2015年11月4日,美国食品和药品监管局(FDA)批准Nucala (美泊利单抗[mepolizumab])在年龄12岁和以上患者与其他哮喘药物使用为维持哮喘治疗。Nucala是被批准为尽管接受他们的当前哮喘药物有严重哮喘发作(加重)病史的患者。
哮喘是一种慢性病致肺气道中炎症。一个哮喘发作期间，气道变得狭窄使之难以呼吸。严重哮喘发作可导致哮喘-相关住院因为这些发作可能是严重和甚至威胁生命。根据美国疾病控制和预防中心，如2013年，在美国超过22百万人有哮喘，和每年哮喘-相关住院超过400,000。
FDA的药品评价和研究中心中肺，过敏，和风湿病产品部主任Badrul Chowdhury，M.D.，Ph.D说：“这个批准提供有严重哮喘患者当当前治疗不能维持他们的哮喘适当控制时一个另外治疗，”。
Nucala是由卫生保健专业人员每四周通过皮下注射给药至上臂，腿，或腹部。Nucala是一种人源化白介素-5拮抗剂单克隆抗体，通过重组DNA技术在中国仓鼠卵巢细胞中生产。Nucala通过减低血液嗜酸性-水平减低严重哮喘发作，嗜酸性是一种类型白血细胞对哮喘的发展有贡献。
在三项双盲，随机化，安慰剂对照试验在有严重哮喘用当前地可得到治疗患者确定Nucala的安全性和疗效。Nucala或一种安慰剂被给予患者每四周作为一种添加哮喘治疗。与安慰剂比较，有严重哮喘接受Nucala患者有较低加重需要住院和/或急诊就诊，和至首次加重较长时间。此外，有严重哮喘接受Nucala患者同时维持哮喘控制与接受安慰剂患者比较，他们的每天口服皮质激素维持剂量经历较大减低。当用患者在一秒钟呼出空气体积测定用美泊利单抗治疗不导致肺功能限制改善。
Nucala的最常见副作用包括头痛，注射部位反应(疼痛，发红，肿胀，痒，或在注射部位一种烧灼感觉)，背痛，和虚弱(疲乏)。正在用Nucala治疗在几小时或几天可能发生超敏性反应，包括面，口，和舌肿胀；昏晕，眩晕，或头轻脚重；荨麻疹；呼吸问题和皮疹。接受Nucala患者曾发生带状疱疹感染。带状疱疹感染是引起带状疱疹病毒。
Nucala是由北卡罗来纳在三角研究园GlaxoSmithKline公司制造。
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471031.htm
New Drugs Online Report for mepolizumab
Information
Generic Name: mepolizumab  
Trade Name: Nucala 
Synonym: SB240563 
Entry Type: New molecular entity  
Development and Regulatory status
UK: Recommended for approval (Positive opinion) 
EU: Recommended for approval (Positive opinion) 
US: Recommended for approval (Positive opinion) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Sep 15: EU positive opinion for use as an add-on treatment for severe refractory eosinophilic asthma in adults [14].
25/09/2015 10:54:54 
Jun 15: An FDA Advisory Committee vote 14-0 that efficacy and safety data for mepolizumab support the drug’s approval in adults. The panel also voted that efficacy data provide substantial evidence of a clinically meaningful benefit in this population (14-0) and that safety in adults with severe asthma had been adequately demonstrated (13-1). Use in adolescents 12-17 years of age with severe asthma was not supported (4-10). It concluded that efficacy (5 yes, 9 no) and safety (2-12) had not been adequately shown mostly because of the limited number of patients included, and said further data are needed in this sub-population where there is a high unmet need [13].
12/06/2015 12:14:09 
Nov 14: Filed in US and EU [11].
07/11/2014 15:46:10 
Mar 14: GSK plan to start global filings at the end of 2014 [8].
13/03/2014 12:07:54 
Oct 12: PIII programme starts [3].
30/10/2012 08:43:06 
Aug 12: PIII development planned before end of 2012 [2].
