近日，严重哮喘的生物技术新药Nucala (mepolizumab，美泊利单抗)获欧盟的批准，这是全球首个也是唯一一个靶向白细胞介素-5(IL-5)的单抗，用于治疗重度嗜酸性粒细胞性哮喘。
批准日期：2015年11月4日[美国及欧盟]  2016年3月30日[日本] 公司：葛兰素史克
注射用NUCALA(美泊利单抗[mepolizumab])，为皮下使用
初次批准：2015
作用机制
美泊利单抗是一个白介素-5拮抗剂(IgG1 kappa)。IL-5是负责嗜酸性的生长和分化，招募，激活，和生存的主要细胞因子. 美泊利单抗结合至IL-5有一个解离常数100 pM，抑制IL-5的生物活性通过阻断其与表达在嗜酸性细胞表面的IL-5受体复合物α链的结合。哮喘的发病机理中炎症是一个重要组分。在炎症中涉及多种细胞类型(如，肥大细胞，嗜酸性，嗜中性，巨噬细胞，淋巴细胞)和介质(如，组织胺，花生酸类，白三烯类，细胞因子)。美泊利单抗，通过抑制IL-5信号，减低嗜酸性的产生和生存；但是，尚未确定性地确定美泊利单抗在哮喘中作用。
适应证和用途
NUCALA是一种白介素-5拮抗剂单克隆抗体(IgG1 kappa)适用为有严重哮喘年龄12岁和以上，和有一个嗜酸性表型患者的添加维持治疗。
使用限制：
⑴ 不为其他嗜酸性情况的治疗。
⑵  不为急性支气管痉挛或哮喘状态的缓解。
剂量和给药方法
100mg皮下给药每四周1次。
对冰冻干燥粉重建，和注射的制备和给药的指导见完整处方资料。
剂型和规格
注射用：为重建100mg冰冻干燥粉在单剂量小瓶中。
禁忌证
对制剂中美泊利单抗或赋形剂超敏性史。
警告和注意事项
⑴NUCALA的给药后曽发生超敏性反应(如，血管水肿，支气管痉挛，高血压，荨麻疹，皮疹)。在超敏性反应的事件中终止NUCALA。
⑶ 不要使用治疗急性支气管痉挛或哮喘状态。
⑶接受NUCALA患者中曽发生带状疱疹感染。用NUCALA开始治疗前如医疗上适当考虑水痘疫苗接种。
⑷在用NUCALA开始治疗时不要突然终止全身或吸入皮质激素。如适当逐渐减低皮质激素。
⑸用NUCALA治疗前治疗有预先存在蠕虫感染的患者。如当接受用NUCALA治疗患者成为被感染时和对抗蠕虫治疗没有反应，终止NUCALA直至寄生虫感染解决。
不良反应
最常见不良反应(发生率大于或等于5%)包括头痛，注射部位反应，背痛，和疲乏。
包装规格[德国上市包装]
100mgx1瓶
100mgx3瓶

Nucala (Mepolizumab)：EMA OKs Nucala for Severe Refractory Eosinophilic Asthma
The European Medicines Agency (EMA) has approved mepolizumab (Nucala, GlaxoSmithKline) as an add-on treatment for severe refractory eosinophilic asthma in adults in the 31 European countries covered by the EMA, according to a company statement.
Mepolizumab will be the first anti-interleukin-5 (IL-5) treatment for these patients in the European Union. IL-5 is important in regulating eosinophil regulation in patients with asthma. Mepolizumab is given as a subcutaneous injection of 100 mg every 4 weeks in addition to the patient's usual respiratory medications, which often include high-dose inhaled corticosteroids and additional medicines that may include oral corticosteroids.
Approximately 242 million individuals worldwide live with asthma. Existing therapies provide relief for many of these patients, but fewer than 5% of patients have severe refractory treatment that is not controlled with existing treatments.
Severe asthma requires medication with high-dose inhaled corticosteroids and the addition of a second controller (and/or systemic corticosteroids) to prevent the asthma from becoming uncontrolled or remaining uncontrolled despite the use of these medications. These patients may need long-term oral corticosteroids.
In severe eosinophilic asthma, the overproduction of eosinophils causes lung inflammation that can affect the airways, restricting respiration and increasing the frequency of asthma attacks.
IL-5 is the main stimulator of eosinophilic growth, activation, and survival, and promotes eosinophil movement from the bone marrow into the lung. As many as 60% of those with severe asthma have eosinophilic airway inflammation.
Mepolizumab is a monoclonal antibody that prevents IL-5 from binding to its receptor on the surface of eosinophils. This binding reduces eosinophil levels in the blood, tissue, and sputum.
"Not the Typical 'Asthma' Patients"
"Patients with severe refractory eosinophilic asthma are not the typical 'asthma' patients many people are familiar with. Despite taking high doses of inhaled medications, they struggle to control their asthma," lead investigator of the first proof-of-concept trial for mepolizumab and an investigator for the phase 3 MENSA study, Professor Ian Pavord, DM, FRCP, from the University of Oxford, commented in the news release.
"They have particular problems with frequent asthma attacks and can require hospitalisation. Many also take oral corticosteroids to control their symptoms, which we know can lead to side effects that patients often find very difficult to deal with. To be able to offer these patients a treatment that specifically targets the underlying cause of their disease will be an important option," he said.
The phase 2 and phase 3 trials included nine studies with a total of 915 participants with severe refractory eosinophilic asthma who were given either a subcutaneous or an intravenous dose of mepolizumab during clinical trials lasting 24 to 52 weeks. Those three clinical trials (DREAM [MEA112997], MENSA [MEA115588], and SIRIUS [MEA115575]) found mepolizumab to be efficacious and safe for those patients with severe refractory eosinophilic asthma.
The trials studied the efficacy and safety of mepolizumab in those with severe asthma. All participants in the MENSA and SIRIUS studies had eosinophil levels in their peripheral blood of at least 150 cells/μL at the beginning of treatment, or at least 300 cells/μL in the previous year.
A summary of product characteristics is available on the European Commission's website.
The US Food and Drug Administration approved Nucala on November 4, 2015, as an add-on treatment for patients aged 12 years and older with severe eosinophilic asthma.
Other countries, including Japan, have submitted regulatory applications that are under review.
Mepolizumab is contraindicated in those with hypersensitivity to mepolizumab or any of its excipients. It should not be used for treatment of acute asthma exacerbations.
Adverse events usually occur within hours of admission, but can be delayed. They include acute and delayed systemic reactions, including hypersensitivity reactions (eg, urticaria, angioedema, rash, bronchospasm, and hypotension). Patients who experience any of these events or whose asthma worsens or remains uncontrolled after beginning treatment should seek medical advice.
The most frequent reported events in the clinical studies of patients with severe refractory eosinophilic asthma were headache, injection site reactions, and back pain. Headaches were very common, occurring in at least one of every 10 patients. Other common adverse events included lower respiratory tract infection, urinary tract infection, pharyngitis, hypersensitivity reactions (systemic, allergic), nasal congestion, upper abdominal pain, eczema, back pain, administration-related reaction (systemic, nonallergic), local injection site reactions, and pyrexia.
Do not discontinue mepolizumab or corticosteroids abruptly; discontinuing or reducing corticosteroids should be gradual and occur only under the supervision of a physician.
http://www.medicines.org.uk/emc/medicine/31388