U.S. FDA Approves Subcutaneous Administration of Takeda’s ENTYVIO® (vedolizumab) for Maintenance Therapy in Moderately to Severely Active Crohn’s Disease

• ENTYVIO is Now Available in the U.S. in Both IV and Subcutaneous Administrations for Maintenance Treatment of Adults with Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease

OSAKA, Japan I April 19, 2024 and CAMBRIDGE, MA, USA I April 18, 2024 –ITakeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved ENTYVIO® (vedolizumab) subcutaneous (SC) administration for maintenance therapy in adults with moderately to severely active Crohn’s disease (CD) after induction therapy with intravenous (IV) ENTYVIO.¹ The subcutaneous administration of ENTYVIO was also approved by FDA in September 2023 for the maintenance treatment of adults with moderately to severely active ulcerative colitis (UC) and is available in the U.S. as a single-dose prefilled pen (ENTYVIO Pen).^*

The approval is based on the VISIBLE 2 Study (SC CD Trial), a Phase 3, randomized, double-blind, placebo-controlled trial, which assessed the safety and efficacy of an SC formulation of ENTYVIO as maintenance therapy in adult patients with moderately to severely active CD who had clinical response^** at Week 6 following two doses of open-label vedolizumab intravenous therapy at Weeks 0 and 2.¹ The primary endpoint was clinical remission^*** at Week 52, which was defined as a total Crohn’s Disease Activity Index (CDAI) score of ≤150.

“Crohn’s disease is a complex and usually progressive disease for which an appropriate management plan is critical. My primary goal as a clinician is always to get patients to achieve remission. In VISIBLE 2, about half of patients treated with ENTYVIO SC achieved long-term clinical remission,” said Timothy Ritter, MD, senior medical director, Department of Research and Education, GI Alliance Research and assistant professor of medicine, TCU School of Medicine. “The data from VISIBLE 2 reaffirm the well-established efficacy profile of ENTYVIO, regardless of route of administration.”

In VISIBLE 2, a total of 409 patients were randomized at Week 6 in a double-blind fashion (2:1) to ENTYVIO 108 mg administered by SC injection or placebo every 2 weeks.¹ Eligible patients included patients who had experienced an inadequate response to, loss of response to, or intolerance to at least one of the following: corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate), or tumor necrosis factor (TNF) blockers (including primary non-responders).

A statistically significant proportion of patients receiving ENTYVIO SC 108 mg maintenance therapy administered every 2 weeks achieved long-term clinical remission^*** compared to patients receiving placebo (48% vs. 34%; p<0.01) at Week 52.¹ In clinical studies, the ENTYVIO SC safety profile was generally consistent with the known safety profile of ENTYVIO IV, with the addition of injection site reactions (including injection site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria and edema) as an adverse reaction for ENTYVIO SC. The most common adverse reactions reported with ENTYVIO IV (incidence ≥3% and ≥1% higher than placebo) were nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.

“The approval of subcutaneous ENTYVIO in Crohn’s disease delivers on our goal of providing treatment options that can help patients achieve remission of their ulcerative colitis or Crohn’s disease, while also providing them flexibility and choice of route of administration. With ENTYVIO Pen, patients have the option of administering their maintenance treatment at home or on the go,” said Brandon Monk, senior vice president, head, U.S. Gastroenterology Business Unit, Takeda. “Our development of a subcutaneous option demonstrates Takeda’s commitment to meeting the very real needs of those living with gastrointestinal diseases.”

_{*Please refer to “U.S. FDA Approves Subcutaneous Administration of Takeda’s ENTYVIO® (vedolizumab) for Maintenance Therapy in Moderately to Severely Active Ulcerative Colitis”, dated September 27, 2023.
**Clinical response is defined as a ≥70-point decrease in Crohn’s Disease Activity Index (CDAI) score from baseline (Week 0).}¹
_{***Clinical remission is defined as CDAI score of ≤150 at Week 52.}¹

Takeda does not expect a material impact on the consolidated financial statements as a result of this approval.

