha (anti-TNFα) therapies. Patients had initiated treatment with vedolizumab or anti-TNFα therapies (adalimumab, infliximab, golimumab, or certolizumab pegol) between May 2014 and March 2018 and were followed for ≥six months. Evidence was collected from 1,095 biologic-naïve patients from 42 sites in Canada, Greece and the United States; 598 were treated with vedolizumab (UC=380; CD=218), and 497 were treated with anti-TNFα therapies (UC=224; CD=273).1 A Cox proportional hazards model adjusted for baseline patient characteristics was used to compare incidence rates between treatment cohorts.2

A retrospective chart review is a type of research design in which patient medical records are collected from real-world clinical practice to answer research questions.3,4 The data evaluated were collected before the research had begun, and therefore were not originally intended for investigative purposes nor to answer specific research questions. While retrospective chart reviews are important for advancing physician understanding of the performance of treatments in clinical practice, the records reviewed may not be complete and as such chart reviews can be more prone to bias as compared to prospective studies.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).5 Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal tract that are often progressive in nature.6,7 UC only involves the large intestine as opposed to CD, which can affect any part of the GI tract from mouth to anus.8,9 CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine.7,8 UC commonly presents with symptoms of abdominal discomfort and loose bowel movements, including blood or pus.8,10 CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss.6 The cause of UC or CD is not fully understood; however, recent research suggests hereditary, genetic, environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to UC or CD.8,11,12

About Entyvio® (vedolizumab)

Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.13,14 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).15 MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.16 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.15 These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).15,17,18 By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.15

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.13,14 Vedolizumab IV has been granted marketing authorization in over 60 countries, including the United States and European Union, with more than 330,000 patient years of exposure to date.19

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.

Important Safety Information

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Special warnings and special precautions for use

Vedolizumab should be administered by a healthcare professional prepared to manage hypersensitivity reactions, including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering vedolizumab. Observe patients during infusion and until the infusion is complete.

Infusion-related reactions

In clinical studies, infusion-related reactions (IRR) and hypersensitivity reactions have been reported, with the majority being mild to moderate in severity. If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of vedolizumab must be discontinued immediately and appropriate treatment initiated (e.g., epinephrine and antihistamines). If a mild to moderate IRR occurs, the infusion rate can be slowed or interrupted and appropriate treatment initiated (e.g., epinephrine and antihistamines). Once the mild or moderate IRR subsides, continue the infusion. Physicians should consider pre-treatment (e.g., with antihistamine, hydrocortisone and/or paracetamol) prior to the next infusion for patients with a history of mild to moderate IRR to vedolizumab, in order to minimize their risks.

Infections

Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive activity. Physicians should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier. Vedolizumab treatment is not to be initiated in patients with active, severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections until the infections are controlled, and physicians should consider withholding treatment in patients who develop a severe infection while on chronic treatment with vedolizumab. Caution should be exercised when considering the use of vedolizumab in patients with a controlled chronic severe infection or a history of recurring severe infections. Patients should be monitored closely for infections before, during and after treatment. Before starting treatment with vedolizumab, screening for tuberculosis may be considered according to local practice. Some integrin antagonists and some systemic immunosuppressive agents have been associated with progressive multifocal leukoencephalopathy (PML), which is a rare and often fatal opportunistic infection caused by the John Cunningham (JC) virus. By binding to the α4β7 integrin expressed on gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect specific to the gut. Although no systemic immunosuppressive effect was noted in healthy subjects, the effects on systemic immune system function in patients with inflammatory bowel disease are not known. Healthcare professionals should monitor patients on vedolizumab for any new onset or worsening of neurological signs and symptoms, and consider neurological referral if they occur. If PML is suspected, treatment with vedolizumab must be withheld; if confirmed, treatment must be permanently discontinued. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body, clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. The progression of deficits usually leads to death or severe disability over weeks or months.

Malignancies

The risk of malignancy is increased in patients with ulcerative colitis and Crohn’s disease. Immunomodulatory medicinal products may increase the risk of malignancy.

Prior and concurrent use of biological products

No vedolizumab clinical trial data are available for patients previously treated with natalizumab. No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are available. Therefore, the use of vedolizumab in such patients is not recommended.

Vaccinations

Prior to initiating treatment with vedolizumab all patients should be brought up to date with all recommended immunizations. Patients receiving vedolizumab may receive non-live vaccines (e.g., subunit or inactivated vaccines) and may receive live vaccines only if the benefits outweigh the risks.

Adverse reactions include: nasopharyngitis, headache, arthralgia, upper respiratory tract infection, bronchitis, influenza, sinusitis, cough, oropharyngeal pain, nausea, rash, pruritus, back pain, pain in extremities, pyrexia, fatigue and anaphylaxis.

Please consult with your local regulatory agency for approved labeling in your country.

For U.S. audiences, please see the full Prescribing Information including Medication Guide for ENTYVIO®.

For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO®.

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, Gastroenterology (GI), Rare Diseases, and Neuroscience. 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 https://www.takeda.com

###

References

1 Yarur A, Mantzaris GJ, Kopylov U, et al. Real-world safety of vedolizumab and anti-TNF therapies in biologic-naïve ulcerative colitis and Crohn’s disease patients: Results from the EVOLVE study. Presented at UEG Week 2019. Oral presentation OP005.

2 Yarur A, Mantzaris G, Silverberg M, et al. P573 Real-world effectiveness and safety of vedolizumab and anti-TNF in biologic-naive ulcerative colitis patients: Results from the EVOLVE study. J Crohns Colitis. 2019;13:S400–S401.

3 Vassar M and Holzmann M. The retrospective chart review: important methodological considerations. J Educ Eval Health Prof. 2013;10:12.

4 Panacek EA. Performing chart review studies. Air Med J. 2007;26:206-10.

5 Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369:1627-1640.

6 Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590-1605.

7 Torres J, Billioud V, Sachar DB, et al. Ulcerative colitis as a progressive disease: the forgotten evidence. Inflamm Bowel Dis. 2012;18:1356-1363.

8 Ordas I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380:1606-1619.

9 Feuerstein JD, Cheifetz AS. Crohn’s disease: Epidemiology, diagnosis and management. Mayo Clin Proc. 2017;92:1088-1103.

10 Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004;126:1518-1532.

11 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.

12 Kaser A, Zeissig S, Blumberg RS. Genes and environment: How will our concepts on the pathophysiology of IBD develop in the future? Dig Dis. 2010;28:395-405.

13 Entyvio Prescribing Information. Available at: https://general.takedapharm.com/ENTYVIOPI. Last updated: May 2019. Last accessed: October 2019.

14 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. https://www.ema.europa.eu/en/medicines/human/EPAR/entyvio. Last updated: April 2019. Last accessed: October 2019.

15 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.

16 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.

17 Eksteen B, Liaskou E, Adams DH. Lymphocyte homing and its roles in the pathogenesis of IBD. Inflamm Bowel Dis. 2008;14:1298‑1312.

18 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.

19 Takeda Data on File. 2019.

Contact information

Media outside Japan
Luke Willats
luke.willats@takeda.com
+41-44-555-1145

Japanese Media
Tatsuhiro Kanoo
tatsuhiro.kanoo@takeda.com
+81 (0) 3-3278-2095

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