Daxas(roflumilast, 罗氟司特)用于治疗慢性阻塞性肺疾病(COPD) 。
慢性阻塞性肺疾病(COPD)是一种进行性呼吸道疾病。在气流受限影响下，COPD患者呼气期间气体过度滞留肺中，进而导致患者出现呼吸困难、运动耐量下降、生活质量恶化、死亡风险增高等危害。男性40岁以上群体中，慢性阻塞性肺疾病的发病率较高，吸烟成为主要危险因素。COPD在临床上的漏诊和误诊比例已高达70%，是当前人类的五大死因之一。
该药是一种新型的选择性磷酸二酯酶-4（PDE－4）抑制剂，每日口服1次。
罗氟司特（Roflumilast）属于磷酸二酯酶-4抑制剂，适用于慢性阻塞性肺病，商品名为Daxas。最先由德国安达（Altana）公司研制，目前已是瑞士奈科明公司（NycomedGmbH）旗下的产品。2005年，已在欧洲和美国进行了罗氟司特的临床试验。
罗氟司特为口服制剂，主要表达于与哮喘有关的炎症细胞，包括嗜酸粒细胞、中性粒细胞和肥大细胞。该药能特异地作用于参与平滑肌收缩的某种酶，从而阻断促炎症反应信号传递，具有抗炎活性，在气喘和慢阻肺的临床治疗上获得了较好的疗效。平滑肌收缩是支气管痉挛的特征之一，支气管痉挛时，气道突然狭窄，从而引起呼吸困难和呼吸系统疾病。罗氟司特还明显地延缓了呼吸系统症状的恶化提高患者的生活质量。
2009年，瑞士奈科明制药公司完成了罗氟司特的Ⅲ期临床试验后，取得了良好的结果。并在欧洲递交了上市申请，公司也计划尽快在美国申请这种药物。奈科明已与ForestLab签订合作协议，ForestLab付出6亿美元的代价，获得了在美国销售Daxas的权益，并负责罗氟司特在美国FDA审报的申请与推广销售。而奈科明将保留药物在欧洲和全球其他地区的销售权。罗氟司特作为首只磷酸二酯酶IV抑制剂，其上市将成为该类药物创新上的一大突破。
Nycomed公司2010年7月6日宣布，欧盟已批准其罗氟司特（roflumilast，Daxas）上市用于慢性阻塞性肺疾病（COPD）的治疗。本品为选择性磷酸二酯酶4（PDE4）抑制剂，是十多年来首次获得欧盟批准的新一类COPD治疗药物。
本品为一日1次用药的口服片剂，须与其他支气管扩张药合用，适用于有频繁加重病史的成人患者慢性支气管炎相关严重COPD（舒张后FEV1小于预计值的50%）的维持治疗。本品作为新一类COPD治疗药物，预计将很快投放欧洲市场，首先上市的国家为德国和英国。
4项Ⅲ期临床研究为本品获批奠定了基础。在两项关键性安慰剂对照临床研究中，共纳入超过3000例COPD患者。研究证明，本品可显著改善患者中至重度加重发作和舒张前FEV1，不管是否与长效β2激动剂联用。研究还证明，与安慰剂相比，本品可显著改善患者肺功能。
剂型及规格
片剂，0.5 mg/片。
适应症
治疗有严重慢性阻塞性肺病（COPD）伴有慢性支气管炎和加重史的患者的咳嗽及黏液过多症。
Daliresp (Roflumilast), Treatment to Reduce COPD, United States of America
Daliresp (Roflumilast) is an oral tablet that is proved to reduce the risk of exacerbations in patients suffering from severe chronic obstructive pulmonary disease (COPD). The drug has been developed by Nycomed.
Marketed as Daxas in the European markets, Daliresp was approved by the US FDA in March 2011. The European marketing approval for Daxas was received in 2010.
Daliresp will be available in US markets in the second quarter of 2011. It will be marketed by Nycomed's partner Forest Laboratories.
Chronic obstructive pulmonary disease
COPD is a progressive and irreversible lung disease which narrows the airways, thus causing respiratory problems. Breathlessness, chronic cough and congestion of phlegm in the lungs are the major symptoms associated with COPD.
These symptoms worsen further to cause exacerbation that lasts for weeks, requiring immediate hospitalisation and intensive medication. If left unattended, exacerbation can result in failure of lungs and could even be fatal.
Daliresp
Daliresp is an oral tablet to be taken once daily. It is the first and the only selective phosphodiesterase-4 (PDE4) inhibitor approved by the FDA.
Although the mechanism of action of the drug is not known, it is believed that the therapeutic action is exerted in patients by effects related to increase in intracellular cyclic adenosine metaphosphate (cAMP) in lung cells.
Clinical trials
Daliresp was eva luated in eight clinical trials conducted in a randomised double-blind, controlled parallel group. Around 9,394 patients of 40 years and above were enrolled in these trials.
Trials 1 and 2 were placebo-controlled dose selection trials of six months duration. These trials were conducted on 1,929 patients to eva luate the efficacy of Daliresp 250mcg and 500mcg tablet once daily. The median age of the enrolled patients was 63 years, associated with severe COPD in the range of 30%-80%.
Of the total randomised population, 751 patients were administered with 250mcg Daliresp and 724 with 500mcg. The 500mcg was selected over 250mcg based on the nominal improvement in lung function.
Trials 3, 4, 5 and 6 were once-year placebo-controlled trials. These were conducted to eva luate the efficacy of the treatment in patients who reported to have less than 50% of COPD severity and faced exacerbations. The enrolled patients were in the median age of 64 years.
Trials 3 and 4 included patients with less than 50% severity with chronic bronchitis and smoking history of 10 years. Trial 3 enrolled 1,176 patients of whom 567 were tested with Daliresp. Trial 4 was conducted on 1,514 patients of whom 760 were treated with Daliresp.
Both these trials failed to show significant reduction in the exacerbations in majority of the population. However, exploratory studies revealed that the treatment showed better response in reduction of COPD exacerbation in a small section of the population. Therefore further trials 5 and 6 were conducted on patients associated with chronic bronchitis, at least one COPD exacerbation in the previous year and a 20 pack year of smoking history.
Trial 5 had enrolled a total of 1,525 patients of whom 765 were administered Daliresp. Trial 6 had a total of 1,571 patients enrolled of whom 772 were tested with Daliresp. In both the trials, 500mcg Daliresp once daily confirmed that the treatment of Daliresp had resulted in a significant reduction of moderate or severe exacerbations compared to placebo. These two trials proved the safety and supported the use of Daliresp in the reduction of exacerbations of COPD.
Trials 7 and 8 were six months trails conducted to eva luate the efficacy of Daliresp as an add-on therapy to a bronchodilator. Patients enrolled for these trials were with moderate to severe COPD and of 65 years of median age.
The trials were conducted on patients with moderate to severe (40%-70% predicted) COPD without any chronic bronchitis or history of exacerbations. The results indicated that the drug showed significant response in reducing the exacerbations.