About ENTYVIO (vedolizumab)

Vedolizumab is a biologic therapy and is approved for intravenous (IV) and subcutaneous (SC) administration (approvals vary by market).^1,2 Vedolizumab SC has been granted marketing authorization in the United States, European Union and more than 50 countries. Vedolizumab IV has been granted marketing authorization in more than 70 countries, including the United States and European Union. Globally, vedolizumab IV and SC have more than one million patient years of exposure to date.³ Vedolizumab 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).⁴ MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.⁵ The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.⁴ These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis and Crohn’s disease.^4,6,7 By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.⁴

INDICATIONS

Adult Ulcerative Colitis (UC):

ENTYVIO is indicated in adults for the treatment of moderately to severely active UC.

Adult Crohn’s Disease (CD):

ENTYVIO is indicated in adults for the treatment of moderately to severely active CD.

DOSAGE FORMS & STRENGTHS:

• ENTYVIO Intravenous (IV) Infusion: 300 mg vedolizumab
• ENTYVIO Subcutaneous (SC) Injection: 108 mg vedolizumab

Please click for Full U.S. Prescribing Information

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).⁸ Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal tract.^9,10 UC only involves the large intestine as opposed to CD, which can affect any part of the GI tract from mouth to anus.^11,12 CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine.^11,12 UC can present with symptoms of abdominal discomfort or loose bowel movements, including blood.^11,13 CD can present with symptoms of abdominal pain, diarrhea, and weight loss.¹² The cause of UC or CD is not fully understood; however, research suggests that an interplay between environmental factors, genetics, and intestinal microbiota may contribute to the development of UC or CD.^11,14,9

Takeda’s Commitment to Gastroenterology

With this latest milestone, Takeda continues to demonstrate a commitment to meeting the very real needs of those living with gastrointestinal (GI) diseases. We believe that GI and liver diseases are life-disrupting conditions. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. With more than 35 years of experience in gastroenterology, Takeda has made significant strides in addressing patient needs with treatments for inflammatory bowel disease (IBD), eosinophilic esophagitis (EoE), acid-related diseases, short bowel syndrome (SBS) and motility disorders. We are making significant strides toward closing the gap on new areas of unmet need. Together with researchers, patient groups and more, we are working to advance scientific research and clinical medicine in GI.

About Takeda

Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience, and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.

References

1. ENTYVIO (vedolizumab) Prescribing Information. Takeda Pharmaceuticals U.S.A., Inc.
2. ENTYVIO Summary of Product Characteristics (SmPC). Available at: https://www.ema.europa.eu/en/documents/product-information/entyvio-epar-product-information_en.pdf
3. Data on file. Takeda Pharmaceuticals.
   
   
4. Soler D, Chapman T, Yang LL, et al. J Pharmacol Exp Ther. 2009;330(3):864-875.
   
   
5. Briskin M, Winsor-Hines D, Shyjan A, et al. Am J Pathol. 1997;151:97 110.
   
   
6. Eksteen B, Liaskou E, Adams DH. Inflamm Bowel Dis. 2008;14:1298 1312.
   
   
7. Wyant T, Fedyk E, Abhyankar B. J Crohns Colitis. 2016;10(12):1437-1444.
   
   
8. Baumgart DC, Carding SR. Lancet. 2007;369:1627-1640.
   
   
9. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Lancet. 2017; 389(10080):1741-1755.
   
   
10. Krugliak N, Torres J, Rubin DT. Gastroenterology. 2022;162:1396-1408.
    
    
11. Ordas I, Eckmann L, Talamini M, et al. Lancet. 2012;380:1606-1619.
    
    
12. Feuerstein JD, Cheifetz AS. Mayo Clin Proc. 2017;92:1088-1103.
    
    
13. Sands BE. Gastroenterology. 2004;126:1518-1532.
    
    
14. Kobayashi T, Siegmund B, Le Berre C, et al. Nat Rev Dis Primers. 2020;6(74).
    
    

SOURCE: Takeda Pharmaceutical Co