武田（Takeda）5月20日宣布，单抗药物Entyvio（vedolizumab）获FDA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。FDA于2013年9月曾授予vedolizumab优先审查资格。

此外，vedolizumab于2014年3月获得了欧洲药品管理局（EMA）人用医药产品委员会（CHMP）建议批准的积极意见。

Vedolizumab生物制品许可申请（BLA）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：

FDA Approves Takeda's Entyvio? (vedolizumab) for the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis or Crohn's Disease

he U.S. Food and Drug Administration today approved Entyvio (vedolizumab) injection to treat adult patients with moderate to severe ulcerative colitis and adult patients with moderate to severe Crohn's disease.

Entyvio is approved to treat those conditions when one or more standard therapies (corticosteroids, immunomodulators, or tumor necrosis factor blocker medications) have not resulted in an adequate response.

Ulcerative colitis is a chronic disease that affects about 620,000 Americans. It causes inflammation and ulcers in the inner lining of the large intestine and is one of two main forms of chronic inflammatory bowel disease. The inflammation can lead to abdominal discomfort, gastrointestinal bleeding, and diarrhea.

Crohn's disease is a chronic inflammatory condition that causes inflammation, or swelling, and irritation of any part of the digestive tract—also called the gastrointestinal (GI) tract. More than a half million Americans have been diagnosed with Crohn's disease.

"Ulcerative colitis and Crohn's disease are debilitating diseases that impact the quality of life of those who have these conditions," said Amy G. Egan, M.D., M.P.H., acting deputy director of the Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research. "Although there is no cure for these conditions, today's approval provides an important new treatment option for patients who have had an inadequate response to conventional therapy to help control their symptoms."

The safety and effectiveness of Entyvio for ulcerative colitis were established in two clinical trials involving approximately 900 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. Evaluations of patients included measures of stool frequency, rectal bleeding, endoscopic findings and a physician's overall assessment.

Results showed that a greater percentage of participants treated with Entyvio compared to a placebo achieved and maintained clinical response, achieved and maintained clinical remission, achieved corticosteroid-free clinical remission, and as seen during endoscopy, had improved appearance of the colon.

The safety and effectiveness of Entyvio for Crohn's disease were established in three clinical trials involving approximately 1,500 patients who had not responded adequately to corticosteroids, immunomodulators, or tumor necrosis factor blocker medications. Results showed that a greater percentage of participants treated with Entyvio compared to a placebo achieved clinical response, achieved clinical remission, and achieved corticosteroid-free clinical remission.

Entyvio is an integrin receptor antagonist. Integrin receptors are proteins expressed on the surface of certain cells. Integrin receptors function as bridges for cell-cell interactions. Entyvio blocks the interaction of a specific integrin receptor (expressed on circulating inflammatory cells) with a specific protein (expressed on cells in the interior wall of blood vessels), and thereby blocks the migration of those circulating inflammatory cells across those blood vessels and into areas of inflammation in the gastrointestinal tract. The most common side effects in patients treated with Entyvio include headache, joint pain, nausea, and fever. The most serious risks associated with Entyvio include serious infections, hypersensitivity and infusion-related reactions; and hepatotoxicity.

Another type of integrin receptor antagonist has been associated with progressive multifocal leukoencephalopathy (PML), a rare and often fatal opportunistic infection of the central nervous system. PML is caused by a virus and typically only occurs in patients whose immune systems are compromised. There were no cases of PML identified among Entyvio clinical trial participants.

In Entyvio clinical trials, participants were actively monitored for PML with frequent and regular screenings, and evaluations of any new, unexplained neurological symptoms, as necessary. Because clinical trials are conducted under tightly controlled conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates that might be observed in practice. Therefore, while there were no cases of PML seen among patients participating in Entyvio clinical trials, there remains uncertainty regarding the risk of PML in patients taking Entyvio.

Health care professionals should monitor patients on Entyvio for any new onset, or worsening, of neurological signs and symptoms. The FDA will continue to work with the sponsor to further investigate the risk of PML through a required post-marketing study and enhanced, expedited adverse event reporting.