Lexington, Mass. and Osaka, Japan, December 20, 2019 – Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that it has received a Complete Response Letter from the U.S. Food and Drug Administration (FDA) in response to the submission of a Biologics License Application (BLA) for the approval of an investigational subcutaneous formulation of Entyvio® (vedolizumab) for maintenance therapy in adults with moderate to severe ulcerative colitis (UC).
Takeda is assessing the details of the letter, gathering information needed to resolve the FDA’s questions, and will work closely with the FDA on a path to approval. In its letter, the FDA posed questions unrelated to the clinical data and conclusions from the pivotal trial supporting the BLA.
Takeda strongly believes in the potential benefit that subcutaneous Entyvio can bring to patients who live with moderate to severe UC. The company remains committed to working with the FDA to meet patient needs with this important route of administration.
Since intravenous (IV) Entyvio was approved by the U.S. FDA in 2014 for patients with moderate to severe UC and Crohn’s disease, clinical trials and other evidence have continued to support its well-established safety and efficacy profile.[i],[iii] Entyvio IV has been granted marketing authorization in more than 60 countries, including the U.S. and European Union; in the U.S. more than 150,000 patients have used Entyvio.[i],[ii]
“At Takeda, we know how important it is to provide physicians and patients with choices, and we continue to drive innovation and development to meet their needs,” said Asit Parikh, MD, PhD, head of Takeda’s Gastroenterology Therapeutic Area Unit. “We’re committed to the development of the subcutaneous formulation of Entyvio, and look forward to working closely with the FDA to determine next steps.”
Ulcerative colitis (UC) and Crohn’s disease (CD) are two of the most common forms of inflammatory bowel disease (IBD).[iv] Both UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal tract that are often progressive in nature.[v],[vi] UC only involves the large intestine as opposed to CD which can affect any part of the GI tract from mouth to anus.[vii],[viii] CD can also affect the entire thickness of the bowel wall, while UC only involves the innermost lining of the large intestine.[vi],[vii] UC commonly presents with symptoms of abdominal discomfort, loose bowel movements, including blood or pus.[vii],[ix] CD commonly presents with symptoms of abdominal pain, diarrhea, and weight loss.[v] The cause of UC or CD is not fully understood; however, recent research suggests heredity, genetics, environmental factors, and/or an abnormal immune response to microbial antigens in genetically predisposed individuals can lead to UC or CD.[vii],[x],[xi]
Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation.[ii] It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal address in cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1).[xii] MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.[xiii] The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.[xii] These cells have been shown to play a role in mediating the inflammatory process in UC and CD.[xii],[xiv],[xv] By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.[xii]
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.[ii]
U.S. INDICATIONS: ENTYVIO (vedolizumab) FOR INTRAVENOUS USE
Adult Ulcerative Colitis (UC)
ENTYVIO (vedolizumab) is indicated in adult patients with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids for inducing and maintaining clinical response, inducing and maintaining clinical remission, improving endoscopic appearance of the mucosa, and achieving corticosteroid-free remission.
Adult Crohn’s Disease (CD)
ENTYVIO (vedolizumab) is indicated in adult patients with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids for achieving clinical response, achieving clinical remission, and achieving corticosteroid-free remission.
U.S. IMPORTANT SAFETY INFORMATION FOR ENTYVIO (VEDOLIZUMAB) FOR INTRAVENOUS USE
More information is available in the U.S. at www.ENTYVIOHCP.com.
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 more than 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, short bowel syndrome, 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.
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.
Takeda has maintained a strong and growing commitment to the United States for more than 50 years. On January 8, 2019, Takeda completed its acquisition of Shire, PLC, becoming a global, values-based, R&D-driven biopharmaceutical leader. In the U.S., Takeda employs more than 18,000 employees across multiple business units, and as of August 2019, is headquartered out of the greater Boston area.
Additionally, Takeda also has a research facility in San Diego, California, specialty products manufacturing facilities in Brooklyn Park, Minnesota and plasma fractionation manufacturing facilities in Covington, Georgia.
As one of the world’s leading biopharmaceutical companies, Takeda is committed to bringing Better Health and a Brighter Future to people worldwide. We aspire to bring our leadership in translating science into life-changing medicines to the next level, in our core focus areas; oncology, gastroenterology, neuroscience, rare diseases, plasma-derived therapies, and vaccines.
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[i] Data on file. Takeda Pharmaceuticals.
[ii] Entyvio (vedolizumab) prescribing information. Takeda Pharmaceuticals.
[iii] Narula N, Peerani F, Meserve J, et al. Am J Gastroenterol. 2018;113:1345-1354.
[iv] Baumgart DC, Carding SR. Lancet. 2007;369:1627-1640.
[v] Baumgart DC, Sandborn WJ. Lancet. 2012;380:1590-1605.
[vi] Torres J, Billioud V, Sachar DB, et al. Inflamm Bowel Dis. 2012;18:1356-1363.
[vii] Ordas I, Eckmann L, Talamini M, et al. Lancet. 2012;380:1606-1619.
[viii] Feuerstein JD, Cheifetz AS. Mayo Clin Proc. 2017;92:1088-1103.
[ix] Sands BE. Gastroenterology. 2004;126:1518-1532.
[x] Henckaerts L, Pierik M, Joossens M, et al. Gut. 2007;56:1536-1542.
[xi] Kaser A, Zeissig S, Blumberg RS. Dig Dis. 2010;28:395-405.
[xii] Soler D, Chapman T, Yang LL, et al. J Pharmacol Exp Ther. 2009;330:864-875.
[xiii] Briskin M, Winsor-Hines D, Shyjan A, et al. Am J Pathol. 1997;151:97-110.
[xiv] Eksteen B, Liaskou E, Adams DH. Inflamm Bowel Dis. 2008;14:1298‑1312.
[xv] Wyant T, Fedyk E, Abhyankar B. J Crohns Colitis. 2016;10:1437-1444.