英文药名：Olumiant（Baricitinib Tablets）

中文药名：巴瑞克替尼薄膜衣片

生产厂家：礼来日本有限公司

オルミエント錠4mg／オルミエント錠2mg

药物分类名称
Janus激酶（JAK）抑制剂
批准日期：2017年2月
商標名
Olumiant
一般名：
バリシチニブ（JAN）
Baricitinib
化学名：
｛1-（Ethylsulfonyl）-3-［4-（7H-pyrrolo［2,3-d］pyrimidin-4-yl）-1H-pyrazol-1-yl］azetidin-3-yl｝acetonitrile
分子式：
C16H17N7O2S
分子量：
371.42
構造式：

性　状：
它是一种白色的粉末。
易溶于二甲基亚砜，难溶于乙腈和甲醇，极不溶于乙醇（99.5），难溶于水。
熔点：
约213°C
批准条件
1.制定药品风险管理计划，适当实施。
2.制造和销售后，通过对所有案件进行使用结果调查，早日收集该药物的安全性和有效性数据，直到有一定数量的病例数据累积 并采取必要措施正确使用该药。
药效药理
1. 作用机序
当涉及造血，炎症和免疫功能的各种细胞因子和生长因子与受体结合时，进行由JAK介导的细胞内信号转导。 在细胞内信号通路中，JAK自身磷酸化，相应的信号转导和转录激活因子（STAT）被磷酸化。 磷酸化的STAT迁移到核中并增强对细胞因子的响应的基因的转录。
Varicitinib抑制JAK1和JAK2活性，通过抑制STAT的磷酸化和激活来抑制信号传导。
2. JAK抑制活性
Valicitinib是JAK1/JAK2的选择性和可逆抑制剂，在酶抑制试验中抑制JAK1，JAK2，TYK2和JAK3活性，其抑制作用的IC50分别为5.9,5.7,53和> 400nM。
3. 由IL-6诱导的STAT3磷酸化的抑制作用
在使用健康志愿者的全血给药的健康受试者的测定中，IL-6诱导的STAT3磷酸化的剂量依赖性抑制。 抑制作用在给予Valicitinib后2小时最大，STAT3磷酸化水平在24小时后几乎恢复到基线。 当用IL-6（通过JAK1/JAK2信号传导）或血小板生成素（通过JAK2 / JAK2发信号）刺激时，观察到类似的抑制作用。
适应病症
类风湿关节炎（包括预防关节结构损伤）在现有治疗中效果不佳。
用法与用量
成人；对于采用日剂量4mg治疗的患者，如病情已取得持续控制，可将日剂量改为2mg
包装规格
片剂
2mg：30片PTP（5×6片）

