武田在美国推出单抗新药Entyvio

武田（Tkeda）6月17日宣布，在美国推出单抗药物Entyvio（vedolizumab），该药于2014年5月获FDA和欧盟批准，用于中度至重度活动性溃疡性结肠炎（ulcerative colitis，UC）和克罗恩病（Crohn's disease，CD）成人患者的治疗。

Vedolizumab生物制品许可申请（BLA）和上市许可申请（MAA）的提交，是根据GEMINI项目的汇总数据，该项目包括4个III期研究，这是迄今为止在CD和UC患者中开展的最大的III期临床试验项目，旨在评估vedolizumab用于治疗既往至少经一种常规治疗或TNF-α拮抗剂治疗失败的中度至重度活动性克罗恩病和溃疡性结肠炎患者时，对临床反应、临床缓解、长期安全性的影响。

Vedolizumab是一种全人源化单克隆抗体，特异性拮抗α4β7整合素，抑制α4β7整合素对肠道黏膜细胞粘附分子MAdCAM-1的结合。MAdCAM-1选择性表达于肠胃血管和淋巴结。α4β7整合素表达于一组循环（circulating）白细胞，这些细胞已被证明在CD和UC疾病中介导炎症过程中发挥了重要作用。

英文原文：ENTYVIOTM (vedolizumab) Now Available in the United States for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis and Crohn's Disease

Deerfield, Ill., June 16th, 2014, and Osaka, Japan, June 17th, 2014 – Takeda Pharmaceutical Company Limited (“Takeda”) and its wholly-owned subsidiary, Takeda Pharmaceuticals U.S.A., Inc., today announced the United States (U.S.) commercial availability of a new biologic therapy, ENTYVIOTM (vedolizumab), for the treatment of adults with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD).1

“We understand how a great need still exists for additional treatment options for ulcerative colitis and Crohn’s disease patients,” said Nicole Mowad-Nassar, vice president, marketing, Takeda Pharmaceuticals, U.S.A., Inc. “We’re pleased that we were able to make Entyvio available for appropriate patients so quickly after receiving FDA approval.”

In May, the U.S. Food and Drug Administration (FDA) simultaneously approved Entyvio for the treatment of adults with moderately to severely active UC and CD. That same month, Entyvio was also granted Marketing Authorisation in the European Union from the European Commission (EC) for the treatment of adults with moderately to severely active UC and CD.1,2

Entyvio is now available to U.S. healthcare providers for inducing and maintaining clinical response and remission, improving endoscopic appearance of the mucosa, and achieving corticosteroid-free remission in adult patients with moderately to severely active UC 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. Entyvio is also indicated for achieving clinical response and remission, and achieving corticosteroid-free remission 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.1

In order to connect patients in need with access and services for Entyvio, Takeda has launched EntyvioConnect, with dedicated case managers available to answer questions. For more information, visit www.ENTYVIO.com/hub/.

About ENTYVIO® (vedolizumab)
Entyvio, an integrin receptor antagonist, is a humanized monoclonal antibody that specifically binds to the alpha4beta7 integrin and blocks the interaction of alpha4beta7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. Entyvio does not bind to or inhibit function of the alpha4beta1 and alpha E beta 7 integrins and does not antagonize the interaction of alpha4 integrins with vascular cell adhesion molecule-1 (VCAM-1). The alpha4beta7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the gastrointestinal tract. MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T-lymphocytes to gut lymph tissue. The interaction of the alpha4beta7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease.1

INDICATIONS: ENTYVIO® (vedolizumab)

Adult Ulcerative Colitis (UC)
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:
• inducing and maintaining clinical response
• inducing and maintaining clinical remission
• improving endoscopic appearance of the mucosa
• achieving corticosteroid-free remission

Adult Crohn's Disease (CD)
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:
• achieving clinical response
• achieving clinical remission
• achieving corticosteroid-free remission

IMPORTANT SAFETY INFORMATION

• ENTYVIO (vedolizumab) is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.

• Infusion-related reactions and hypersensitivity reactions including anaphylaxis have occurred. If anaphylaxis or other serious allergic reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.

• Patients treated with ENTYVIO are at increased risk for developing infections. Serious infections have been reported in patients treated with ENTYVIO. ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding ENTYVIO in patients who develop a severe infection while on treatment with ENTYVIO. Exercise caution in patients with a history of recurring severe infections.

• Although no cases of PML have been observed in ENTYVIO clinical trials, JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death has occurred in patients treated with another integrin receptor antagonist. A risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms. If PML is suspected, withhold dosing with ENTYVIO and refer to a neurologist; if confirmed, discontinue ENTYVIO dosing permanently.

• There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury.

• Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines. Patients receiving ENTYVIO may receive non-live vaccines and may receive live vaccines if the benefits outweigh the risks.

• Most common adverse reactions (incidence greater than or equal to 3% and greater than or equal to 1% higher than placebo): nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.