Lumacaftor/ivacaftor, a novel agent for the treatment of cystic fibrosis patients who are homozygous for the F580del CFTR mutation
Lumacaftor/ivacaftor, a novel agent for the treatment of cystic fibrosis patients who are homozygous for the F580del CFTR mutation
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DOI：
10.1080/17512433.2017.1378094
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Giovane, Richard
中科院分区：
文献类型：
--
作者：
Bulloch, Marilyn N.;Hanna, Cameron;Giovane, Richard
简介：囊性纤维化（CF）是一种常染色体隐性遗传疾病，影响全球多达90，000人。大约73%的患者是F508 del囊性纤维化跨膜传导调节因子[CFTR]突变的纯合子。传统上，治疗只包括支持性护理。因此，需要安全有效的新疗法，靶向CF的潜在分子缺陷。所涵盖的领域：2016年，美国食品药品监督管理局和欧盟委员会批准了LUM/IVA（Orkambi），这是一种CFTR调节剂，包括CFTR校正剂和增效剂，用于F508 del CFTR突变纯合子的CF患者。本文综述了LUM/IVA的药理学特征、临床疗效和安全性，并总结了LUM/IVA使用的临床前和临床数据。专家评论：LUM/IVA显示FEV 1预测值百分比（ppFEV（1））较基线有适度但显著的改善，肺部急性发作减少35%。目前，LUM/IVA是同类产品中唯一可用的口服药物，代表了CF治疗发展的里程碑。尽管如此，药物经济学数据是必要的，以证明其高成本之前，它的使用成为护理标准。
Introduction: Cystic Fibrosis (CF) is an autosomal recessive disease affecting up to 90,000 people worldwide. Approximately 73% of patients are homozygous for the F508del cystic fibrosis transmembrane conductance regulator [CFTR] mutation. Traditionally treatment has only included supportive care. Therefore, there is a need for safe and effective novel therapies targeting the underlying molecular defects seen with CF.Areas covered: In 2016, the Food and Drug Administration and the European Commission approved LUM/IVA (Orkambi), a CFTR modulator that includes both a CFTR corrector and potentiator, for CF patients homozygous for the F508del CFTR mutation. This article reviews the pharmacologic features, clinical efficacy, and safety of LUM/IVA and summarize the available pre-clinical and clinical data of LUM/IVA use.Expert commentary: LUM/IVA showed modest, but significant improvements from baseline in percent predicted FEV1 (ppFEV(1)) as well as a reduction in pulmonary exacerbations by 35% It was shown to be safe for short- and long-term use. Currently, LUM/IVA is the only oral agent in its class available and represents a milestone the development of therapies for the management of CF. Nonetheless, pharmacoeconomic data are necessary to justify its high cost before is use becomes standard of care.