4mg：30片PTP（5×6片）

制造厂商
礼来日本有限公司
完整说明书附件：http://www.info.pmda.go.jp/go/pack/3999043F1020_1_02/
Selective JAK 1/JAK 2 inhibitor "Ormiento (R) tablet 4 mg, same 2 mg" Acquired manufacturing and marketing approval in Japan for indications of rheumatoid arthritis inadequate in existing treatment。
Eli Lilly Japan Ltd.
Japan Eli Lilly Co., Ltd. (Headquarters: Hyogo Prefecture Kobe City, President: Patrick Johnson, hereinafter "Eli Lilly Japan") is a selective JAK1 / JAK2 inhibitor "Ormiento (R) tablets 4 mg, same 2 mg" Name: Balicitinib, hereinafter referred to as "Ormiento (R)"), from the Ministry of Health, Labor and Welfare on this date, approval of manufacture and marketing as "indication of rheumatoid arthritis insufficiently effective in existing treatment (including prevention of structural damage of joints) We have announced that we have acquired.
Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation and progressive damage i, ii. The number of patients in Japan is estimated to be 70 to 800 thousand people iii, and females are three times more likely than men iv. Rheumatoid arthritis is a disease that places a heavy burden on patients such as lowering of physical function, lowering of labor ability and difficulty in daily life. In recent years, the treatment of rheumatoid arthritis has developed greatly, and with the advent of conventional anti-rheumatic drugs and biologics, which is the current standard therapy, we aim to "remission" and "low disease activity", through the suppression of joint destruction It was an era where patients' long-term prognosis could be improved. However, there are still many patients who are not satisfying important needs to improve the quality of life (QOL), such as improvement of subjective symptoms such as pain, fatigue and morning stiffness.
Ormiento (R) is a selective JAK1/JAK2 inhibitor for oral administration once a day. The effectiveness and safety of Ormiento (R) in combination with monotherapy or methotrexate was confirmed in the first and second trials including 4 completed completed trials of 2,890 rheumatoid patients with various treatment history including 371 Japanese It was confirmed in phase III clinical trials. In the RA-BEAM test, comparison between this drug and adalimumab (TNF inhibitor) under methotrexate use was prescribed and carried out. This drug has the same effect as that of adalimumab for the disease activity and the inhibitory effect on joint destruction in patients who were ineffective for treatment with methotrexate, which is the current standard therapy, and the patient's pain We also improved the PRO (Patient Report Outcome)
* evaluating subjective symptoms such as fatigue and morning stiffness from 1 week after administration.
In addition, in adverse analysis (Phase II and Phase III study) of domestic and overseas clinical trials, adverse events that did not deny a causal relationship with this drug in 3,439 total cases to which Ormiento (R) was administered are , And 1,428 cases (41.5%). Main events include upper respiratory tract infection, shingles etc.
was. Major clinical laboratory abnormalities were LDL cholesterol elevation etc.
At the time of this approval, Belkra Pierre Eve, head of the biopharmaceutical field headquarters of R & D headquarters in Eli Lilly Japan, said, "The acquisition of Ormiento (R) manufacturing and marketing approval is a very meaningful step for Japan's Eli Lilly, and all employees, Oliento (R), as the next generation of therapeutic drugs, are being treated by rheumatoid arthritis patients We sincerely wish to satisfy the needs of patients with rheumatoid arthritis and medical professionals in Japan and to greatly improve rheumatoid arthritis medicine through not only suppressing joint destruction but also improving subjective symptoms in daily life. "
* Patient-reported outcome (PRO: Patient-reported outcome) means "any report on the health condition (symptoms, satisfaction, etc.) of patients directly obtained from patients without intervention by clinician or someone else" I will point it. (See FDA 2009 guidelines)
Outline of content of manufacturing and sales approval
Sales name Ormient (R) tablets 4 mg, same 2 mg
Common name Balicitinib
Manufacturing marketing authorization acquisition date July 3, 2017
Indications and efficacies Rheumatoid arthritis insufficiently effective in existing treatment (including prevention of structural damage of joints)
[Usage Precautions Related to Indications / Effects]
In past treatments, at least one drug, including methotrexate
Even if appropriate treatment with anti-rheumatic medicine or the like is carried out, obvious
If symptoms persist, administer it.
Dosage/dosage Usually, adults receive 4 mg of valicitinib once daily orally.
In addition, it should be reduced to 2 mg according to the condition of the patient.
About Ormiento (R)
Ormiento (R) is a selective JAK1 and JAK2 inhibitor once daily orally administered, and clinical trials are currently being conducted for inflammatory diseases and autoimmune diseases. Four kinds of JAK enzymes, JAK 1, JAK 2, JAK 3, and TYK 2 are known. JAK-dependent cytokines are associated with the pathogenesis of many inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be beneficial in the treatment of diseases with a wide range of inflammatory conditions including rheumatoid arthritis It will be.
In December 2009, Lilly and Insight Corporation (hereinafter Insight) is a global exclusive company for the development and commercialization of valicitinib and certain subsequent compounds for the treatment of inflammatory and autoimmune diseases We announced that we have agreed to license and collaborative research. In the first quarter of 2016, an application for approval of the marketing of Varicitinib that adapted rheumatoid arthritis was made to the regulatory authorities of the United States, the European Union, and Japan. Manufacture and sale of Olientient (R) was approved in Europe in February 2017. In April 2017, the US Food and Drug Administration (FDA) issued a Complete Response Letter to Oliento (R) New Drug Registration Application (NDA). In June 2017 Switzerland and Kuwait, in July 2017 in Japan, manufacture and sale of Oliento (R) was approved as a treatment for rheumatoid arthritis.
About rheumatoid arthritis
Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and progressive injury i, ii. Over 23 million people worldwide suffer from rheumatoid arthritis v. The number of patients is about three times higher in females than in males v. Current treatments for rheumatoid arthritis are thought to be related to the pathogenesis of nonsteroidal anti-inflammatory drugs, oral conventional disease modifying anti-rheumatic drugs (cDMARDs) such as current standard therapy methotrexate, and rheumatoid arthritis There are biological disease modifying anti-rheumatic drugs (bDMARDs) which are injections targeting selective mediators being vi vi. Despite the current treatment options, many patients do not achieve therapeutic goals or sustained remission vii. There is still an important need for new treatments that will improve patient overall care.
About Phase III clinical trial of Balicitinib
Lilly and Insight conducted four Phase III clinical trials on valicitinib for patients with moderate to advanced disease-active rheumatoid arthritis for filing for regulatory approval in many countries. In two clinical trials out of four clinical trials, comparison with previously approved disease-modifying anti-rheumatic drug (DMARD) (comparison with methotrexate in RA-BEGIN test and adalimumab in RA-BEAM test and ) In order to compare with each other. An additional Phase III clinical trial has been added for clinical development in China. The clinical trial program includes the use of methotrexate unused, insufficient methotrexate effect, insufficient effect of conventional synthetic disease modifying antirheumatic drug (csDMARD) effect, or biological disease modifying antirheumatic drug (bDMARDs) including TNF inhibitor A wide range of patients with insufficient effect are incorporated. Patients who have completed either Phase III clinical trial can be enrolled in a long-term continuous dose study. For more information on the clinical trial program, please visit www.clinicaltrials.gov.
About Insight Corporation
Insight is a biopharmaceutical company based in Wilmington, Delaware, with an emphasis on discovery, development and commercialization of generic drugs. For details on insight, please visit www.incyte.com.
About Eli Lilly & Company
Eli Lilly is a global leader in healthcare linking care and drug discovery to make people's lives worldwide better. Eli Lilly Company was founded by a single man who has devoted all his efforts to the creation of high quality medicines that meet the true needs more than a century ago and continues to remain loyal to its mission in all businesses today It is. Eli Lilly's employees around the world develop and deliver drugs that change the lives of people who need it, improve understanding and management of diseases, and through regional activities and charity activities I am working to return profits to society.
About Japan Eli Lilly
Japan Eli Lilly Co., Ltd. is a Japanese subsidiary of Eli Lilly & Company, USA. Through developing, manufacturing, importing, and selling innovative medicines, people can realize longer, healthier and more fulfilling lives by promoting cancer, diabetes, musculoskeletal diseases, central nervous system diseases, autoimmune diseases, It contributes to medical treatment in Japan in areas such as growth disorders, pain and so on.
For details, please visit our website.