17/08/2012 19:53:32 
Trial or other data
Analysts believe IL-5 products, which also includes Teva’s soon-to-be-filed reslizumab, could expand the asthma market by billions of dollars [13].
28/09/2015 14:46:56
Sep 14: Pivotal PIII study published in NEJM. In patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high-dose inhaled corticosteroids, both IV (75mg) and subcutaneous (100mg) mepolizumab (given every 4 weeks) reduced exacerbation rate vs. placebo (by 47% and 53%, respectively) [10].
10/09/2014 12:16:01
Mar 14: The pivotal PIII study (MEA115588) met its primary endpoint. The study evaluated f two dose regimens of mepolizumab vs placebo, 75mg IV and 100mg SC, every 4 weeks. Patients remained on their current asthma maintenance therapy. For the primary end point, both mepolizumab treatment arms showed statistically significant reductions in the frequency of clinically significant exacerbations of asthma vs placebo (75mg IV, 47%, p<0.001; 100mg SC, 53%, p<0.001). Adverse events were similar across all treatment groups. The most common were nasopharyngitis, headache, upper respiratory tract infection and asthma. The frequency of AEs was 83% in the placebo group, 84% in the mepolizumab 75mg IV and 78% in the mepolizumab 100mg SC group. The frequency of serious adverse events was 14%, 7% and 8% respectively. A second PIII study (MEA115575) of mepolizumab 100mg SC, every 4 weeks vs placebo also reported positive results. Patients on mepolizumab achieved greater reductions in their maintenance oral corticosteroid dose during weeks 20-24 vs placebo (p =0.008), while maintaining asthma control [9].
16/03/2014 17:58:27
Oct 12: NCT01691508: MEA115575: A randomised, double-blind, placebo-controlled, multicentre study of mepolizumab adjunctive therapy to reduce steroid use in 120 subjects with severe refractory asthma. The primary outcome is % reduction of oral corticosteroid dose during weeks 20 to 24 vs baseline while maintaining asthma control. Mepolizumab will be given as a 100mg sc dose every 4 weeks. Inclusion criteria include: regular treatment with maintenance systemic corticosteroids over ≥6mo and a stable oral dose for 4 weeks prior to visit 1 (≡ 5-35mg/day prednisone); regular treatment with high dose inhaled corticosteroid over ≥6mo ≡ ≥ 880mcg/day fluticasone propionate (FP); current treatment with an additional controller medication for ≥3months OR has used and failed an additional controller medication for ≥3 successive months during the prior 12mo [LABA, leukotriene receptor antagonist or theophylline]; eosinophilic asthma; pre-bronchodilator FEV1 <80% predicted. The study starts Oct 12 and is due to complete Apr 14 [4].
30/10/2012 09:09:32
NCT01691521: MEA115588 A randomised, double-blind, double-dummy, placebo-controlled, multicentre study of mepolizumab adjunctive therapy in 540 subjects with severe uncontrolled refractory asthma. The primary outcome is frequency of clinically significant exacerbations of asthma over 32 weeks. Mepolizumab will be given as a 75mg IV or 100mg sc dose every 4 weeks. Inclusion criteria include regular treatment with high dose inhaled corticosteroid (ICS) over the prior 12 months prior; current treatment with an additional controller medication for ≥3 mo; eosinophilic asthma or high likelihood of eosinophilic asthma; a pre-bronchodilator FEV1 <80% for subjects ≥18 years, or <90% or FEV1:FVC ratio <0.8 for subjects 12-17 years; history ≥2 exacerbations requiring treatment with systemic CS. The study started in Oct 12 and is due to complete Mar 14 [4]. 
30/10/2012 09:09:23
NCT01691859: MEA115666: a multicentre, open-label, long term safety study of mepolizumab in asthmatic 150 subjects who participated in the MEA112997 trial. The primary outcome is frequency of AE over 48 weeks. Mepolizumab will be given as a 100mg sc dose every 4 weeks. The study started Sep 12 and is due to complete Jun 16 [4].
30/10/2012 09:09:14
Oct 12: PIII programme to evaluate the efficacy and safety of mepolizumab, as adjunctive therapy in severe uncontrolled refractory asthma to start. It includes two key studies: MEA115588: A 32-week multicentre, randomised, double-blind, double-dummy study. The primary endpoint is to evaluate the efficacy of mepolizumab 75mg IV and 100mg SC every 4 weeks vs placebo on the frequency of clinically significant exacerbations in patients with severe refractory asthma.; MEA115575: A 24-week randomised, double-blind, placebo-controlled study of mepolizumab 100mg SC adjunctive therapy every 4 weeks to reduce steroid use in patients with severe refractory asthma. The programme also includes safety extension trials that will further assess treatment of subsequent asthma attacks in mepolizumab-naive as well as previously-treated patients [3].
30/10/2012 08:42:38
Aug 12: Results of a PII study (NCT01000506) published in The Lancet 18 Aug 2012; 380:p651-9. 621 patients aged 12—74 years with a history of recurrent severe asthma exacerbations and signs of eosinophilic inflammation were randomized to one of 3 doses of IV mepolizumab (75mg, 250mg, or 750mg) or matched placebo. They received 13 infusions at 4-week intervals. 776 exacerbations were deemed to be clinically significant (primary endpoint). The rate of clinically significant exacerbations was 2.4 per patient per year in the placebo group, 1.24 in the 75mg mepolizumab group (48% reduction, 95% CI 31—61%; p<0.0001), 1.46 in the 250mg group (39% reduction, 19—54%; p=0.0005), and 1.15 in the 750mg group (52% reduction, 36—64%; p<0.0001). Three patients died during the study, but the deaths were not deemed to be related to treatment.
17/08/2012 19:52:17
In an RCT 61 non-smoking adult pts with treatment-refractory asthma, at least two exacerbations in the past year requiring corticosteroids, and proven sputum eosinophilia, were randomised to receive mepolizumab or placebo by IV infusion, monthly for a year. Primary outcome was the number of severe exacerbations per subject over the 12 month study period. There were 57 exacerbations in the mepolizumab gp and 109 in the placebo gp (2.0 vs. 3.4 mean exacerbations per subject; RR 0.57; 95% CI, 0.32 to 0.92; p=0.02). There were no significant differences in symptom scores. Mepolizumab was well tolerated. In a similar smaller 5 mth RCT (n=20) there were 12 exacerbations in the placebo gp compared to one exacerbation in the mepolizumab gp (p=0.002). Pts on mepolizumab were able to reduce their prednisone dose by 84% of their maximum possible dose vs. 48% on placebo (p=0.04) (1).
06/03/2009 10:43:59
Evidence Based Evaluations
Other  http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010834.pub2/full 
NICE scope  http://www.nice.org.uk/guidance/indevelopment/gid-tag519/documents 
NHSC/NIHR  http://www.hsc.nihr.ac.uk/topics/mepolizumab-for-severe-refractory-eosinophilic-ast/  
References  
Available only to registered users
 Category
BNF Category: Allergen Immunotherapy (03.04.02)
Pharmacology: Monoclonal antibody to interleukin-5  
Epidemiology: There were over 79,800 emergency hospital admissions for asthma in the UK in 2008/09. Of these, 30,740 were children aged 14 years or under. There were 1,131 deaths from asthma in the UK in 2009 (12 were children aged 14 years or under). An estimated 75% of admissions for asthma are avoidable and as many as 90% of the deaths from asthma are thought to be preventable [5]. Mar 14: The target population for mepolizumab is about 4% of asthma patients [8].  
Indication: Asthma 
Additional Details: severe with airway eosinophilia, and oral corticosteroid-dependent or with a history of exacerbations 
Method(s) of Administration  
Intravenous 
Subcutaneous 
Company Information
Name: GlaxoSmithKline 
US Name: GlaxoSmithKline 
Further Information
Anticipated commissioning route (England) NHSE 
High cost drug list? Yes
Tariff Not routinely commissioned by NHSE - IFR approval [12]
In NICE timetable: Yes 
When: Jul / 2016 
Note: www.nice.org.uk/guidance/indevelopment/gid-tag519 
Implications Available only to registered users